Program Description


PTCOG58 celebrated the centenary of Ernest Rutherford's publication of the scientific paper confirming the discovery of the proton. The theme of the 2019 conference was innovation – scientific, clinical, technical and industrial – and how the worldwide growth of particle therapy will develop in years to come.

Objectives for the 58th annual conference were to:

  • Address individual needs in compliance with their Continuous Professional Development (CPD) plan.

  • Discuss the latest technological and clinical innovations in particle therapy.

  • Identify educational resources, networks and other for exchange of knowledge and learning about particle therapy,

  • Enhance the dialogue on clinical oncology across the NHS.

  • Discuss the current research projects within the Particle Therapy Co-Operative Group (PTCOG) and enhance opportunities for future collaboration between groups of young researchers.

  • Discuss the latest developments about practical clinical application of particle therapy.

  • Describe diagnostics and treatments in the field of particle radiation therapy.

Target Audience

Healthcare professionals who treat cancer patients using radiation therapy/particle therapy and specifically:

  • Radiation Oncologists

  • Medical Physicists

  • Dosimetrists

  • Residents

  • Radiation Therapists

Particle Therapy Cooperative Group (PTCOG) 2019 Committees , PTCOG Executive Committee

Jay Flanz, Ph.D., Chairman

Tadashi Kamada, M.D., Vice-Chairman

Marco Durante, Ph.D., Vice-Chairman

Martin Jermann, MSc, Secretary

Anita Mahajan, M.D.

James Metz, M.D., Co-Chairman of Education Subcommittee

Niek Schreuder, M.Sc. DABR, Co-Chairman of Education Subcommittee

PTCOG58 Host Committee Members

Ran Mackay, Ph.D.

Director Medical Physics & Engineering, The Christie, Manchester, UK

Karen Kirkby, Ph.D.

Professor, Richard Rose Chair in Proton Therapy, The University of Manchester, UK

Ed Smith, BM, BCh, MA

Clinical Director, Proton Beam Therapy, The Christie, Manchester, UK

James Weightman, LLM

Project Manager, Proton Therapy, The Christie NHS Foundation Trust, Manchester, UK

PTCOG58 Scientific Programme Committee

Karen Kirkby, Ph.D.

Professor, Richard Rose Chair in Proton Therapy, The University of Manchester, UK

Prof. Dr. Anthony Lomax

Chief Medical Physicist, Paul Scherrer Institute, Villigen, Switzerland

Ran Mackay, Ph.D.

Director Medical Physics & Engineering, The Christie, Manchester, UK

Anita Mahajan, M.D.

Radiation Oncologist, Brain Tumor Program, Mayo Clinic, Rochester, MN, USA

Ed Smith, BM, BCh, MA

Clinical Director, Proton Beam Therapy, The Christie, Manchester, UK

Marcelo Vazquez, M.D., Ph.D.

Associate Professor, Radiation Medicine, School of Medicine, Loma Linda University, San Bernandino, CA, USA

Poster Abstracts, Clinics: CNS, PTC58-0290

Hippocampal Sparing Radiotherapy in adults with Primary Brain Tumors: A comparative planning and dosimetric study using IMPT, IMRT and 3DCRT

P. Aka1, R. Taylor1, R. Hugtenburg2, J. Lambert3, J. Powell4

1Swansea University- South West Wales Cancer Center and the Rutherford Cancer Center, College of Medicine, Swansea, United Kingdom, 2Swansea University and South West Wales Cancer Center, College of Medicine and Medical Physics, Swansea, United Kingdom, 3Rutherford Cancer Centers, South Wales, Newport, United Kingdom, 4Velindre Cancer Center, Oncology, Cardiff, United Kingdom

Introduction: We assessed the feasibility of hippocampal sparing in adults with primary brain tumors using Intensity Modulated Proton Therapy (IMPT) and compared this with Intensity Modulated Radiotherapy (IMRT) and 3D-Conformal Radiotherapy (3DCRT).

Methods and Materials: Twenty (20) patients were identified, and each patient underwent a radiotherapy planning CT scan and 2 MRI scans. A pre-operative diagnostic MRI scan was fused with the planning CT and used for target delineation and a dedicated 3T MRI scan at the time of planning was fused with the CT for hippocampus delineation. Three hippocampal sparing plans were generated for each patient with specific prescriptions (54Gy/30 fractions, 60Gy/30 fractions and 59.4Gy/33 fractions) using IMPT, IMRT and 3DCRT. Hippocampal sparing was defined as median dose to contralateral hippocampus ≤25Gy without compromising target coverage and organ at risk dose constraints.

Results: Hippocampal sparing was achieved in 19 patients (95%) with IMPT, 16 patients (80%) with IMRT and 13 patients (65%) with 3DCRT. The largest median hippocampal dose reduction was seen with IMPT, with a mean median hippocampal dose of 4.8Gy (range:0.0Gy-24.9Gy), 14.6Gy (range:1.9Gy-21.7Gy), and 16.2Gy (range:2.3Gy-25.0Gy) for IMPT, IMRT and 3DCRT respectively. Hippocampal sparing IMPT failed in one case with the largest tumor volume (650cc) where 2/3 of the hippocampus overlapped the target volume.

Conclusion: IMPT as compared to IMRT and 3DCRT plans showed a trend towards significant and effective hippocampal sparing in adult patients with primary brain tumors. We are currently evaluating this in a larger patient cohort and comparing IMPT with VMAT.


Radiation to the olfactory structure (OS) correlates with taste/odor changes during pencil beam scanning (PBS) proton irradiation for brain tumors

T. Bevolo1, M. Gao1, V. Gondi1, W.H. Hartsell1

1Northwestern Medicine Chicago Proton Center, Radiation Oncology, Warrenville, IL USA

Purpose: Patients undergoing brain irradiation report unpleasant taste/odor changes. Leveraging the capacity of PBS to define anatomic dose delivery by treatment layer in a time-dependent manner, this study sought to correlate timing of taste/odor changes with layer-defined dose delivered to the OS and Bragg peak location relative to the OS.

Methods: Patients receiving PBS craniospinal irradiation were enrolled on a prospective trial. Over three consecutive days, patients depressed a buzzer when taste/odor was detected and again when taste/odor dissipated. Each layer was assessed for number of days overlapping the taste/odor period, which was correlated with layer-defined OS dose and Bragg peak location relative to the OS.

Results: Of 10 patients enrolled, all experienced odor changes, and 3 noted taste changes. When the taste/odor period overlapped a treatment layer for 0, 1, 2 and 3 days, mean OS dose was 0.4, 2.7, 4.9, and 16.5cGyRBE, respectively. Fit to a normal-tissue complication probability model yielded TD50 of 4cGyRBE. Number of days that layers overlapped the taste/odor period correlated with location of the OS proximal to the Bragg peak (p=0.036). The OS was located proximal to the Bragg peak on 95% of layers overlapping the taste/odor period for all 3 days and on 3% of layers that never overlapped the taste/odor period.

Conclusion: Timing of taste/odor changes during brain irradiation correlates with layer-defined dose delivered to the OS and location of the OS proximal to the Bragg peak. Radiation-induced chemosensory changes in the OS may contribute to taste/odor changes patients experience during irradiation.


Unexpected severe optic pathway toxicity in a patient with meningioma treated with pencil-beam scanning proton therapy: A case report

A. Bolsi1, J. Beer1, M.F. Belosi1, D. Siewert1, A.J. Lomax1, D.C. Weber1

1PSI Paul Scherrer Institut, Center for Proton Therapy, Villigen, Switzerland

We report on a case of a patient treated with pencil-beam-scanning proton therapy (PBS-PT) who developed severe optic pathway toxicity despite all optical structures dose constraints being within well-established limits.

The otherwise healthy 50-year-old woman was treated with definitive PBS-PT for a skull-base meningioma with no ophthalmologic impairment at treatment initiation. The treatment was delivered in a single plan using three (two quasi-lateral and a vertex) fields up to 50.4 Gy(RBE) at 1.8Gy(RBE)/fraction. Nominal doses to optical structures were below 51Gy(RBE) (D2%).

Five months after treatment, the patient presented with visual field defect on the right eye, quickly deteriorating to amaurosis, followed shortly afterwards by visual field defect on the left eye. A diagnosis of radiation-induced optic neuropathy was confirmed on MRI, which showed inflammatory changes in both chiasmatic and proximal optic nerve regions.

Consequently, a comprehensive treatment review was performed, including nominal and log-file reconstructed dose distributions, delivery accuracy, plan robustness and LET distribution. As with the nominal dose distributions, log-file reconstructed doses resulted in low-risk dose levels in the optic structures (Table 1), and MR changes were in low LET (<3KeV/μm) areas (Fig.1). Robustness analysis, including fractionation, resulted in Max/D2 doses below 54Gy(RBE) for all optical structures (Table1).

After this comprehensive review, the observed toxicity could not be correlated to any dosimetric, delivery or LET based metrics. This may demonstrate that risk of toxicity is a complex, multi-variate problem also involving patient specific factors, and not just the oft-discussed issues of end of range LET/RBE and robustness.


Does alternating wide-angle arrangement of proton therapy to skull base lesion reduce the dose to temporal lobe?

Y.J. Huang1, C.C. Huang1, P.J. Chao1

1Kaohsiung Chang Gung Memorial Hospital, Radiation Oncology, Kaohsiung, Taiwan

Bilateral opposite direction is a common treatment beam arrangement for proton therapy to a skull base lesion. It could avoid direct shooting to the brain stem and keep distal uncertainty far away from the most critical organ, which is the brain stem. However, the radiation doses in the proximal part of the proton beam are still high that makes a certain dose to bilateral temporal lobe when lateral opposite irradiation applying. Temporal lobe radiation injury may cause memory and cognitive function impairment that affect the quality of life. In this study, we evaluated the alternating wide-angle arrangement proton beams to skull base lesion in phantom to evaluate the effectiveness to sparing temporal lobe comparing to bilateral opposite direction. The alternating wide-angle proton beam angles were paired as 240-90 degrees and 120-270 degrees for treatment each day. One day treated with 240-90 degrees beams and 120-270 degrees on the other for the treatment course as following figure.

With the prescribed dose of 69.96Gy/33 Fractions to skull base lesion after optimization, the results showed that the mean doses of right temporal lobe were 41.78Gy and 39.40Gy for alternating wide-angle and bilateral opposite beam arrangements. The mean doses of left temporal lobe were 20.56Gy and 12.60Gy for alternating wide-angle and bilateral opposite beam arrangements.

Although the iso-dose coverage area of temporal lobe seems to less by alternating wide-angle proton beam arrangement in visual intuition, the alternating wide-angle proton plan did not demonstrate a numerical benefit for temporal lobe in dose volume histogram evaluation in this study.


The feasibility study of intensity-modulated proton therapy without range shifter for shallow brain tumors

C. Liu1, H. Shang2, X. Ding3, Y. Wang1

1Chinese Academy of Medical Science Shenzhen Cancer Hospital, Radiation oncology, Shenzhen, China, 2Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Shanghai, China, 3Beaumont Health System, Radiation Oncology, Royal Oak, MI, USA

Purpose: Range shifter (RS) was widely used to treat superficial tumors in proton therapy. However, the commissioning of RS requires extensive measurements and the clinical usage of RS will take extra time to set up. We aimed to explore the feasibility of intensity-modulated proton therapy (IMPT) without RS for shallow brain tumors.

Methods and Materials: The study was approved by the local ethics committee. Ten patients with brain tumors were retrospectively selected. Two IMPT plans were created for each patient: same beam angles and beam number with and without RS. Both plans were generated by delivering prescription dose (60Gy[RBE]) to clinical target volumes (CTV). 2 or 3 beam angles were selected by experienced professionals and the same beam angles were used for both plans. All the plans were normalized to have CTV D95% to the prescription dose. The dose-volume-histograms (DVH) indices for both CTV and organs at risk (OAR) were calculated to evaluate the plan quality and compared using the Wilcoxon rank sum test.

Results: Compared with the plans using RS, IMPT treatment plans using 2∼3 beams without RS achieved comparable target dose homogeneity and hot spots, brain Dmax and Dmean, brainstem Dmax, spinal cord Dmax, hippocampus Dmax, optical nerve Dmax, optical chiasm Dmax, and pituitary Dmax if at least one beam is able to cover the shallow region of the target.

Conclusions: Given appropriate beam angles and beam numbers, IMPT treatment without range shifter for shallow brain tumors is feasible.


Protonchorde: Improvement of local control in chordomas treated by proton therapy targeting hypoxic cells revealed by 18F- FAZA PET/CT tracers: preliminary results

H. Mammar1 Sébastien Froelich2, Claire Alapetite1, Stéphanie Bolle4, Valentin Calugaru1, Loic Feuvret3, Sylvie Helfre1, Laurence Champion1, Farid Goudjil1, Remi Dendal1

1Institut Curie, Oncology-Radiotherapy, Paris, France, 2Hôpital Lariboisière - APHP, Paris, France, 3Hôpital Pitié-Salpêtrière – APHP, Paris, France, 4Center Gustave Roussy, Villejuif, France

Purpose: To increase the total dose of 10% at the level of hypoxic cells only a dose of 78 GyRBE (against 70 Gy in the rest of the lesion) to improve local control at 3 years of 15% or from 71% to 86%.

Partial Results: All patients showed good tolerability. The median follow-up was 12 months (range: 3 –24). No local or distal relapse has been detected. Two patients died (#3 by pulmonary embolism and #5 by acute pancreatitis). All other patients are alive

Conclusions: Our preliminary results are very encouraging in terms of good tolerance of treatment at high doses and this thanks to metabolic imaging that allows us to study tumor heterogeneity and target the most radioresistant hypoxic cells.


Criteria for selecting patients with grade 2-3 brain tumors to proton therapy

S.A. Engelholm1, P. Munck Af Rosenschold2, I. Kristensen2, B. Smulders3, A. Muhic1, S. Alkner4, E. Jacob4, S. Engelholm4

1Rigshospitalet, Oncology, Copenhagen, Denmark, 2Skåne University Hospital, Radiation Physics, Lund, Sweden, 3Rigshospitalet, Oncology, Copenahagen, Denmark, 4Skåne University Hospital, Oncology, Lund, Sweden

Background: Region Skåne, Sweden and The Capital Region, Denmark have a collaboration concerning proton therapy (PT) at The Skandion Clinic, Uppsala. We estimated the utilization PT as a replacement to image-guided volumetric modulated arc photon radiation therapy (IG-VMAT), for low-grade brain tumors based on common criteria.

Methods: We retrospectively reviewed our records and the selection of PT patients during 2015-2018. We evaluated the dosimetric benefit for eyes, lacrimal glands, pituitary gland, hippocampi, and uninvolved brain dose was examined as part of the decision-making. The comparison of clinical alternative plans with realistic treatment planning margins based on the positioning uncertainty of the respective modalities, i.e. IG-VMAT or PT.

Results: During the period, 43 patients with intra-cranial disease were treated with PT. Children and patients with PS >2 were excluded. Selected patients for PT was brain tumors grade II-III, primarily astrocytomas and oligodengrogliomas with favorable prognostic factors. The patients had 1-6 evaluated organs at risk with lower average dose of about 5 Gy with PT, typically with a considerable reduction of the 10-30 Gy volumes. The median average dose to the brain was 4.9 Gy lower with PT compared to IG-VMAT. About forty percent of the evaluated patients were sent to PT.

Conclusions: About 40% of the evaluated patients were treated with PT. The dosimetric benefit depended on tumor location, which may translate to clinical outcomes advantage though this is at the present not clarified.

Clinics: Base of Skull, PTC58-0382

Neutron radiotherapy followed by a proton boost for locally advanced salivary gland tumors: Early clinical experience

S. Aljabab1, A. Lui2, T. Wong3, J. Liao2, G. Laramore2, U. Parvathaneni2

1Roswell Park Cancer Center, Radiation Medicine, Buffalo, NY, USA, 2Univeristy of Washington, Radiation Oncology, Seattle, WA, USA, 3Seattle Cancer Care Alliance- Proton Therapy Center, Radiation Oncology, Seattle, WA, USA

Purpose: Despite improvements in local control with neutron therapy in salivary gland tumors, caution is required near vital CNS structures. A mixed neutron and proton boost approach can potentially maximize local control while minimizing toxicity. We report our early clinical experience.

Materials and Methods: From 2014 to 2018 we retrospectively reviewed 29 patients with locally advanced salivary gland tumors. Median age was 56 years, patients had ACC histology (79%), T4 disease (86%) skull base invasion (86%) and orbital invasion (31%). Five patients had prior radiation. Fifteen patients (51.7%) had pre-RT resection of which only 2 were GTR with negative margins. Median neutron dose was 18.4 Gray (Gy). Proton boost dose ranged from 16 to 45 Gy (RBE). Toxicity was graded as per CTCAE v4.03.

Results: At a median follow up of 15.4 months (IQR, 5.8-24.1), locoregional recurrence occurred in 4 patients, distant recurrence in 2 patients and death in 2 patients. The 2-year actuarial locoregional control, progression free survival and overall survival were 93.1%, 89.7% and 96.6% respectively. Excluding re-irradiated patients, common recorded acute grade 3 toxicities were mucositis (50%) and dermatitis (37.5%). There were no documented acute grade 4 or 5 toxicities. Late Grade 3/4 late include trismus (4%), hearing loss (8.3%) and expected visual loss (25%). Radiation necrosis of the bone occurred in 2 patients and the brain in 2 patients.

Conclusion: In this challenging cohort of patients, early outcomes for this novel approach are promising and compares favorably with our historical experience with NRT alone.


Proton therapy versus volumetric modulated arc therapy for benign tumors of the skull base and sellar location

M. Kharouta1, R. Pidikiti1, F. Jesseph1, M. Smith1, D. Dobbins1, D. Mattson1, S. Choi1, D. Mansur1, M. Machtay1, A. Bhatt1

1University Hospitals/Seidman Cancer Center at Case Western Reserve University, Radiation Oncology, Cleveland, OH, USA

Background: The skull base and sella are surrounded by critical neural organs at risk and thus minimizing the integral dose while treating tumors in this location is advantageous. Our aim is to evaluate the dosimetric differences of volumetric modulated arc therapy (VMAT) as compared to 3-D proton therapy (PBT).

Methods: Ten patients with pituitary adenomas (N=5) and skull base meningiomas (N=5) who were treated with PBT and had a comparison VMAT plan available were evaluated. The average mean and maximum doses to the bilateral optic structures, cochlea, and nearby brain were compared across treatment modalities using a paired Student's T-test, with use of the Bonferroni correction for multiple comparisons.

Results: Median dose was 50.4 CGE (45-52.2). Target volume coverage was comparable in both proton and VMAT plans for all cases. Compared to VMAT, PBT plans showed a significant reduction in mean and maximum doses to the right lens and eye, with a trend towards a significant reduction for the mean dose to the right optic nerve. Doses to other structures were comparable between plans, with a trend towards lower doses for proton plans.

Conclusions: PBT as compared to VMAT resulted in meaningful dose reductions to organs at risk while maintaining comparable target coverage. Further refinements in proton therapy including intensity modulation may have the potential to further minimize dose to critical neural structures in the skull base and sellar location.


Use of optical coherence tomography (OCT) as routine base line examination in meningioma patients before proton beam radiation

C. Lütgendorf-Caucig1, R. Dunavölgyi2, P. Georg1, A. Perpar1, C. Fussl1, R. Konstantinovic1, M. Ulrike1, F. Piero1, H. Eugen1

1MedAustron, Radiation Oncology, Wiener Neustadt, Austria, 2Medical University of Vienna, Department of Ophthalmology, Vienna, Austria

Introduction: The assessment of visual field (VF) measured via automatic perimetry (AP) is a standard examination. Optical coherence tomography (OCT) is a non-invasive, non-contact and painless imaging technique that provides high-resolution measurements and cross-sectional imaging of the retina and retinal nerve fibre layer (RNFL). The RNFL thickness is of particular interest in clinically manifest as well as subclinical optic neuropathies.

Methods: Visual parameters including VF and RNFL thickness were measured before start of radiation. VF was measured by AP, RNFL via OCT. The examination was performed prior to treatment planning for proton therapy. Additionally, the involvement of the anterior visual pathway (optic nerve, chiasma) was defined on the planning MRI.

Results: Twenty-four patients with no ophthalmologic comorbidities were included. The mean age at time of radiation was 55.4 a (+/- 12.8 a). At baseline a restriction of the VF was detected via AP in 12 patients on the left and in 7 patients on the right. Via OCT in 13 patients a deficiency was detected on the right side and in 9 patients on the left. On MRI the right optic nerve was in direct contact to the meningioma in 13 patients, the left optic nerve in 16 and the chiasma in 11 patients, respectively.

Discussion: In this cohort the detection of the anterior visual pathway disorders was higher with OCT compared to AP. OCT provides additional base line information which is beneficial for treatment planning, follow-up and as endpoint in future clinical trials.


A new combined proton-photon strategy for dose escalation in clivus chordoma irradiation

M. Vidal1, A. Gerard1, C. Barnel1, D. Maneval1, J. Herault1, A. Claren1, J. Doyen1

1Center Antoine Lacassagne, Institut Méditerranéen de Protonthérapie, Nice, France

This work describes new irradiation strategies to reach therapeutic dose (72-74GyE) in clivus chordoma - a challenge because of OAR proximity that often leads to tumor undercoverage.

For 10 patients, sequential boost plans were computed with proton SFUD and IMPT with 50.4 GyE (1.8GyE/fraction) delivered to the Low Risk CTV (LRCTV) and 23.4 GyE to the High Risk CTV (HRCTV). Simulated Integrated Boost (SIB) plans were also computed with both SFUD and IMPT to deliver 73.5 GyE (2.1 GyE/fraction) to the HRCTV, the LRCTV receiving 56 GyE (1.6 GyE/fraction). A new combined proton-photon strategy consists in irradiating LRCTV with proton SFUD or IMPT (50.4 Gy) with Stereotactic Body Radiotherapy (SBRT) to add 22 Gy RBE (2GyE/fraction) to the HRCTV.

Proton plans were computed with RayStation 6.0 (RaySearch Laboratories, Sweden) with a CTV-based robust optimization (3% of the range for range uncertainties and 3mm for metric uncertainties). SBRT treatments were planned with Cyberknife® on Multiplan 5.3 (Accuray, USA).

OAR dose constraints were evaluated following the ICRU91 and ICRU78 recommendations for SBRT and protons plans respectively. All plans are clinically deliverable and respect the OAR constraints – differences between the plans are about tumor coverage, conformality and homogeneity. Figure 1 shows clearly that in average, IMPT-SIB achieved the best tumor coverage for LRCTV and HRCTV for protons-only plans. However, the best tumor coverage for both volumes was reached for the combined proton-photon technique including SBRT. An example of isodosis obtained for 3 different techniques is shown for one patient in Figure 2.

Clinics: Eye, PTC58-0684

Outcome and visual prognosis on a series of patients, stage T1 post choroidal melanoma treated with proton therapy at ICPO

R. Dendale1, A. Toutee2, I. Pasquie1, F. Goudjil1, L. Lumbroso Lerouic2, C. Levy2, H. Mammar1, L. Desjardins2, N. Cassoux2

1CPO - Institut Curie, Radiation oncology, Orsay, France, 2Institut Curie, Ophthalmology, Paris, France

Method: Between 11/91 to 12/10, 8399 patients treated for a choroidal melanoma were recorded in the Institut Curie database. Among them, all patients with stage T1 choroidal melanoma treated with proton irradiation and with a minimal follow up of 5 years, were selected. They were divided in two groups depending on the distance between Tumor and Macula or Papilla (T-M/P). Group 1: T-M/P > 3 mm and Group 2: T-M/P < 3 mm. Survival and functional impact on vision were analyzed.

Results: Four hundred twenty-four patients were selected. The Gender Ratio (F/M) was 51.9%/48,1%, The mean age was 56,2 Years (5,1– 23). The median follow up: was 10,5yrs ((5,1 – 23). Local recurrence rate was 0%. Overall survival rate was 91,7 % at 10 yrs IC 95% [88,6% - 94,9%]. Initial Visual acuity (VA): Group 1 > Group 2. At last f-up, VA: Group 1 > Groupe 2 (p=0,03). Impact of proton therapy on VA score was related to the distance between tumor border and macula or papilla limits. At last follow up 70% of pts from Group1 had VA ≥ 20/40 and 50% of pts from Group2 had a VA > 20/200.

Conclusion: This analysis of a series on selected patients with T1 posterior choroidal melanoma with a long follow up shows excellent local and overall survival rates, and significant visual function conservation depending on the distance between the tumor and the macula / papilla.


Preclinical commissioning of a new eye tracker device in CNAO

G. Elisei1, A. Pella1, G. Calvi2, R. Ricotti1, B. Tagaste1, F. Valvo3, M. Ciocca4, R. Via5, E. Mastella4, G. Baroni1,6

1Centro Nazionale di Adroterapia Oncologica CNAO, Clinical Department - Bioengineering unit, Pavia, Italy, 2Centro Nazionale di Adroterapia Oncologica CNAO, Technical Department, Pavia, Italy, 3Centro Nazionale di Adroterapia Oncologica CNAO, Clinical Department - Radiotherapy unit, Pavia, Italy, 4Centro Nazionale di Adroterapia Oncologica CNAO, Clinical Department - Medical Physics unit, Pavia, Italy, 5Paul Scherrer Institute, Bioengineering Department, Villigen, Switzerland, 6Politecnico di Milano, Department of Electronics Information and Bioengineering, Milano, Italy

An Eye Tracking System (ETS) is used at CNAO for providing a stable and reproducible optical proton therapy (OPT) setup, featuring a fixation light (FL) and monitoring stereo-cameras embedded in a rigid case. The ETS is mounted on industrial robots to accurately position the FL according to patient-specific gaze direction (polar/azimuth) established during treatment planning (Eclipse, Varian).

An upgraded ETS is proposed for an improved clinical workflow standardization and simplification. We discuss these hardware and software updated and their pre-clinical commissioning.

The revised ETS design operates with the main systems already in use at CNAO featuring reduced dimension since part of the electronics is moved out of the device (Figure 1, panel a). The use of a single cable and standard connectors for signals improved the device connectivity. The visibility of the FL is improved due to tunable LED intensity.

An ETS setup simulator algorithm is developed to automatically provide the FL positioning in space avoiding interferences with patient, beam and other hardware (Figure 1, panel b). Algorithm validation was performed simulating ETS setup of 30 patients already treated at CNAO.

Differences between the position of ETS reference points estimated by the algorithm and those measured by the in-room imaging system are presented in Fugure2. The corresponding deviation of the gaze direction is on average 0.17°polar and 0.60°azimuth.

A more reliable hardware-software package for OPT has been presented ensuring ETS positioning with an average accuracy of 1.5 mm corresponding to deviation of gaze direction lower than 1°.


Commissioning of eye treatment with rotating gantry and energy scanning carbon-ion beam

N. Saotome1, S. Yonai2, H. Makishima3, Y. Hara2, T. Inaniwa2, M. Sakama1, N. Kanematsu1, H. Tsuji3, T. Furukawa2, T. Shirai2

1National Institute of Radiological Sciences, Medical Physics Section, Chiba, Japan, 2National Institute of Radiological Sciences, Department of Accelerator and Medical Physics, Chiba, Japan, 3National Institute of Radiological Sciences, Hospital, Chiba, Japan

At the Heavy Ion Medical Accelerator in Chiba (HIMAC), more than 200 ocular melanoma patients have been successfully treated by carbon-ion beams since 2001. Traditionally, the vertical and horizontal port with the passive beam delivery system were used to irradiate target volume. To evaluate the advantage of use of rotating gantry and energy scanning carbon-ion beams for choroidal malignant melanoma, we have started the commissioning of the treatment from 2017. The treatment techniques are mostly the same as generally used in HIMAC except for the suturing titanium clips to the outer sclera surface for target positioning. To make the effective dose calculation possible using treatment planning system (TPS), computed tomography (CT)-based treatment planning is employed. By evaluation of the dose distribution, energy scanning with rotating gantry showed to be equal to superior compared to traditional passive scattering method. An evaluation of dose calculation and beam delivery accuracy has proven that the ocular melanoma treatment with rotating gantry and energy scanning carbon-ion beam was feasible.


A prospective international Survey on Ophthalmic Radiation Therapy Toxicity (SORTT)

W. Sauerwein1,2, P.T. Finger3, B. Gallie4,5, Y. Gavrylyuk6

1University Hospital Essen, NCTeam- Department of Radiation Oncology, Essen, Germany, 2Okayama University, Neutron Therapy Research Center, Okayama, Japan, 3The New York Eye Cancer Center, Ophthalmology, New York, NY, USA, 4Princess Margaret Cancer Center, Ophthalmology, Toronto, Canada, 5University of Toronto, Medical Faculty, Toronto, Canada, 6Princess Margaret Cancer Center, IT Department, Toronto, Canada

Purpose: Radiation plays an important role in the treatment of ophthalmic malignancies. Though many different radiation modalities (i.e. protons and brachytherapy) can be used to destroy ocular tumors, each varies in the irradiated volume. Therefore, we can expect a difference in the incidence and location of side effects as well as in functional outcomes. However, there are only strikingly few comparative studies or staging systems available to collect the incidence and impact of ophthalmic radiation.

Methods: After plenary meetings during the Eye Cancer Working Days in Paris and Sydney, a prospective international survey was started. Ophthalmic and radiation related data fields were fashioned collecting both treatment and outcomes. Patient privacy and ethics protections were incorporated into an internet-based registry to prospectively track outcomes for patients after ophthalmic radiation therapy. These include brachytherapy as well as external beam radiotherapy with protons and photons. After an initial year-long enrollment period, patients will be followed for at least 3 additional years.

Results: Twenty-one centers from 6 continents agreed to join this prospective registry. They are currently obtaining local IRB and ethics approvals. Patient accrual has been launched on January 1, 2019.

Conclusions: This database will support the creation of a dedicated ophthalmic radiation side effects grading system, and accumulate evidence about risks associated with currently used ophthalmic radiation modalities. Such data may lead to preferred radiation practice patterns and staging systems in treatment of ocular tumors. We hope this study will lead to improved local control and less toxicity among ocular tumor patients.


Surgery and proton therapy of conjunctival melanomas

J. Thariat1, J. Salleron2, C. Maschi3, E. Fevrier3, A. Claren4, J. Herault4, J.P. Caujolle3

1Center Baclesse / ARCHADE, Radiation Oncology, Caen, France, 2Cav, Statistics, Nancy, France, 3Chu, Ophthalmology, Nice, France, 4Cal, Radiation Oncology, Nice, France

Introduction: Conservative strategies of conjunctival melanomas include no touch surgery and adjuvant treatments including cryotherapy, mitomycin and radiation therapy. Outcomes after postoperative proton therapy are reported.

Material and Methods: Monocentric retrospective study of consecutive patients treated between 1992 and 2018.

Results: Characteristics of 92 patients were age 63yo, male 55%, de novo 21%, nevus 14%, melanosis 65%, T1 71%, T2 15%, T3 14%, unifocal 83%, peribulbar 85%, > 90 degrees 69%, epithelioid 40%, thickness 2.5mm [1.0-4.0], diameter 7.0mm [4.5-10.0], incomplete resection 58%, ulceration 15%. Median follow-up was 2.7 years. Five-year local failure rate was 33%. Of 25 local recurrences, 52% were marginal/out-of-field, 20% in-field, 28% unspecified. First surgery at expert center resulted in 19% (vs not: 34%) local relapses, p=0.16, with salvage exenteration in 14 patients. Tumor stage, angular involvement were significant factors for local relapse. Five-year progression-free survival and cause-specific death rates were 62% and 4%. Clinical stage and epithelioid type were prognostic factors for poorer progression-free survival. Grade 3 trophic toxicity occurred in 22.9% of patients and was treated locally, with grafts in 14% of cases. Hypertonia occurred in 14%, cataract in 22. Visual acuity, assessed in 61 patients, was stable/improved in 57%. Prognostic factors for visual deterioration were age, tumor extent (multifocality, angular involvement > 180 degrees) and cryotherapy.

Conclusions: 5y local failure rate after postoperative proton therapy was 33% with most failures being out-of-field and resulted 15% non-conservative salvage treatments. Mitomycin was not associated with improved local control. Toxicities were overall manageable.


Use of a compensator in proton therapy for large conjunctival melanomas

P. Hofverberg1, G. Angellier1, A. Gerard1, M.L. Peyrichon1, A. Claren1, J. Herault1, J. Thariat2

1Center Lacassagne, Radiation Oncology, Nice, France, 2Center Baclesse / ARCHADE, Radiation Oncology, Caen, France

Introduction: Adding a compensator to the postoperative proton therapy of conjunctival melanomas can reduce irradiated ocular volumes and may reduce toxicities in case of large surface tumors. With the use of mitomycin, smaller prophylactic volumes are irradiated. However, most local failures occur out-of-field (see clinical abstract). We assessed toxicities depending on the use of a compensator.

Materials and Methods: In this retrospective study, consecutive conjunctival melanomas patients were treated from 1992-2017. The use of a compensator was associated with tissue gel equivalent bolus. Lid retraction was performed if conjunctival fold were not involved, involvement requiring the use of a compensator.

Results: Of 66 patients, age 63, over 90° involvement N=44, PAM N=37, 40 had a compensator. Use of a compensator was highly correlated with large tumor surface (p<0.001) and inversely corelated with mitomycin (p=0.002). Larger volumes of surface structures (corneal/conjunctiva/eyeball) were irradiated with the use of a compensator, again corelated with tumor surface, suggesting that tumor coverage was maintained for large surface tumors. Surface structure complications were borderline significantly with the use of a compensator (53 vs 93%,p=0.065). The lens was significantly less irradiated with a compensator (p<0.001).

Conclusion: With the use of a compensator, which is highly correlates with large tumor surface, toxicities were manageable. Data on lid toxicity will be presented at PTCOG2019. Propensity score matching on the surface involved and local control will be assessed to account for a possible increase in EBR using a compensator (resulting in end of SOBP at the ocular surface)

Clinics: Pediatrics, PTC58-0504

The impact of a proton therapy facility on radiotherapy practice patterns at a children's hospital

J. Breneman1, H. Esslinger2, L. Pater3, R. Vatner4

1Cincinnati Children's Hospital/University of Cincinnati, Radiation Oncology, Cincinnati, OH, USA, 2University of Cincinnati, Radiation Oncology, Cincinnati, OH, USA, 3University of Cincinnati/Cincinnati Children's, Radiation Oncology, Cincinnati, OH, USA, 4University of Cincinnati/Cincinnati Children's, Radiation Oncology, Cincinnati, OH, USA

Introduction: In October 2016, Cincinnati Children's Hospital (CCHMC) opened a proton therapy center. We report the impact of this center on the volume and type of radiotherapy delivered for patients served by CCHMC.

Methods and Materials: Records for CCHMC patients treated in the 12 months prior to, and 24 months following the opening of the proton center were analyzed for distribution of diagnoses, treatment modality, treatment intent and referral source.

Results: In the 12 months prior to opening the proton center, 93 unique patients received 103 courses of photons. In the 12 months following opening of the center, 142 patients received 151 courses of radiotherapy – 52% with protons. In the second 12 months following opening, 160 patients received 180 courses of radiotherapy – 56% with protons. Prior to protons, 72% of treatment courses were considered definitive, with 86% categorized as definitive after protons were introduced. Most patients with solid tumors are now treated with protons (Figure 1). Prior to the proton center, 5 patients (5%) were directly referred from outside institutions. In the one- and two-year periods following protons, 36 (25%) and 40 (25%) patients were direct outside referrals for radiotherapy – most often for sarcomas or CNS tumors (Figure 2).

Conclusions: Opening a proton center at a children's hospital had a significant impact on the number of patients and diagnoses treated with radiotherapy. These data can inform new centers in resource allocation needed for potential changes in patient population.


Particle versus photon radiotherapy impact on toxicity in children: Which evidences?

J.L. Habrand1, D. Stefan1, J. Thariat1, P. Lesueur1, W. Kao1, A. Véla2, J. Geffrelot1, T. Tessonnier2, J. Balosso1, M.A. Mahé3

1CLCC François Baclesse, Radiotherapy, Caen, France, 2CLCC François Baclesse, Medical Physics, Caen, France, 3CLCC François Baclesse, Hospital Board, Caen, France

Objective: Evaluating the place of particle therapy (PT), from a literature review on toxicity.

Methods: Publications dating from 1997-2017 (pub) were retrieved from Medline. Dosimetric investigations (group 1), secondary cancers predictive models (K2: group 2), and clinical series (group 3) were evaluated and focused on inter-comparisons between PT and XR (3D/IMXRT photons), on 16 toxicity items, along with significance (pS if >.05).

Results: One hundred sixty-three (163) articles were selected, with 145 evaluable (54 pre-clinical and 91 clinical) including 40 (27 pre-clinical and 13 clinical) inter-comparing PT and XR for toxicity (as single or multiple events):

  • Group 1 pub (349 analyzed children): 14 CNS, 3 head and neck (HN), 3 thorax, 4 pelvis and abdomen

  • Group 2 pub (= 126 children): 15

  • Group 3 pub (= 1249 children): 4 CNS, 1 HN, 3 endocrine, 1 lung, and 3 acute tolerance


  • Group 1: P>XR with pS in 8/10 brain, 6/10 cochlea, 4/8 endocrine, 2/3 visual, 2/3 bone, 4/4 heart, 3 /4 digestive tract (pancreas conflicting), 2/2 lung, 2/2 breast, 1/6 cognition+IQ. P≤XR: 0.

  • Group 2: P>XR with pS: 7/22. P≤XR: 0.

  • Group 3: P>XR with pS: 1/1 brain, 2/2 cognition+IQ (schooling contradictory), 2/3 endocrine, 2/3 acute. P<XR with pS: 1/1 lung, 1/1 salivary.

Conclusion: All groups 1+2 and most group 3 evidenced the superiority of PT, although pS value was not systematically quoted. No clinical intercomparison was randomized. If CNS seems well documented, schooling performances are still debatable and other sites are poorly documented, or controversial, such as lungs and pancreas.


The dosimetric significance of Pencil-Beam-Scanning-Proton-Beam-Therapy lateral penumbra on the vertebrae superior and inferior to the treatment field in paediatric radiotherapy

P.S. Lim1,2, V. Rompokos3, Y.C. Chang2, G. Royle4, M. Gaze2, J. Gains2

1Paul Scherrer Institut, Center for Proton Therapy, Villigen, Switzerland, 2University College London Hospitals, Department of Clinical Oncology, London, United Kingdom, 3University College London Hospitals, Department of Radiotherapy Physics, London, United Kingdom, 4University College London, Medical Physics and Biomedical Engineering, London, United Kingdom

Background: Partial irradiation of the vertebrae in children may lead to future growth asymmetry. Therefore, any adjacent vertebra unable to be adequately spared from radiation is usually included. This work evaluates the lateral penumbra of Pencil-Beam-Scanning-Proton-Beam-Therapy (PBS-PBT) compared with Intensity-Modulated-Arc-Therapy (IMAT) and its dosimetric impact on the vertebrae within and at the edge of the treatment field.

Methods: Twenty pediatric abdominal neuroblastoma cases were double-planned using PBS-PBT and IMAT to 21Gy in 14 fractions, optimized to produce a rapid dose fall-off at the superior and inferior vertebrae. All PBS-PBT plans required a 5cm range-shifter. The lateral penumbra was measured as the 20%-80% isodose distance in the cranio-caudal direction along the anterior vertebral body. Dose to the superior/inferior (n=39) and adjacent (n=20) vertebrae were analyzed.

Results: The lateral penumbra was larger with PBS-PBT than VMAT by 2.8mm (median 8.9mm vs. 6.1mm,p=0.0001). There was no statistically significant difference between both plans for superior/inferior vertebrae V20Gy,V10Gy,mean dose,D50% or D2%. There was marginally lower superior/inferior vertebra D95% coverage with PBS-PBT than VMAT (median 0.71Gy vs 1.79Gy,p=0.000). However, this was appropriately reflected in the reduced dose coverage to the adjacent vertebrae with PBS-PBT V20Gy (median 95.3% vs 99.7%,p=0.001) and D95% (median 20.1Gy vs. 20.6Gy,p=0.001).

Conclusion: These results suggest that the slight differences were likely due to inter-planner variability on the position chosen to optimise dose fall-off rather than an effect from increased PBS-PBT lateral penumbra. As these values were within accepted range clinically, we conclude that the increased PBS-PBT lateral penumbra has a minimal impact on vertebral dosimetry.


Monitoring and management of anatomical variations during proton therapy treatments in pediatric patients

S. Vennarini1, F. Francesco1, B. Rombi1, M. Amichetti1, M. Schwarz1, S. Lorentini1

1Protontherapy Center, Apss, Trento, Italy

Introduction: Proton therapy (PT) is increasingly being used for pediatric tumors. This is mainly due to the advantages with respect to conventional therapy in terms of organs at risks (OAR) sparing. It is known that PT is more sensitive to anatomical/density modifications. Aim of this study is to present our experience in monitoring and managing anatomical variations in cranial and spinal pediatric lesions.

Materials and Methods: Five cases, with different histology and location, were studied:1 Skull base chordoma, 1 supratentorial glial neoplasm with hygroma, 1 craniopharyngioma with cystic component, 1 glial tumor of the posterior cranial fossa with vermian residue and 1 atypical meningioma with residual disease in close proximity with the cervical cord. Each patient underwent several CT and MR scans over the treatment course. The following MR sequences were acquired: T2 (study of the cystic and hygromatous component), 3D Flair (study of the edemigenous component), 3D T1 (OAR anatomical definition), DWI (study of cellularity).MR imaging was used to outline target and OAR on the control CTs, then the nominal plan was re-calculated on the CT. In case of target under dosage or OAR constraints violation a re-planning occurred in order to recover the initial dose prescription/constraints.

Results: A total of 9 CT and 15 MR were acquired in this study. Only in 1 case the re-planning was needed due to the increase of the cystic component in a craniopharyngioma.

Conclusions: Monitoring and management of anatomical variations via repeat imaging is feasible in pediatric patients and in some cases, it was used to trigger replanning.


Utilising national data in health service research for proton therapy: A paediatric example

T. Mee1,2, N.G. Burnet1,2, A. Crellin3, N.F. Kirkby1,2, E. Smith1,4, K.J. Kirkby1,2

1University of Manchester, Division of Cancer Sciences, Manchester, United Kingdom, 2The Christie NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, United Kingdom, 3Leeds Teaching Hospitals NHS Trust, Leeds Cancer Center, Leeds, United Kingdom, 4The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom

Purpose: Data plays a key role in service planning and health service research. Although there is a limited quantity of proton therapy (PBT) data available, there is a wealth of incidence and conventional radiotherapy (CRT) data. We investigate how Public Health England (PHE) pediatric incidence and CRT can be used to inform the national proton therapy (PBT) service by looking at variations across England.

Methods: PBT-relevant incidence data (patient, tumor, geographical event information) was obtained from PHE, excluding NHS Proton Overseas Programme (POP) activity. Paediatric incidences (age<16) were extracted. The data was geographically grouped by clinical network (CN). Age-standardised rates (ASR) for CNs were calculated as incidences per 100k under-16 population. Conventional RT utilization (CRTU) divides the number of incidences with an RT record by the total number of incidences. The results were used to create heat-maps for England.

Results: Figure 1 displays the CN heat-map for ASR and Figure 2 the CRTU heat-map. There are clear variations in incidence rates between CNs. Wessex has the highest ASR (20.5 incidence per 100k) and East-Midlands the lowest (16.7 incidence per 100k). There is also variation in CRTU across England. Thames valley has the lowest CRTU in pediatric incidences of relevance to PBT, with only 20% receiving CRT, while Northern England has the highest with 37.7%.

Conclusions: National cancer data has increased in quality and granular data can assist in PBT health service research. This data can estimate additional referral numbers or potential current under-referral numbers and ensure equity of access.


Proton beam therapy in pediatric patients with brain tumors

B. Rombi1, S. Vennarini1, M. Roggio2, M. Buwenge3, F. Melchionda4, I. Ammendolia3, L. Ronchi3, S. Cammelli3, A.G. Morganti3, M. Amichetti1

1Protontherapy Center, Oncology Department, Trento, Italy, 2Medicine faculty, University of Ferrara, Ferrara, Italy, 3Radiation Oncology Center, Dept. of Experimental- Diagnostic and Specialty Medicine – DIMES- University of Bologna, Bologna, Italy, 4University of Bologna, Department of Pediatrics, Bologna, Italy

Purpose/Objective: We report a collaboration experience between two institutions and clinical outcomes in proton-beam-therapy (PBT) of pediatric brain tumors.

Material and Methods: From November 2015 to January 2019, 13 consecutive patients (Male/Female: 9/4; median age 5 years [range 1-17]) with brain tumors were treated with PBT. Five patients had Medulloblastoma (one standard risk), 2 Pylocitic Astrocytoma, 1 Pituitary Germinoma, 1 parietal Choroid Plexus carcinoma, 1 grade II Meningioma of the interpeduncolar cistern contiguous at III cranic nerve, 1 Pituitary retrochiasmatic Craniopharyngioma, 2 Atypical theratoid rhabdoid tumors. Eleven patients underwent surgery before PBT (partial resection: 6, subtotal resection: 4, gross total resection: 1). Various chemotherapy regimens were received by 11 patients following specific clinical protocol. Toxicity was scored using the Common Terminology Criteria for Adverse Events Version 4.0. Median total delivered PBT dose was 54 Gy RBE in 1.8 daily fractionation. Nine patients received daily anesthesia during radiotherapy course.

Results: The therapy was completed by all patients and was well tolerated without interruptions. With a median follow-up of 17 months [range: 8-38] all patients are alive. Twelve patients are in complete remission/stable disease, one in progression. Grade 3 acute toxicity of neutropenia and fatigue were experienced by 3 patients. Two patients experienced late toxicity: one had intracranial bleeding self-solved and one developed asymptomatic cavernoma.

Conclusion: Our experience has shown the good tolerability of PBT. Efforts to reduce complications are warranted. Further follow-up will allow to better evaluate long-term sequelae.


What is the clinical outcome of proton beam therapy for pediatric patients with medulloblastoma in Korea?

S.H. Youn1, J.Y. Kim1, H.J. Park2, S.H. Shin3, S.H. Lee4, E.K. Hong5

1National Cancer Center- Korea, Proton Therapy Center, Goyang-si, Korea Republic of, 2National Cancer Center- Korea, Department of Pediatrics, Goyang-si, Korea Republic of, 3National Cancer Center- Korea, Neuro-Oncology Clinic, Goyang-si, Korea Republic of, 4National Cancer Center- Korea, Department of Radiology, Goyang-si, Korea Republic of, 5National Cancer Center- Korea, Department of Pathology, Goyang-si, Korea Republic of

Purpose: To evaluate clinical outcome of pediatric patients with medulloblastoma treated with proton beam therapy (PBT) at National Cancer Center (NCC), Korea.

Methods: Thirty-six pediatric medulloblastoma patients treated with PBT between July 2004 and December 2015 at NCC, Korea were retrospectively analyzed. Thirty-two patients treated with curative aim were included, and 4 re-irradiated cases were excluded. We calculated overall survival (OS) and progression-free survival (PFS) rate and reviewed treatment-related acute toxicities.

Results: The median follow-up duration was 49months (range, 7-113). The median age at PBT was 7(range, 2-20). Twenty-six patients were high-risk (HR) cases. Most (except 2) received craniospinal irradiation (CSI) with median CSI dose of 36.0Gy(range, 23.4-39.6) and median total dose of 55.8Gy(range, 32.4-61.2). The median interval from operation to PBT was 37days (range, 21-845). Ten patients showed disease relapse, among them 5 patients dead at the time of analysis. The 3-year OS and PFS for all were 87.3%, and 71.6%. The 3-year OS and PFS of HR were 84.3% and 65.0%; 88.2% and 65.8% for M+stage, 90.5% and 66.7% for residual-disease>1.5cm3, and 71.4% and 57.1% for ≤3years, respectively. There was minimal treatment gap during PBT, the median PBT duration being 46days (range, 33-52). Concomitant chemotherapy was used in 14 patients in HR, and they showed higher acute toxicities compared to the patients without concomitant chemotherapy.

Conclusions: The patients referred to NCC, Korea for PBT were mostly HR patients. Although the treatment referral was mostly from outside the hospital, treatment interval and duration were kept optimal. The clinical outcome was reasonably good considering the advanced nature of disease.

Clinics: Breast, PTC58-0706

Cardiac and lung sparing in breast radiotherapy, proton and photon planning study with free (FB) and breath hold (BH) technique

K. Czerska1, P. Winczura2, J. Wejs-Maternik2, A. Blukis2, M. Antonowicz-Szydlowska2, A. Rucinski3, P. Olko3, A. Badzio2, R. Kopec1

1Institute of Nuclear Physics PAN, Cyclotron Center Bronowice, Krakow, Poland, 2Radiotherapy Center Elblag, Radiotherapy, Elblag, Poland, 3Institute of Nuclear Physics PAN, Proton Radiotherapy Group, Krakow, Poland

Purpose: Proton therapy of left sided breast cancer can be advantageous in comparison to photon treatment in terms of cardiac sparing. The choice of FB or BH technique depends on the anatomy of patient. Main goal of this study was to assess the benefit from using breath hold or proton therapy in early breast cancer adjuvant radiotherapy.

Materials and Methods: The data form six breast cancer patients were used to prepare treatment plans with photons and protons (on both: FB and BH). Photon plans included tangential fields, while proton plans contained fields from anterior-oblique direction. Prescribed dose for those plans was 50 Gy or 50 Gy(RBE) in 25 fractions. All plans fulfilled dose distribution criteria in the PTV and optimal sparing of the heart, left anterior descending artery (LAD) and lungs was attempted. Statistical tests were used for dosimetric comparison of all plans.

Results: We found that in proton plans mean dose to the heart, LAD and lung was significantly reduced, at least by a factor of 2. Results are presented in the table 1.

Conclusions: The proximity of the heart and LAD to the target makes the irradiation of the left-sided breast challenging. These results show that proton technique could lead to promising cardiac and lung sparing, especially when BH treatment with photons is not possible or in patients with significant cardiac comorbidities. We did not reveal further dose reduction in protons while using breath hold, as it is in the case of a photon technique.


Critical appraisal of the potential role of IMPT for advanced breast cancer

D. Franceschini1, L. Cozzi1,2, F. De Rose1, I. Meattini3, A. Fogliata1, S. Cozzi1, C. Becherini3, S. Tomatis1, L. Livi3, M. Scorsetti1,2

1Humanitas Research Hospital and Cancer Center, Radiotherapy and Radiosurgery, Milan, Italy, 2Humanitas University, Biomedical Sciences, Milan, Italy, 3Azienda Ospedaliero-Universitaria Careggi- University of Florence, Radiation Oncology Unit- Oncology Department, Florence, Italy

Purpose: To investigate the role of intensity modulated proton therapy (IMPT) for advanced breast carcinoma in comparison with volumetric modulated arc therapy (VMAT).

Methods: A cohort of 20 patients (10 breast-conserving and 10 post-mastectomy patients, the latter with tissue expander implants) was retrospectively planned for locoregional treatment using VMAT and IMPT. Proton plans were computed with or without robust optimization methods. Plan quality was assessed by means of quantitative analysis of the dose volume histograms and scored with conventional metrics. In addition, estimates of the risk of secondary cancer induction (excess absolute risk, EAR) were performed according to a model inclusive of fractionation, repopulation and repair.

Results: Concerning target coverage, the data proved a substantial equivalence of VMAT and IMPT. Organs' at-risk planning aims were achieved for all structures for both techniques but IMPT plans presented the best results. Robust optimization impacted on the near-to-maximum dose values for contralateral lung and breast, on the mean dose for the heart and ipsilateral lung. The numerical values of EAR per 10′000 patients-year resulted about one order of magnitude higher for VMAT then for IMPT for contralateral structures (∼11-14 vs ∼0.9-1.4 for VMAT and IMPT respectively) and about a factor two for the ipsilateral lung (∼35 vs 19). The robust optimization methods induced a deterioration in the EAR estimates.

Conclusion: This study suggests that IMPT is a potentially promising approach for the radiation treatment of advanced breast cancer when nodal volumes should be irradiated. Clinical trials should be performed to demonstrate the anticipated dosimetric benefit.


Dosimetric comparison of proton versus photon therapy for bilateral breast/chest wall and comprehensive nodal irradiation for synchronous bilateral breast cancer

A. Garda1, S. Fattahi2, A. Michel1, R. Mutter1, E. Yan1, S. Park1, K. Corbin1

1Mayo Clinic, Department of Radiation Oncology, Rochester, MN, USA, 2Mayo Clinic, Mayo Clinic Alix School of Medicine, Rochester, MN, USA

Purpose: Adjuvant radiotherapy for synchronous bilateral breast cancer poses distinct treatment planning challenges. This study is a dosimetric comparison of proton beam therapy (PBT) versus photon therapy for bilateral breast/chest wall and comprehensive nodal irradiation (RNI) for synchronous bilateral breast cancer.

Methods: Patients with synchronous bilateral breast cancer treated with bilateral radiotherapy to the breast/chest wall and RNI at our institution between 2015 and 2018 were identified. Comparison plans were generated by an experienced dosimetrist and reviewed by a radiation oncologist.

Results: Nine patients were included in this analysis. Volumes included bilateral postmastectomy radiotherapy (n=7), bilateral whole breast radiotherapy with RNI (n=1), and postmastectomy and whole breast radiotherapy with RNI (n=1). CTV included breast/chest wall and regional lymph nodes, including axilla, supraclavicular fossa, and internal mammary chain. PTV was 5 mm expansion on CTV. Prescription to the CTV (PBT) or PTV (photon) was 50 Gy (or relative biological effectiveness 1.1) in 25 fractions. Five patients received boost to chest wall (n=2), lumpectomy cavity (n=1), and nodal regions (n=3). Boost was delivered as simultaneous integrated boost to 54.05-58.75 Gy in 25 fractions (n=5) or sequential boost of 12.5 Gy in 5 fractions (n=1). Table 1 lists dose received by 90% and 95% of volume (D90% and D95%, respectively). Table 2 lists dose to organs at risk.

Conclusion: Bilateral breast/chest wall and comprehensive nodal PBT for synchronous bilateral breast cancer is associated with improved target coverage and normal tissue sparing compared to photon therapy. PBT is an attractive treatment option for these complex patients.


Re-irradiation of recurrent cancer in the breast and chest wall using intensity modulated proton therapy

H. Giap1

1University of Miami Sylvester Comprehensive Cancer Center, Radiation Oncology, Miami, FL, USA

Background: Treatment management is challenging in patients with local recurrence of breast cancer who had previous radiation therapy. This series described technique and outcome for 10 such patients treated at Scripps Proton Therapy Center.

Methods: Of 10 patients in this category, two patients needed chest wall radiation after resection of recurrent cancer due to positive margins; seven patients had gross nodal and chest wall recurrence; one patient had post-lumpectomy radiation in previously irradiated area from another malignancy. All patients except one (23.4 Gy) had previous full dose radiation to 50 Gy or higher. Patients, immobilized with either a breast board or Vac-Q-Fix cushion, were set up in the supine position with arms over their head. One to two beams using IMPT with MFO technique was used. Dose was prescribed at 1.8-2 Gy to 50 to 60 Gy daily treatment. Weekly adaptive simulation was done with CT. Photographs were obtained during and after treatment. All cases were reviewed and approved by our weekly physicist and physician treatment planning conference.

Results: No patients had more than grade 2 skin acute toxicity. There was no Grade 3 or greater late toxicity. One patient developed grade 2 lymphedema. Only one patient had local failure, and two died from distant metastases.

Conclusion: IMPT is feasible and a safe modality for re-treatment of recurrent cancer in the breast and chest wall. Further validation with more patients and longer follow-up is needed.


Accelerated partial breast irradiation (APBI) with intensity modulated proton therapy (IMPT) for patients with breast augmentation

H. Giap1

1University of Miami Sylvester Comprehensive Cancer Center, Radiation Oncology, Miami, FL, USA

Background: Patients with early stage breast cancer and breast augmentation often require mastectomy or have significant cosmetic issues from whole breast irradiation. We describe technique and outcome in six patients treated at Scripps Proton Therapy Center.

Methods: All patients have either T1 No ductal (5) or uni-focal DCIS (1). All patients met ASTRO criteria for APBI. All patients underwent CT based simulation and treatment planning and were set up supine on a breast board or in the prone position. Daily setup and localization were accomplished with 3-4 skin surface fiducial markers tracked with orthogonal x-ray pairs. 40 Gy and 34 Gy in 10 treatments were prescribed lumpectomy cavity and lumpectomy cavity plus 1-1.5 cm excluding chest wall and skin. Treatment was delivered using IMPT with a single enface field with simultaneous integrated boost.

Results: Mean total patient time in treatment room was 14 minutes. Mean heart dose was < 0.2 Gy and mean lung dose < 1 Gy. Most patients experienced grade 1 dermatitis, and 2 with grade 2. With a mean follow up time of 25 months, 3 patients had minor dry skin in the treatment area and no other late toxicities or problem with the breast implant. All patients self-reported ‘good to excellent' cosmetic outcomes. No patients had evidence of local failure.

Conclusions: Single field IMPT is a safe, feasible and effective approach for APBI in early stage breast cancer patients with breast augmentation.


Dosimetric comparison of intensity modulated proton therapy (IMPT) versus volumetric modulated arc therapy (VMAT) on early stage left breast cancer

W.W. LAM1, H. Geng1, K.K. Tang1, T.Y. Lee1, C.W. Kong1, B. Yang1, T.L. Chiu1, K.Y. Cheung1, S.K. Yu1

1Hong Kong Sanatorium & Hospital, Medical Physics & Research Department, Hong Kong, China

Purpose/Objectives: To evaluate the dosimetric impacts of IMPT as compared with VMAT using photon on early stage left-sided breast cancer.

Materials and Methods: Six early stage left-sided breast cancer patients treated by post-lumpectomy irradiation with 4 partial arcs VMAT were retrospectively re-optimized using IMPT. One single left anterior oblique IMPT field was used for optimization using Varian Eclipse proton TPS. In both IMPT and VMAT planning, simultaneous integrated boost technique was used to give 58 Gy(RBE) to GTV (tumor bed) and 50 Gy(RBE) to PTV (whole left breast) in 25 fractions, assuming RBE of 1.1 and 1 for proton and photon, respectively. GTV and PTV coverage, dose conformity and homogeneity were reported by dose received by 95% and 98% target volumes (D95, D98), conformity number (CN) and homogeneity index (HI). Mean dose (Dmean), near-maximum dose (D2), percentage organ volume receiving more than 5, 10, 20 Gy(RBE) (V10,V20,V30) of heart, contralateral breast, left and right lungs were compared. Dmean, D2, V30, V40 and V50 of skin (a layer structure of 2mm inward from the body contour on irradiated side) were also evaluated. Statistical analysis was performed using Wilcoxon-signed rank test. A two-tailed p<0.05 was considered statistically significant.

Results: All results were tabulated in Table 1.

Conclusion: Higher skin dose was observed in IMPT, but it could significantly lower doses to heart, contralateral breast, left and right lungs while provided better target coverage and comparable conformity and homogeneity as compared with 4 partial arcs VMAT in post-lumpectomy left-sided breast cancer.


A treatment planning study for bilateral breast irradiation comparing intensity modulated proton therapy to 3D and intensity modulated photon therapy

M. Ma1, X. Gao1,2, Z. Zhao2, B. Zhao1

1Peking University First Hospital, Radiation Oncology, Beijing, China, 2Zhouzhou Proton Center, Proton therapy, Zhuozhou, China

Objective: Delivery of irradiation in women with bilateral breast conserving surgery represents a technical challenge. The purpose of this study was to compare IMPT to single isocenter bilateral tangential 3D conformal fields combined with IMRT (3D/IMRT) and VMAT in bilateral breast radiotherapy.

Methods: IMPT plans, 3D/IMRT and VMAT photon plans were created for 5 patients with synchronous bilateral breast cancer. The conventional dose (50Gy/25f to whole breast and 60Gy/25f to tumor bed) was delivered. The 3D/IMRT plans used 8-11 fields, including 4 tangential ones; Only one field was delivered in VMAT plans; for IMPT, fields were used in 5°, 20° and 340°, 355° to avoid motion uncertainties.

Results: IMPT and VMAT plans conferred higher target volume coverage as compared with 3D/IMRT (p=0.0079 for tumor bed, 0.037 for whole breast). V107 were 13.7±4.8%, 0.4±0.4% and 0.56±0.40% for tumor bed and 25±2.4%, 22.69±2.2% and 13.1±4.3% for the breast subtract tumor bed using 3D/IMRT, VMAT and IMPT. The results of Dmean and V20Gy of lungs using 3D/IMRT(9.3±0.4Gy and 17.2±0.9%) and VMAT(10.26±0.8Gy and 15.9±1.9%) were comparable, while it was lower in IMPT plan(2.6±0.7Gy and 4.6±1.1%). The meanV5Gy in VMAT plans(44.9±3.4%) were the highest while it was still the lowest in IMPT plans(12.5±2.1%). Also, VMAT resulted in highest Dmean to heart(7.6±0.6Gy) than 3D/IMRT(5±1.1Gy) and IMPT(0.52±0.3Gy). Doses for left anterior descending coronary artery were significantly decreased as well using IMPT(Fig.1).

Conclusion: IMPT provides improved homogeneity with excellent sparing of surrounding normal structures. Lower doses for lungs and heart were higher using VMAT compared to either IMPT or 3D/IMRT.


Dosimetric evaluation of proton beam radiotherapy for clinically gross internal mammary lymph node metastasis in breast cancer

T. Mullikin1, D. Routman1, A. Garda1, R. Mutter1, K. Corbin1

1Mayo Clinic, Department of Radiation Oncology, Rochester, MN, USA

Purpose: Radiotherapy targeting of breast cancer internal mammary lymphadenopathy is challenging. Our purpose was to report target coverage and organs at risk (OAR) dosimetry of intensity modulated proton therapy (IMPT) for the treatment of breast cancer with clinically gross internal mammary lymph node (IMN) metastases.

Methods: We identified patients with breast cancer and clinically-involved, unresected IMN metastases treated with lumpectomy or mastectomy followed by IMPT with IMN boost at our institution between 2015 and 2018. Patients with other sites of unresected regional lymph node disease were excluded.

Results: Ten eligible women were identified. Mean age was 47.9 (R: 38-65). Nine of 10 patients were left-sided. Nine of 10 patients were clinical T2-T3. Nine patients were clinical N3b and 1 patient was clinical N2b. Surgery was mastectomy in 9 and lumpectomy in 1. The clinical target volume (CTV) included the chest wall or breast and axillary, supraclavicular, and IMNs, and was treated to a median dose of 50 Gy (RBE 1.1) in 25 fractions with one patient receiving a sequential chest wall boost to 60 Gy. All patients received a boost to un-resected IMNs. Median IMN boost dose was 5625 cGy (R: 5375- 6000) delivered as a simultaneous integrated boost in 9 patients. Table 1 lists the CTV coverage for the IMN boost and OAR.

Conclusion: For the treatment of clinically gross IMN metastases in breast cancer, radiotherapy boost with IMPT provides exceptional target coverage and normal tissue sparing.


Monoisocentric intensity modulated proton therapy technique for bilateral chest wall and regional nodal radiotherapy

J. Yu1, K. Greco1, M. Fagundes1

1Miami Cancer Institute, Radiation Oncology, Miami, FL, USA

Purpose: To report a novel monoisocentric technique to deliver bilateral chest wall and comprehensive nodal radiotherapy using IMPT.

Methods and Materials: Patient, RC, is an 83 y.o. female with bilateral breast cancer ER/PR+, Her-2 -, post bilateral mastectomy, axillary dissection, with right breast pmT2N1 2.5 cm invasive ductal carcinoma, 2/19 +LNs; left breast pT2N2a IDC 3.4 cm 6/12 + LNs. Adjuvant IMPT was delivered to the bilateral chest walls, axillary, supraclavicular and internal mammary lymph nodes on the right side. The prescribed dose was 50.4 Gy (RBE) in 28 fractions. An IMPT plan was generated using a single isocenter without any couch rotation or shift to maximize delivery efficiency. The plan was robustly optimized with multiple field optimization using three fields-AP, LAO and RAO. In between the fields, gradient junctions of approximately 8 cm were created to improve setup robustness (Fig1). Non-ionizing surface imaging was used for initial patient set up and intra-fraction motion monitoring.

Results: The heart mean dose was 0.06 Gy with total lung V20Gy and V5Gy of 8% and 21%. Total CTV D99% was 50.4 Gy in nominal plan, and 47 Gy in the worst-case scenario (5 mm setup errors and 3.5% range uncertainty) in robustness evaluation. For daily patient setup, the Intra-fraction motion monitored by the surface imaging was within 3.5 mm variations (Fig2).

Conclusions: This monoisocentric, IMPT approach is a novel and highly efficient technique to deliver bilateral chest wall and comprehensive nodal radiotherapy with favorable target coverage, cardiac and lung sparing.

Clinics: Lung, PTC58-0204

Commercial vs. in-house developed IMPT treatment planning system for lung cancer: a treatment planning comparison

C. Liu1, J. Shan1, T. Daniels1, W. Rule1, T. DeWees2, Y. Hu1, X. Ding1, M. Bues1, T. Sio1, W. Liu1

1Mayo Clinic Arizona, Radiation oncology, Phoenix, AZ, USA, 2Mayo Clinic Arizona, Division of Biostatistics, Phoenix, AZ, USA

Purpose: To compare intensity-modulated proton therapy (IMPT) plans generated by our in-house developed treatment planning system (TPS) (SoloTM) and the commercial TPS (cTPS) for lung cancer.

Methods and Materials: We selected 10 lung cancer patients. Two IMPT plans were created using SoloTM and cTPS. The plans were designed to deliver the prescription doses to internal target volumes (ITV) on averaged 4D-CTs. SoloTM plans were imported back to cTPS and recalculated to get the final dose distributions in cTPS for fair comparison. Both plans of each patient were further verified in CT0 and CT50 phases and all plans met the clinical requirements. Plan robustness on all phases was quantified using dose-volume-histograms (DVH) band method. Interplay effects were evaluated by the in-house developed software for every plan, which randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test.

Results: Compared to plans generated by cTPS, in nominal scenario SoloTM plans delivered significantly lower esophagus V60Gy[RBE] and Dmean, and cord Dmax with better robustness in target coverage, homogeneity, hot spots, and lung Dmean. In CT0 and CT50 phases, SoloTM plans had better ITV dose coverage and cord Dmax with comparable robustness. In term of interplay effects, SoloTM plans had statistically better target dose coverage, and lower esophagus Dmean and cord Dmax.

Conclusions: SoloTM generated IMPT plans of higher quality, and comparable or better plan robustness in all phases and interplay effects. Our study supports the usage of SoloTM to design IMPT plans for lung cancer patients.


Mitigation of interplay effects with layer repainting techniques in intensity modulated proton therapy for early stage non-small cell lung cancer

H. Shang1,2, L. chenbin3, P. yuehu1, W. yuenan4

1Shanghai Institute of Applied Physics, Beam Measurement and Control Department, Shanghai, China, 2Raysearch Labs China, Services, Shanghai, China, 3Mayo Clinic Arizona, Department of Radiation oncology, Phoenix, AZ, USA, 4Chinese Academy of Medical Science CAMS Shenzhen Cancer Hospital, Department of Radiation Oncology, Shenzhen, China

Ten patients with early staged NSCLC were enrolled and 4D robust IMPT treatment plans were performed. In the development of treatment plans, the uncertainties of Monte Carlo dose engine were 0.5% and dose grid resolution was 3mm; setup and range uncertainties were 5mm and 3%, respectively. We applied layer repainting techniques with different numbers of repainting (3, 4, 5, 6, 7 times) and evaluated differences in the mitigation of interplay effects. We evaluated the treatment plans withT50 as the reference CT, and all other CTs were aligned to T50 using hybrid deformable method. 4D static dose was the accumulated dose on all the phases. To assess the 4D dynamic dose, we simulated the respiratory cycles with T50 as the starting phase, recalculated the doses on 10 phases continuously, and accumulated the doses to T50. In order to evaluate interplay effects, we calculated the difference of DVH indices between 4D static dose and 4D dynamic dose for CTV and lungs. Due to interplay effects, the mean values of target coverage, conformity and homogeneity index reduced by 14.0%, 12.6% and 23.8%, respectively. The mean values of lung V5Gy[BRE] and V20Gy[RBE] improved by 3.1%, 2.1% and 2.9%.With all different of layers repainting, mean values of target coverage, conformity and homogeneity index could be increased but was still in lower 5% compare with 3D dose. In addition, average values of lung V30Gy[RBE] improved by 2.4%, 2.7%, 4.9%, 4.4%, and 4.4%, respectively. This study reveals that IMPT is not suitable for early staged NSCLC only use repainting.


Protons increases BED compared with photons in partial stereotactic ablative boost radiotherapy for large NSCLC

Y. Bai1, X.S. Gao1, Z.L. Zhao2, M.W. Ma1, X.Y. Ren1

1Peking University First Hospital, Department of Radiotherapy, Beijing, China, 2Yi Zhou Proton Therapy Center, Department of Radiotherapy, Hebei, China

Purpose: Photons Partial Stereotactic Ablative Boost Radiotherapy (P-SABR) is able to achieve high local control rate while keeping the side effect well tolerated in large NSCLC (diameter >5cm) according to our previous research. We also find that larger tumor volume receiving high BED could increase local control in radiotherapy. This study aims to further explore whether protons can elevate the tumor volume receiving high BED compared with photons.

Methods: We planned 30 patients who previously received P-SABR with photons for large NSCLC. The patients underwent repeat planning for intensity-modulated proton beams (2-3 beams) (“IMPT” for short), proton arc beams (10-14 beams to simulate ARC) (“PAT” for short) and photon IMRT, VMAT plans. P-SABR plans were described before. GTV boost is the max volume receiving SABR and the protons plans were created to achieve comparable RBE of GTV margin to photons plans. Dosimetric variables were acquired in both proton and compared photon plans.

Result: Both IMPT and PAT could achieve higher B90 (the ration of volume of BED>90Gy to the in-field tumor), B100 and B110 than photons plans(P<0.05). D75 (volume of the structure receiving RBE >75 GyE), D80, D85 and D90 were also larger for proton than for photon P-SABR(P<0.05). In addition, despite the RBE for esophagus were similar (P>0.1), protons plan could significantly reduce the RBE for other OARs (P<0.05).

Conclusion: Larger tumor volume receiving high BED was achieved by protons compared with photons. Protons P-SABR might increase the local control rate while reducing the side effect for large NSCLC.


Proton radiotherapy to improve non-small cell lung cancer outcomes: Two clinical study proposals

A. Salem1, D. Woolf2, M. Aznar1, A. Azadeh3, C. Eccles1, F. Charlwood4, C. Faivre-Finn1

1University of Manchester/ Christie NHS Foundation Trust, Division of Cancer Sciences/ Radiotherapy Related Research & Department of Clinical Oncology, Manchester, United Kingdom, 2Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom, 3University of Manchester/ Christie NHS Foundation Trust, Division of Cancer Sciences/ Radiotherapy Related Research, Manchester, United Kingdom, 4Christie NHS Foundation Trust, Christie Medical Physics and Engineering, Manchester, United Kingdom

Background: There is limited supporting evidence for proton radiotherapy in non-small cell lung cancer (NSCLC); thoracic proton radiotherapy research is required.

Objective: We propose two clinical studies which will likely be the UK first clinical proton radiotherapy studies and the first translational thoracic proton radiobiology program.

Clinical study 1

Concurrent chemoradiotherapy followed by durvalumab is the new standard-of-care in stage III NSCLC. Preclinical evidence supports that proton radiotherapy has higher tumor immunogenic and lower normal tissue immunosuppressive effects, compared to photon radiotherapy.

Design: Randomized proof-of-concept biomarker study (n=66).

Main hypothesis: Baseline and longitudinal immune-related biomarkers (tissue & blood) provide data on differences between proton and photon radiotherapy/ immune interactions.

Secondary hypotheses:

  1. Proton radiotherapy increases adjuvant durvalumab initiation secondary to reduced toxicity and non-inferior tumor control, compared to photon radiotherapy

  2. Protons reduce cardiac morbidity from thoracic radiotherapy, as quantified using longitudinal cardiac biomarkers (cardiac CT, echocardiography & blood)

Clinical study 2

Locoregional recurrence after (chemo)radiotherapy is common in NSCLC and could be salvaged with a repeat radiotherapy course. Photon re-irradiation is associated with significant toxicity. Targeting tumor hypoxia, which is associated with radiotherapy resistance and poor survival, could improve NSCLC outcomes.

Design: Single arm 2-stage proof-of-concept study (n=40).

Main hypothesis: Proton re-irradiation is safe in recurrent NSCLC.

Secondary hypotheses:

  1. Nimorazole (a hypoxic radiosensitizer) improves patient survival when added to proton re-irradiation, without increasing radiotherapy-related adverse-events

  2. Hypoxia biomarkers (imaging & tissue) predict benefit from nimorazole

  3. Patient reported outcome measures reduce thoracic re-irradiation morbidity and mortality


Photon vs proton therapy for reduction of cardiac toxicity in locally advanced lung cancer using the model-based approach

S. Teoh1, F. Fiorini1, B. George1, K. Vallis1, F. Van den Heuvel1

1University of Oxford, CRUK and MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom

Purpose/Objective: To identify a sub-group of patients with locally advanced lung cancer who would benefit from proton beam therapy (PBT) compared to photon therapy for reduction of cardiac toxicity using the model-based approach.

Material and Methods: Volumetric modulated arc photon therapy (VMAT) and robust-optimised intensity modulated proton therapy (IMPT) plans were generated to a physical dose of 70Gy in 35 fractions. Cases were selected to represent varying anatomical locations of primary tumor and nodal involvement (15/20 had nodal involvement). Contouring and treatment planning followed RTOG-1308. Dose to the heart and sub-structures were compared. Risk estimates of grade 3+ cardiac toxicity were calculated based on models which incorporated dose metrics and patients' risk-factors.

Results: There was no statistically significant difference in target coverage between VMAT and IMPT. Overall IMPT delivered lower doses to the heart (mean, V5 and V30). In VMAT plans, there were statistically significant positive correlations between heart dose and thoracic vertebral level that coincided with the lower limit of the tumor. Between VMAT and IMPT, there was no statistically significant difference in dose to the heart or sub-structures when disease (primary and nodes) extended above T7 vertebrae. When disease extended to and below T7 vertebrae IMPT delivered lower doses to the heart and sub-structures (mean, V5 and V30, P<0.001). Risk estimates for cardiac toxicity for these patients are presented in Table 1.

Conclusion: Patients with tumor extension to and below T7 vertebrae are likely to benefit most from proton over photon therapy. The absolute benefit is higher in patients with underlying cardiac disease.

Clinics: GI, PTC58-0726

Re-irradiation of rectal and anal cancer with intensity modulated proton therapy (IMPT) and endo-rectal balloon

H. Giap1

1University of Miami Sylvester Comprehensive Cancer Center, Radiation Oncology, Miami, FL, USA

Background: Treatment management is challenging in patients with local recurrence of anal-rectal cancer (LR-ARC) who had received previous radiation therapy. We described our clinical experience using IMPT and endo-rectal balloon for the re-irradiation of these patients which had partial circumferential tumor recurrence.

Methods: Seven patients of LR-ARC with less than 2/3 of the circumference involvement, treated at Scripps Proton Therapy Center were selected. EUS was done for depth and circumference involvement. Trans-rectal debulking of tumor was encouraged. Patients were set up in the supine position and the Radiadyn ImmobiLoc endo-rectal balloon (ERB) is used and inflated with water to as big the volume as patient could tolerated. All patients underwent CT and MRI based simulation. GTV is defined as tumor seen on CT/MRI/PET scan, and CTV is defined as GTV with a 5 mm margin. No elective nodal volumes were treated. Daily fraction of 1.8-2 Gy for 50.4 to 54 Gy to the CTV and 56-60 Gy to GTV given simultaneously. Treatment was delivered with 1-2 beams. All patients had daily orthogonal kV x-rays and CBCT, weekly adaptive plan, and concurrent chemotherapy.

Results: All patients finished treatments, and none had > grade 2 rectal toxicity. With a mean follow up time of 29 months, 5 of 7 patients still alive. 3 patients with CR, 2 with PR, and 3 with PD. One immunocompromised (HIV) patient had grade 3 ulceration requiring hyberbaric oxygen and wound care.

Conclusion: Re-irradiation using IMPT and ERB in selected patients is technically feasible with acceptable toxicity.


Short-course preoperative pencil beam proton therapy for rectal cancer: A pilot study

E.Y. Huang1, P.J. Juang1

1Kaohsiung Chang Gung Memorial Hospital, Radiation Oncology, Kaohsiung, Taiwan

Purpose: To evaluate the feasibility, dosimetry, and complications of short-course preoperative proton beam therapy for rectal cancer.

Materials and Methods: From October 2018 to January 2019, 2 male patients with Stage III rectal cancer planned by short-course preoperative radiotherapy were included in this study. The dose of radiotherapy was 25 CGE/5 fractions. Pencil beam proton therapy system (Sumitomo Heavy Industries) using single-field uniform dose (SFUD) was delivered through 2 posterior oblique fields (135 and 215 degree). Doses of pelvic bone marrow, small bowel, and penile bulb were calculated using RayStation 6.0 planning system. Image-guided cone beam CT was used before each treatment. Acute toxicities of radiotherapy were evaluated by common toxicity criteria (CTC) version 4.

Results: Dosimetries of pelvis bone marrow (V2.5=45.9±12.0% vs. 85.6±9.1%; V5=40.4±10.5% vs. 79.6±9.8%; V7.5=35.8±8.6% vs. 75.7±10.3%; V10=29.7±4.9% vs. 62.8±7.9%), small bowel (V10=58.6±39.3 mL vs. 142.9±94.0 mL; V15=50.3±34.3 mL vs. 73.9±37.4 mL; V20=41.5±28.4 mL vs. 47.3±30.6mL), and penile bulb (mean dose=6.4±1.7 CGE vs. 12.1±1.3 CGE) were better than VMAT planning. One patient completed proton therapy then received surgery within 1 week. No Grade 1 or greater leukopenia, dermatitis and diarrhea were noted before or after operation.

Conclusion: Short-course preoperative pencil beam proton therapy for rectal cancer is feasible because of better dosimetries of pelvic bone marrow, small bowel, and penile bulb. Further prospective study is considered for short-term and long-term outcomes.


ProtOeus: Consideration of interplay effects for the proposed oesophageal trial

S. Pan1, F. Charlwood2, M. Hawkins3, M. Clarke2, M. Lowe2, G. Radhakrishna1

1The Christie NHS Foundation Trust, Proton Beam Therapy, Manchester, United Kingdom, 2The Christie NHS Foundation Trust, Physics- Proton Beam Therapy, Manchester, United Kingdom, 3CRUK/MRC Oxford Institute of Radiation Oncology, Radiation Oncology, Oxford, United Kingdom

Background: Neoadjuvant chemoradiation prior to definitive surgery in locally advanced oesophageal cancer has shown improved outcomes in the CROSS trial. However, the anatomical position, size and proximity of the tumor to surrounding structures, poses a conundrum as there is a high integral dose to neighbouring organs, which may translate to an increased perioperative risk and worse long-term outcomes. The aim of ProtOeus is to test the validity of this hypothesis.

Methods: In preparation for the UK-based trial - ProtOeus, a comparison of treatment plans with photons and protons was made in a patient with 'flip-flop' oesophageal tumor. The interval target volume (ITV) was delineated over ten 4DCT phases. A three-beam posterior oblique single field optimisation (SFO) plan was created on the maximal exhalation phase (MEP). Velocity 4.0 was used to study the effect of respiratory motion and change in water equivalent thickness (WET). The nominal proton plan with repainting was recalculated and the dose was deformed back to MEP. The effect of interplay was studied by taking into account spot delivery time and breathing rate.

Results: Target doses between photons and protons were comparable, but reduced dose to the heart, liver and lung with protons. Doses to the tumor and organs at risk (OARs) are relatively unaffected in ten different simulated starting points of respiratory cycle.

Conclusion: The initial results are promising that protons may have a potential role in reducing dose to surrounding structures. We will be exploring this approach further with Monte Carlo planning dose calculations and validate it with other cases.


Functional liver imaging for hepatotoxicity risk prediction in primary liver cancer patients with cirrhosis treated with proton therapy

S. Schaub1, S. Bowen2, M. Nyflot2, T. Chapman3, S. Apisarnthanarax4

1University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA, USA, 2University of Washington School of Medicine, Departments of Radiation Oncology and Radiology, Seattle, WA, USA, 3Beth Israel Deaconess Medical Center- Harvard Medical School, Department of Radiation Oncology, Boston, MA, USA, 4University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA, USA

Background: There is an unmet need for objective and radiotherapy modality specific metrics for mitigating radiation-induced liver disease (RILD) in primary liver cancer (PLC) patients with cirrhosis. We hypothesize that [99mTc]-sulfur colloid (SC) SPECT/CT can provide global and spatial metrics for improved RILD-risk stratification in patients treated with proton therapy (PT).

Methods: We retrospectively reviewed 47 patients treated with PT with Child-Pugh (CP)-A (68%) or CP-B/C (32%) cirrhosis that underwent pretreatment SC SPECT/CT scans. SC SPECT imaging was mined for intensity threshold-based functional liver volumes (FLV), mean liver-spleen uptake ratio (L/Smean), and total liver function (TLF = FLV*L/Smean). Cox regression was performed for correlation to RILD-specific survival (RILD-SS) and overall survival (OS) and logistic regression for correlation to CP-score 2+ and/or grade 3+ liver enzymes (CP+2/LFTs).

Results: Baseline CP-score (p=0.003) and functional liver parameters of FLV (p=0.023), L/Smean (p=0.003), and TLF (p=0.003) were significant univariate predictors of RILD-SS, but not CT-derived anatomic dosimetric metrics. Risk stratification using TLF > 0.65, representative of high global liver function, into low and high-risk subgroups predicted for a 100% vs 17% 1-year RILD-SS (p<10E-6). Functional liver imaging metrics remained independently associated with RILD-SS when adjusting for CP-score. Global metrics of TLF (p=0.013) and L/Smean (p=0.040) were superior predictors of RILD-SS relative to CP-score (p>0.6). Whereas baseline CP-score was the only significant factor for CP+2/LFTs prediction (p=0.016), functional liver metrics retained significance when evaluating for OS.

Conclusions: Baseline functional imaging liver metrics improved hepatotoxicity risk prediction in PLC patients treated with PT.


Is a squamous cell carcinoma (SCC) of the anus indeed a reasonable target of proton beam radiotherapy (PBT)?

P. Vitek1, J. Kubes1, V. Vondracek1, S. Vinakurau1, L. Zamecnik1

1Proton Therapy Center Czech, Proton radiotherapy, Praha 8, Czechia

Chemoradiotherapy is a standard treatment for anal SCC. Myelotoxicity often results in treatment interruptions. For IMRT a grade 3-4 myelotoxicity occurs in up to 61%. Pencil beam scanning (PBS) PBT significantly decreases the doses in bone marrow (BM), bladder, small intestine, hip joint. The efficacy, toxicity and dosimetric data were analysed to assess the role of PBT.

PBS PBT was administered in 21 patients with anal SCC, stage T2N0M0–T4N3M0. Simultaneous integrated boost has been used in all patients – PTV-1, tumor with margin and involved lymph nodes 57,5 GyE, PTV-2 regional lymph nodes 45 GyE, both in 25 fractions, 5 fractions/week. Concomitant chemotherapy: CDDP+capecitabine.

The prescribed dose was administered in all patients. Median follow-up is 25 months. Chemotherapy was reduced in 3 patients. The median of V10GyE in BM was 64%. Medians of Dmean in abdominal cavity, bladder and hip joints were 13,8 GyE, 12,74 GyE, and 24,8 GyE respectively. The acute toxicity was predominantly mucocutaneous, gr.3 24%, diarrhoea, gr.3 9,5%, 1 episode of neutropenia gr.4 (not febrile) and 1 gr.3. A treatment interruption (2 d) required in 1 pt. 6 pts. (28,5%) developed late radiation proctitis gr. 2 (5 pts.) gr. 3 (1 pt.), median onset 6 months. Complete regression was achieved in 19 pts, 1 salvage surgery, 1 salvage chemotherapy was required.

The acute toxicity is moderate, predominantly cutaneous. Myelotoxicity is mild, maintaining continuous treatment course. Late radiation proctitis poses the most serious complication. A good efficacy and favourable toxicity profile related to excellent dosimetry supports PBS PBT for anal SCC.


PIOPPO TRIAL: Phase 2 study for preoperative treatment of operable or borderline operable adenocarcinoma with chemotherapy and carbon ion hadrontherapy

V. Vitolo1, A. Barcellini1, S. Brugnatelli2, L. Cobianchi3, A. Vanoli4, P. Fossati1, A. Facoetti5, P. Dionigi3, F. Valvo1, R. Orecchia6

1National Center of Oncological Hadrontherapy Fondazione CNAO, Radiation Oncology, Pavia, Italy, 2Fondazione IRCCS Policlinico San Matteo, Medical Oncology, Pavia, Italy, 3Fondazione IRCCS Policlinico San Matteo, General Surgery, Pavia, Italy, 4Fondazione IRCCS Policlinico San Matteo, Pathology, Pavia, Italy, 5National Center of Oncological Hadrontherapy Fondazione CNAO, Radio Biology, Pavia, Italy, 6National Center of Oncological Hadrontherapy Fondazione CNAO- European Institute Of Oncology, Radiation Oncology, Pavia- Milano, Italy

Introduction The purpose of PIOPPO trial is to assess the role of neoadjuvant chemotherapy followed by carbon ion hadrontherapy (CIRT) for patients (pts) with resectable (rPC) or borderline resectable pancreatic cancer (brPC). Primary endpoint is local PFS and secondary endpoints are OS, R0-resectability rate and treatment toxicity (including intra and perioperative toxicity).

Methods: PIOPPO is a prospective, phase II, multicenter and single-arm study. Thirty patients will be enrolled in the study. Sample size has been defined with an expected probability of success proportion of success at 24 months of 60% vs 35% (H0: p <= 0.35-H1: p> 0.35). Enrolled patients, with a rPC/brPC, underwent to 3 cycles of FOLFIRINOX followed by CIRT (total dose:38.4 Gy [RBE], 8 fractions, 4 fractions per week). 4D and breath gated planning is performed and rescanning is carried out. GTV is established using CT, MRI and PET. CTV is GTV with 5 mm margin, locoregional elective lymph node and neuroplexus region. From 4 to 6 weeks after completion of CIRT pts will undergo conventional pancreatic surgery. Subjects who meet the enrolment criteria but decline to participate in the study will serve as controls. Adjuvant chemotherapy is given according to clinical practice.

Results: Since January 2018 five patients have been so far enrolled and four have completed the surgical phase. No significant acute toxicities, including surgery-related have been observed.

Conclusions: Our first experience is promising and CIRT does not affect negatively the surgical approach. The combined treatment of PIOPPO trial for rPC/brPC is safe and feasible.


Clinical impact of re-irradiation with carbon ion radiotherapy for locally recurrent rectal cancer

V. Vitolo1, A. Barcellini1, A. Iannalfi1, B. Vischioni1, A. Facoetti2, S. Ronchi1, E. D'Ippolito1, R. Petrucci1, F. Valvo1, R. Orecchia3,4

1National Center of Oncological Hadrontherapy Fondazione CNAO, Radiation Oncology, Pavia, Italy, 2National Center of Oncological Hadrontherapy Fondazione CNAO, Radiation Biology, Pavia, Italy, 3National Center of Oncological Hadrontherapy Fondazione CNAO-, Radiation Oncology, Pavia, Italy, 4European Institute of Oncology, Radiation Oncology, Milan, Italy

Purpose: The re-irradiation (reRT) of locally recurrent rectal cancer (LRRC) presents challenges due to the proximity of critical organs such as bowel. Carbon ion radiotherapy (CIRT) could be a treatment option for conventionally difficult-to-cure patients (pts)

Aim: to evaluate safety and efficacy of reRT with CIRT in previously irradiated LRRC pts

Patients and Methods: Between 2014 and 2017, 10 pts were treated with CIRT as reRT for LRRC at CNAO. All pts had a history of surgery for RC and pelvic radiotherapy (in one case radiotherapy was delivered for prostatic cancer). At time of the first recurrence, 1 pt underwent to reRT with stereotactic radiotherapy. Three pts received surgical spacer implantation to keep bowel apart for the tumor.

Results: Patient, tumor and treatment details are summarized in Table I. All patients completed the treatment. Acute toxicity was mild and mainly neuropathy (G2:10%; G1:20%). Median follow-up was 13 months. We observed 20% of G2 late peripheral neuropathy. No G≥3 acute/late reaction nor pelvic infections were reported. Four pts experienced local progression after CIRT (median disease-free survival: 11.4 months). Three pts experienced systemic progression. The estimated 1-year-local control rate was 80%.

Conclusion: reRT with CIRT for LRRC appears to be safe and effective with an acceptable rate of morbidity of normal tissue. More data and longer follow-up are required to investigate the long-term disease control and to determine late effects.


The effectiveness of proton beam therapy for liver metastatic recurrence in gastric cancer patients

H. Yamaguchi1, M. Honda2, K. Hamada3, Y. Todate4, I. Seto1, M. Suzuki1, H. Wada1, M. Murakami1

1Southern Tohoku Proton Beam Therapy Center, Department of radiology, Koriyama, Japan, 2Fukushima Medical University, Department of Minimally Invasive Surgical and Medical Oncology, Fukushima, Japan, 3Southern Tohoku General Hospital, Department of gastroenterology, Koriyama, Japan, 4Southern Tohoku General Hospital, Department of Surgery, Koriyama, Japan

Background: Liver metastasis from gastric cancer (LMGC) is a noncurable, fatal disease with a 5-year survival rate of <10%. Proton beam therapy (PBT) is expected to be an effective therapeutic method for LMGC. The purpose of this cross-sectional study is to evaluate the safety and efficacy of PBT.

Methods: The consecutive patients who underwent PBT from 2010 to 2015 were isolated from institutional database. Patients with extrahepatic metastatic lesions were excluded. The effectiveness was assessed local control (LC), overall survival (OS) and progression-free survival (PFS). Adverse events were described according to the Common Terminology Criteria for Adverse Effects version 4.03.

Results: Seven patients were enrolled. The median diameter of target lesions was 31 mm (13−68). The most frequent dosage was 72.6 Gy (RBE) in 22 fractions. All patients completed PBT without interruption. The median follow-up period was 41.7 months (20.7−66.3). The 3-year LC rates was 85.7%. The 3-year OS rates was 68.6%. The 3-year PFS rates was 43%. No grade 3 or more severe adverse events were observed.

Conclusions: The PBT might be one of options for patients with liver metastasis of gastric cancer.


Proton and carbon ion radiotherapy for locally advanced pancreatic carcinoma: A preliminary report

Z. Yu1, W. Zheng1, L. Lien-Chun2, H. Zhengshan1, Z. Qing1, L. Jiade1, J. Guoliang1

1Shanghai Proton and Heavy Ion Center, Department of Radiation Oncology, Shanghai, China, 2Shanghai Proton and Heavy Ion Center, Department of Radiation Physics, Shanghai, China

Background: To evaluate the clinical outcome of proton and carbon ion radiotherapy (CIRT) for locally advanced pancreatic carcinoma (LAPC).

Methods and Materials: From Jun 2015 to Oct 2018 41 LAPC patients from 3 prospective clinical trials were combined together for this analysis. 16 patents received proton/photon followed by CIRT (proton/photon plus CIRT) with total doses of 46.2GyE to 68.4GyE by 1.8GyE to 3GyE per fraction, and 25 patients, CIRT alone of 51GyE to 62.9GyE by 3.5GyE to 3.7GyE per fraction. The overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) and acute/late toxicities were analyzed.

Results: With a median follow-up of 13.9 months, for all patients, the median survival time was 18.2 months, and OS, LPFS, PFS and DMFS at 12-month and 18-month were 82.5% and 52.4%; 75.5% and 56.8%; 63.4% and 39.5%; 83.1% and 60.7%, respectively. CIRT alone yielded significantly improved LPFS at 18-month as compared to proton/photon plus CIRT (85.9% vs. 33.8%, p=0.025), but no significant differences in OS, PFS and DMFS were observed between proton/photon plus CIRT and CIRT alone. One patient experienced grade 3 gastrointestinal ulceration. No other severe acute or late toxicities were observed.

Conclusion: CIRT alone improved LPFS significantly, as compared to proton/photon plus CIRT. The toxicity of Proton/photon plus CIRT and CIRT alone for LAPC was mild and tolerable.

Clinics: GU, PTC58-0205

Re-irradiation using particle therapy for pelvic recurrence of gynecological cancer

A. Barcellini1, V. Vitolo1, M.R. Fiore1, B. Vischioni1, A. Iannalfi1, S. Ronchi1, E. D'Ippolito1, R. Petrucci1, F. Valvo1, R. Orecchia1,2

1National Center of Oncological Hadrontherapy Fondazione CNAO, Radiation Oncology, Pavia, Italy, 2European Institute of Oncology, Radiation Oncology, Milano, Italy

Introduction: Reirradiation (reRT) of recurring gynecological tumors (RGT) of the pelvic area presents challenges due to the high cumulative dose in normal tissues such as bowel.

Aim: to evaluate safety and efficacy of reRT with particle therapy (PT) for pelvic RGT.

Material and Methods: Between May 2014 and December 2018, 9 patients (pts) with RGT were admitted for PT at CNAO. Pt and treatment characteristics were summarized in Table I. Two patients, with marginal lymph node recurrence, were irradiated with protons up to a total dose of 25 Gy RBE and 51 Gy RBE, respectively. The remaining women underwent to carbon-ion radiotherapy (CIRT) with a median total dose of 50.4 Gy RBE (range: 36-57, median number of fractions: 12). Five patients with pelvic side wall recurrences received surgical spacer placement to keep intestinal tracts apart from the tumor.

Results: All patients completed the planned treatment and no acute toxicities (CTCAE 4.0) G>2 were observed. For the evaluable patients, no G≥ 2 late toxicity was reported. For pts with a follow-up ≥ 3 months, median LC was 7 months (range: 3-13,8), median MFS was 4.2 months (range: 3-14,2) and median OS was 7 months (range: 3-14,2). 1 pt experienced local progression and 4 pts died for systemic progression. Data is still ongoing.

Conclusions: Although the study's limitations, PT showed no severe toxicities for recurrence of gynecological cancers after RT. Further research is required to identify long-term safety and efficacy for a larger number of pts.


Carbon ion radiotherapy in the management of the melanoma of the lower genital tract

A. Barcellini1, V. Vitolo1, M.R. Fiore1, B. Vischioni1, A. Iannalfi1, S. Ronchi1, R. Petrucci1, E. D'Ippolito1, F. Valvo1, R. Orecchia1,2

1National Center of Oncological Hadrontherapy Fondazione CNAO, Radiation Oncology, Pavia, Italy, 2European Institute of Oncology IEO, Radiation Oncology, Milano, Italy

Background: Malignant mucosal melanoma (MMM) has been regarded as radioresistant tumor.

Aim: to report preliminary results with carbon ion radiotherapy (CIRT) for gynecological MMM treated at CNAO.

Patients and Methods: Between 2016 and 2018, 9 patients (pts) were admitted for CIRT. Patient and tumor characteristics are described in Table I. CM and VuM patients were irradiated with up to a total dose of 28 GyRBE in 3 fractions and 68.8 GyRBE in 16 fractions, respectively, to CTV defined as the GTV + uterine cervix and corpus for the CM and GTV + vulva for the VuM. For VaM the small pelvic space including GTV was irradiated with up to a total dose of 38.7-43 GyRBE followed by a GTV boost of up to a total dose of 68.8 GyRBE in 16 fractions. One pt underwent to adjuvant CIRT on the small pelvic space (43 Gy RBE) after radical surgery without lymphadenectomy.

Results: Treatment was well tolerated and no interruption was needed. Acute toxicity was mild. No G≥2 (according to CTCAE 4.0) late toxicities were observed. Overall, for pts with a follow-up≥ 3 months, the median LC was 8.75 months (< for VuM and CM), the median MFS was 5.25 (range: 3-22,83) and the median OS was 7.03 (range: 3-25,83). 3 pts died for systemic progression. Data is still ongoing for the latest enrolled pts.

Conclusions: CIRT is a safe non-invasive option treatment for gynecological MMM. Clinical trial with a longer follow-up and larger series of patients is necessary.


Treatment time and irradiation dose of organs at risk changes using spot deletion operation in prostate cancers

N. Fukumitsu1, T. Hayakawa2, T. Yamashita2, M. Mima1, Y. Demizu1, T. Suzuki3, T. Soejima1

1Kobe proton center, Radiation oncology, Kobe, Japan, 2Kobe proton center, Physics, Kobe, Japan, 3Kobe proton center, Anesthesiology, Kobe, Japan

Purpose: To investigate how long treatment time is reduced and how much irradiation dose of organs at risk if using spot deletion operation in the intensity modulated proton beam therapy (IMPT) planning in prostate cancers.

Methods: Simulation study was performed in 10 prostate cancer patients. After IMPT planning was completed to accomplish dose restriction in our institute, spots were deleted. One method is lower energy spots were automatically deleted step by step (protocol A) and another method is spots which were distant from the prostate gland were manually deleted step by step (protocol B). Dose distribution of the prostate gland was scheduled as 63 Gy(RBE) with 21 fractions. Both methods were continued within the range of clinical target volume irradiated at least 60 Gy(RBE) was 100%. Treatment time and dose distribution of rectum and bladder was examined.

Results: Treatment time reduction was 2.1—17.5 (median 17.7) seconds in protocol A and 6.3—49.2 (24.3) seconds in protocol B. Rectum volume irradiated at least 50 Gy(RBE) increase was 0.04—1.3 (0.4)% in protocol A and -6.3—-0.7 (-3.1)% in protocol B. Bladder volume irradiated at least 50 Gy(RBE) increase was -0.2—0.3 (0.08)% in protocol A and -4.1—-0.9 (-2.5)% in protocol B.

Conclusions: Spots deletion which distant from the prostate gland operation is efficient in the reduction of not only treatment time but also irradiation dose of organs at risk.


Proton therapy for prostate cancer: Favorable outcomes with low toxicity profile

W. Hartsell1, S. Collins2, V. Casablanca1, S. Mihalcik1, E. Brennan2, A. Van Nispen2, A. Corbett3, N. Mohammed1

1Northwestern Medicine Chicago Proton Center, Radiation Oncology, Warrenville, IL, USA, 2Radiation Oncology Consultants, Radiation Oncology, Warrenville, IL, USA, 3Northwestern Medicine Chicago Proton Cneeter, Radiation Oncology, Warrenville, IL, USA

Purpose: To prospectively evaluate outcomes for treatment of prostate cancer at a single institution

Method: We reviewed patients with localized prostate cancer treated definitively at a single institution, from 10/2010 thru 2/2017. Patients were followed prospectively on a multi-institutional trial (Proton Collaborative Group registry trial), with patient and physician reported outcomes. Fiducial markers were used in all patients, with rectal immobilization used for nearly all patients (free rectal water in 385, rectal balloon in 342, and hydrogel interstitial spacer in 220). Median dose was 79.2 Gy(RBE) in 44 fractions, with 102 patients receiving 70 Gy(RBE) in 28 fractions and 51 with SBRT doses of 38 Gy(RBE) in 5 fractions.

Results: 952 patients were treated, 272 with Stage I (AJCC7, low risk), 467 Stage IIA (intermediate risk), 196 Stage IIB (high risk) and 17 Stage III. Median followup is 50 months, with a minimum of 18 months. 32 patients have died, only 5 from prostate cancer. Adverse events have been mostly grade 1-2, with 9 patients with Grade 3 GU toxicity and 4 patients with grade 3 GI toxicity.

Conclusion: Proton beam therapy is an effective and well tolerated treatment for localized prostate cancer.


Gastrointestinal toxicity is significantly less with hydrogel compared to other rectal immobilization techniques

W. Hartsell1, S. Collins2, V. Casablanca1, S. Mihalcik1, N. Mohammed1, P. Lee1, E. Brennan2, A. van Nispen2, A. Corbett1, V. Gondi1

1Northwestern Medicine Chicago Proton Center, Radiation Oncology, Warrenville, IL, USA, 2Radiation Oncology Consultants- Ltd., Radiation Oncology, Warrenville, IL, USA

Background: Rectal toxicity including rectal hemorrhage is a known side effect of radiation therapy for prostate cancer. Interstitial hydrogel provides both rectal immobilization and provides spacing between the prostate and rectum, and should reduce the incidence and severity of rectal toxicity.

Methods: Patients with localized prostate cancer were treated with definitive proton beam therapy at a single institution on a multi-institutional registry protocol (PCG Registry). Patients were treated primarily with lateral fields to a dose of 79.2 Gy(RBE) in 44 fractions (762 patients), 70 Gy(RBE) in 28 fractions (102 patients) or 38 Gy(RBE) in 5 fractions (51 patients), using fiducials and daily stereoscopic imaging for localization. Patients were treated in consecutive cohorts with rectal water (100 cc), rectal balloons (60-90cc) and hydrogel, and followed prospectively for late (>90 days after treatment) adverse events.

Results: 947 patients treated from 10/10 through 2/17, with median follow-up of 4.4 years, minimum 1.5 years. Rectal water (RW) was used in 385 patients, rectal balloons (RB) in 342 patients and hydrogel spacer (HS) in 220 patients. Post-treatment grade 3 toxicity was rare in all groups. The grade >2 overall GI toxicity rate was 14.8% for RW, 17.3% for rectal balloons, but only 2.2% for HS. Grade 2 rectal bleeding of any grade was noted in 10.4% for RW, 12.3% for RB, and 2.2% for HS.

Conclusions: Interstitial hydrogel spacer significantly reduced the post-treatment gastrointestinal toxicities from radiation therapy, including a significantly lower risk of any rectal bleeding.


Dosimetric comparison between CyberKnife and pencil-beam scanning proton therapy in stereotactic ablative radiotherapy for prostate cancer

C.C. Huang1,2, P.J. Chao1,3, Y.S. Liang1, S.H. Lee1, Y.J. Huang1

1Kaohsiung Chang Gung Memorial Hospital, Department of Radiation Oncology, Kaohsiung, Taiwan, 2Chang Gung University- College of Medicine, Graduate Institute of Clinical Medical Sciences, Taoyuan, Taiwan, 3National Kaohsiung University of Science and Technology, Medical Physics and Informatics Laboratory of Electronics Engineering, Kaohsiung, Taiwan

Purpose: To compare dosimetric difference between CyberKnife M6 and pencil-beam scanning proton therapy (PBSPT) in stereotactic ablative radiotherapy (SABR) for prostate cancer.

Materials and Methods: Four CyberKnife plans from patients with prostate cancer treated by the same radiation oncologist were selected. Their DICOM images of computed tomography-simulation were used for PBSPT plans with single-field optimization of opposed lateral fields. The patient preparation, prescribed dose and constraints in CyberKnife plans followed the protocol of RTOG 0938 trial, and those in PBSPT plans mostly followed the protocol of PCG-GU002-10 trial but lacking rectal balloon and prescribing the same dose with CyberKnife plans (36.25Gy in 5 fractions). We compared the dosimetry of planning target volume (PTV), rectum, bladder and urethra.

Results: The PBSPT plans had significantly lower conformal index (1.08 vs 1.31, p=0.031), new conformal index (1.14 vs 1.33, p=0.047), maximum and mean doses in PTV (37.71Gy vs 40.89Gy, p=0.034; 37.21Gy vs 38.19Gy, p=0.027), dose of 95% PTV volume (99.86% vs 101.18%, p=0.016), and volumes of 105% and 100% prescribed dose in PTV (0% vs 52.98%, p=0.013; 94.52% vs 98.55%, p=0.007). There was no significant difference of dosimetry in rectum. The PBSPT plans had lower mean dose in bladder and maximum dose in urethra but had larger volumes of 95%, 90% and 80% prescribed dose in bladder.

Conclusion: The PBSPT plans had better conformality and homogeneity, lower mean dose in bladder and maximum dose in urethra, but worse PTV coverage by 100% prescribed dose and larger volumes of high percentage-prescribed dose in bladder.


Proton vs. carbon ion radiation therapy: A retrospective study of prostate cancer treatments at the Heidelberg Ion-Beam Therapy Center

S. Mein1, B. Kopp2, K. Choi3, T. Haberer4, J. Debus5, A. Abdollahi6, A. Mairani4

1DKFZ/HIT, Translational Radiation Oncology, Heidelberg, Germany, 2University Hospital Heidelberg, Radiation Oncology, Heidelberg, Germany, 3National Center of Oncological Hadrontherapy CNAO, Medical Physics, Pavia, Italy, 4Heidelberg Ion-Beam Therapy Center HIT, Department of Radiation Oncology, Heidelberg, Germany, 5University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg, Germany, 6German Cancer Research Center DKFZ, Translational Radiation Oncology, Heidelberg, Germany

The Heidelberg Ion Therapy Center (HIT) opened its doors in 2009, treating nearly 400 patients with either proton or carbon ion beams to combat prostate cancer-related disease. Since then, several treatment regimens were applied differing in fractionation scheme and tissue radio-sensitivity factor (α/βratio), used in the local effect model (LEM) during biological dose optimization for carbon ion treatments. With nearly a decade of clinical indication, what have we learned about relative biological effectiveness (RBE) for proton and carbon ion beams and the impact of physical and biophysical parameters on treatment outcome?

In this work, the first HIT prostate patient cohort from the prospective randomized phase 2 clinical trial (Ion Prostate Irradiation, IPI) was collected to study biological effect in context of tumor control. The 92 IPI patients received either proton or carbon ion therapy with identical fraction regime and prescription dose in the target, a total dose of 66 GyRBE administered in 20 fractions. Forward calculations yielding physical dose, dose-averaged linear energy transfer (LETd) and effective dose (applying LEM-IV) are performed using HIT's fast dose engine FRoG (Fast dose Recalculation on GPU) developed in-house. For improved prediction of actual delivered dose, computation is performed using the original planning CT as well as weekly control CTs to account for anatomical changes throughout the treatment course (Fig. 1). Biophysical uncertainty in prostate cancer treatment planning and delivery is investigated to assess clinical efficacy of the two particle therapy modalities.


Hydrogel spacer injections for prostate cancer patients undergoing proton beam therapy

H. Ogino1, H. Iwata1, S. Hashimoto1, K. Nakajima1, Y. Hattori1, K. Nomura1, Y. Shibamoto2

1Nagoya Proton Therapy Center / Nagoya City University, Radiation oncology, Nagoya, Japan, 2Nagoya City University, Radiology, Nagoya, Japan

Background: Various studies have evaluated the efficacy of hydrogel spacer in prostate cancer treatment and have demonstrated that hydrogel spacer is useful and safe. Meanwhile, various anesthetic techniques are used for its injection, and the related pain, regarded as an associated problem, has not been studied in detail.

Methods: This survey was conducted on 200 prostate cancer patients who received hydrogel spacer injections. After local anesthesia was applied to the perineum (20 mL of 1% lidocaine), a gold marker each was placed with a 22-gauge needle via the transperineal approach. Then, the fat between the prostate and rectum was punctured with an 18-gauge needle, and hydrodissection was performed using physiological saline; this was followed by an injection of 10 mL of hydrogel spacer composed of polyethylene glycol. Immediately after completion of the procedure, the degree of the pain severity was rated on pain scales and recorded by the patients themselves. The numerical pain scale (0-10) was used to assess pain severity.

Results: Hydrogel spacer injections were successfully administered to all 200 patients. The median and mean pain scores were 5 and 5.2. At completion of the procedure, hypotension due to vagal reflex was observed in 10 patients. In all these patients, blood pressure recovered after only a few minutes of rest.

Conclusion: Although hydrogel spacer injection before proton beam therapy for prostate cancer is a safe procedure, it often causes moderate pain that lasts for a short period of time.


The role of 99mTc-labeled PSMA-SPECT/CT and mfMRI in the prediction of early response after carbon ion therapy for prostate cancer

P. Li1, C. Liu2, S. Wu1, L. Deng3, G. Zhang1, Q. Zhang1, S. Fu1

1Shanghai Proton and Heavy Ion Center, Department of Radiation Oncology, Shanghai, China, 2Shanghai Proton and Heavy Ion Center, Department of Nuclear medicine, Shanghai, China, 3Shanghai Proton and Heavy Ion Center, Department of Radiology, Shanghai, China

Purpose: The purpose of this study was to assess the predictive value of 99mTc-labeled PSMA-SPECT/CT and Apparent Diffusion Coefficient of MRI for predicting treatment response after carbon ion therapy in prostate cancer.

Methods and Materials: A total of 26 patients underwent 99mTc-labeled PSMA-SPECT/CT and multi-parametric MRI before and after carbon ion therapy. The mean apparent diffusion coefficient (ADCmean) and tumor/background ratio (TBR) were measured on the tumor and the percentage changes between 2 time points (ΔADCmean and ΔTBR) were calculated. Based on follow up clinical examinations, patients were divided into two groups: good response (PSA level < 0.2ng/ml after 6-month treatment) and poor response (PSA level ≥0.2ng/ml after 6-month treatment).

Results: The median follow up time is 27.9 months. The ADCmean was significantly increased compared with the pretreatment value(p< 0.001), while the TBR was significantly decreased compared with the pretreatment value(p=0.001). The ΔADCmean and ΔTBR were negatively correlated with each other (Spearman correlation coefficient, -0.586; p = 0.002 ). On ROC curve analysis for predicting treatment response, the area under the ROC curve (AUC) of ΔTBR (0.867, 95% confidence interval [CI], 0.686, 1.000) for predicting good response was higher than than ΔADCmean (0.819, 95% confidence interval [CI], 0.631, 1.000). The optimal critical for distinguishing good response from poor response in the ROC analysis were ΔTBR ≤ -25.5% and ΔADCmean > 59.9%, respectively.

Conclusions: Our preliminary data indicate that the changes of ADCmean and TBR maybe an early bio-marker for predicting prognosis after carbon ion therapy in patients with prostate cancer.


The adverse events of carbon ion radiotherapy with different segmentations for prostate cancer in China: From 23/24 to 16 fractions

Z. Yang1, S. Fu2

1Fudan University Shanghai Cancer Center FUSCC/Shanghai Proton and Heavy Ion Center SPHIC, Radiation Oncology Dept, Shanghai, China, 2Fudan University Shanghai Cancer Center FUSCC/Shanghai Proton and Heavy Ion Center SPHIC- Shanghai Concord Cancer Hospital, Radiation Oncology Dept, Shanghai, China

Purpose: To assess the effects of two different dose fractionation regimens on radiation toxicity and biochemical control in prostate cancer treated with carbon ion radiotherapy (CIR).

Materials and Methods: A total of 94 prostate cancer patients treated with CIR between June 2014 and March 2018 were analyzed. The incidence of adverse events was assessed based on the Common Terminology Criteria for Adverse

Events version 4.0. Biochemical failure was analyzed, based on Phoenix definition (nadir+2.0ng/ml) in the patient subgroups that received each dose fractionation.

Results: Grade 1 morbidities of the genitourinary (GU) system in 23/24-Fx and in 16-Fx patients were observed in 16 (43.24%) and 8 (14.04%) patients, respectively, while grade 2 (G2) morbidities of the GU were observed in 3 (8.11%) and 9 (15.97%) patients, respectively. No>G2 GU toxicities were observed during the follow-up period. The incidence of GU toxicity in patients treated with 16 fractions was lower than that in patients treated with 23/24 fractions(P=0.03). Grade 1 rectal haemorrhage occurred with 23/24-Fx and with 16-Fx in 2 patients (5.41%) patients and 1 patient (1.75%), respectively. No ≥G2 rectal toxicities were observed. Rectal toxicities did not differ significantly between 23/24-Fx and 16-Fx. There was no significant difference in biochemical failures between 16 Fx(0 patients) and 23/24-Fx (3 patients; 2 were diagnosed with pathologies) (P=0.56).

Conclusion: CIR of 59.2/60.8 GyE in 16-Fx may reduce the incidence of genitourinary toxicity compared with 23/24-Fx. CIR hypofractionation regimens for prostate cancer were considered feasible. An analysis of long-term outcomes is warranted.


Preliminary exploration of clinical factors affecting acute toxicity and quality of life after carbon-ion therapy for prostate cancer

Y. Zhang1, P. Li1, S. Fu2

1Shanghai Proton and Heavy Ion Center-Fudan University Cancer Hospital, Department of Radiation Oncology, Shanghai, China, 2Concord Medical Services Holdings Limited- China, Radiation Oncology Center, Shanghai, China

Purpose: To present acute toxicity and quality-of-life after carbon ion radiotherapy (CIRT) in the Shanghai Proton and Heavy Ion Center (SPHIC) and identify the clinical factors that influenced urinary, bowel, sexual and hormonal function.

Methods: Sixty-four patients with prostate cancer admitted from July 2015 to January 2018 received locoregionally CIRT. At baseline and 5 time-points after radiotherapy, we assessed patients' quality-of-life using the EPIC-26 Chinese version. Logistic regression was performed to identify the clinical factors associated with acute GU toxicity and quality-of-life.

Results: There were 13(20.3%) Grade 1 and 7(10.9%) Grade 2 acute GU events, as well as 2 (3.1%) cases of Grade 1 acute GI toxicity in all. Urinary irritative/obstruction quality-of-life had temporary declines at the end of CIRT (-7.92±1.76, p<0.001). And bowel QOL had a clinically relevant decline at 2 years follow-up. As for urinary incontinence and sexual domain, the quality of life remained stable all the time within 2 years after CIRT. TURP was a risk factor that predicted a decline in urinary related quality-of-life. Age made a difference to bowel quality-of-life. As for sexual quality-of-life, castration status was a remarkable risk factor. IPSS≥8 increased 5.3-fold risk of Grade 1-2 acute GU toxicity. 66 GyE/24Fx had higher occurrence of GU toxicity than 59.2 GyE/16Fx, and bladder's DVH parameters might account for this.

Conclusion: Treated with carbon-ion radiotherapy, prostate cancer patients had low acute radiation-related toxicity and superior quality-of-life. Several clinical factors were found to be related to quality-of-life declines and acute GU toxicity.

Clinics: Sarcoma - Lymphoma, PTC58-0055

First-in-human phase I study of space modulated particle therapy using bioabsorbable spacer

Y. Demizu1, R. Sasaki2, T. Yamashita3, T. Okimoto4, H. Akasaka2, D. Miyawaki2, K. Yoshida2, T. Wang2, S. Komatsu5, T. Fukumoto5

1Hyogo Ion Beam Medical Center Kobe Proton Center, Radiation Oncology, Kobe, Japan, 2Kobe University Graduate School of Medicine, Radiation Oncology, Kobe, Japan, 3Hyogo Ion Beam Medical Center Kobe Proton Center, Radiation Physics, Kobe, Japan, 4Hyogo Ion Beam Medical Center, Radiology, Tatsuno, Japan, 5Kobe University Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery, Kobe, Japan

Background: Surgical spacer placement (SSP) is useful in particle therapy (PT) for patients with abdominal or pelvic tumor adjacent to the intestines. We have developed bioabsorbable spacer which degrades by hydrolysis. We conducted a first-in-human phase I study of the combination of SSP and PT (space modulated particle therapy) using bioabsorbable spacer.

Methods: Eligibility criteria included histologically proven abdominal or pelvic tumor adjacent to the intestines, no metastasis, and no previous radiotherapy. Periodic CT images were obtained before SSP and before/during/after PT (until the spacer disappeared). Treatment planning was performed for each CT image set (until the end of PT) and doses for PTV and OARs were analyzed. Thickness of the spacer was measured for each CT image set. Adverse events were evaluated according to CTCAE v4.0.

Results: Five patients were enrolled in this study. Three patients had sacral chordoma, 1 patient had sacral MPNST, and 1 patient had retroperitoneal leiomyosarcoma. All patients received 70.4 Gy (RBE) (proton therapy in 3 and carbon ion therapy in 2). V95% of PTV before SSP, at the beginning of PT, and at the end of PT was 82.1±11.3%, 98.1±1.1%, and 97.1±0.8%, respectively. The spacers maintained enough thickness (≥1 cm) at the end of PT and disappeared within 8 months after SSP in all patients. No ≥grade 3 adverse events were observed.

Conclusions: SSP using bioabsorbable spacer was useful and safe in PT for abdominal or pelvic tumors adjacent to the intestines. Larger prospective studies with a longer follow-up are warranted.


Carbon ion radiotherapy for extracranial chordoma or chondrosarcoma: Initial experience from Shanghai Proton and Heavy Ion Center

P. Li1, W. Shuang1, C. Xin1, H. zhengshan1, Z. Qing1, F. Shen1

1Shanghai Proton and Heavy Ion Center, Department of Radiation Oncology, Shanghai, China

Particle therapy, especially carbon ion radiotherapy (CIRT) is deemed to be a promising treatment for chordoma and chondrosarcoma. We retrospectively analyzed the outcomes of patients with extracranial chordoma or chondrosarcoma treated by CIRT at Shanghai Proton and Heavy Ion Center to evaluate the efficacy and safety of this promising treatment method. Between May 2015 and April 2018, 21 consecutive patients with chordoma (n=16) or chondrosarcoma (n=5) treated by CIRT were enrolled. Local control (LC), progression free survival (PFS) and overall survival (OS) rates were estimated through the Kaplan-Meier method. The association between each of the candidate prognostic factors and the estimated LC, PFS or OS was tested with the log rank test. The median gross tumor volume (GTV) was 512.7 ml (range, 142.6-2893.0 ml). The median prescription dose was 69 gray equivalent (GyE) (range, 57–80 GyE). After a median follow-up of 21.8 months (range, 7.2-39.2 months), the 1-year LC, PFS and OS were 93.8%, 88.4% and 100%, respectively, whereas the 2-year LC, PFS and OS were 85.2%, 80.4%, 100%, respectively. Univariate analysis revealed that age, mental implant status, treatment status, sex, dose, and GTV were not significant prognostic factors for LC, PFS or OS. No grade 2 or higher early and late toxicities were observed within follow-up. CIRT can provide efficient tumor control for patients with extracranial chordoma or chondrosarcoma. Long-term results deserve further investigation, even in a prospective randomized trial.


Proton therapy for cardiac sarcoma: A two-case series describing the clinical and dosimetric advantages of proton-based therapy

N. Vorobyov1, G. Andreev2, N. Martynova1, A. Lyubinsky2, A. Kubasov2

1Sergey Berezin Medical Center, Radiation Oncology, Saint-Petersburg, Russian Federation, 2Sergey Berezin Medical Center, Medical Physics, Saint-Petersburg, Russian Federation

Cardiac sarcomas are extremely rare neoplasms with an aggressive behavior. Surgery is the most accepted treatment modality, but total resection is rarely achievable without causing fatal damage to the heart. The purpose of this study was to describe our experience implementing intensity modulated proton therapy (IMPT) for cardiac sarcomas.

We present two patients who received IMPT. The first patient was 55-year-old woman with pleomorphic sarcoma of right ventricle, spreading to pulmonary valve, tricuspid valve and ventricular septum with metastatic spread to mediastinal lymph nodes. The GTV was treated to 66 Gy in 2,2 Gy per fraction. The CTV, including affected mediastinal lymph nodes was irradiated to 60 Gy, using simultaneously integrated boost technique.

The second patient was a 15-year-old boy with pericardial Ewing sarcoma. The CTV was irradiated to 55,8 Gy.

CT scans, MRI scans and treatment were made using respiratory gating at end expiration.

The follow-up period for the first patient is 3 months and for the second patient 4 months. There was no any acute toxicity during treatment and follow-up. CT and MRI scans three months post-radiation demonstrated tumor shrinkage in both cases.

In order to compare dose values, IMRT photon-based plans were generated. IMPT produced lower mean lung dose, lung V5 and V20, heart V40, and dose to contralateral lung than did IMRT.

IMPT in combination with respiratory motion tracking appears to be a technically feasible and clinically well-tolerated local control modality for cardiac sarcomas, providing limited exposure to organs at risk in comparison with IMRT photon plans.

Clinics: GI / Sarcoma Poster Discussion Sessions, PTC58-0371

Preliminary clinical observation of particle radiotherapy for 20 cases of thymic malignancies and dosimetric comparison between photon and particle plans

J. Chen1, N. Ma1, Y. Lu2, J. Zhao3, K. Shahnazi2, J. Lu1, G. Jiang4, J. Mao4

1Shanghai Proton and Heavy Ion Center, Radiation Oncology, Shanghai, China, 2Shanghai Proton and Heavy Ion Center, Medical Physics, Shanghai, China, 3Shanghai Proton and Heavy Ion Center- Fudan University Shanghai Cancer Center- Fudan University, Medical Physics, Shanghai, China, 4Shanghai Proton and Heavy Ion Center- Fudan University Shanghai Cancer Center- Fudan University, Radiation Oncology, Shanghai, China

Objective: To evaluate the safety and efficacy of particle therapy (PT) for thymic malignancies, and to compare dose distribution between photon versus particle radiotherapy.

Methods: From 09/2015 to 08/2018, 20 patients with thymic malignancies (stage I-IVB) who were treated with PT using pencil beam scanning technique and≥1 time of follow-up were enrolled. The median maximum diameter was 6.1 (2.7-17.7) cm for the 14 patients with gross tumors. Prescriptions of proton 44-48.4GyE/20-22 fractions with carbon ion boost 21-23.1GyE/7 fractions were administered to patients with gross tumor except one palliative treatment, proton 45-61.6GyE/25-30 fractions to patient after R0/R1 resection, and carbon ion 60GyE/20 fractions for re-irradiation. Dosimetric comparisons were conducted in patients with gross tumors using the same total dose of 66Gy(E).

Results: The median follow up time is 12.6 (2.4-36.3) months. Only one local recurrence was observed (6.8 months after start of treatment) in the palliatively-treated patient who had huge lesion after failure of multiple regimens of chemotherapy. Regional lymph node, pleural or distant metastasis occurred in 3 patients 6.1∼22.8 months after treatment. One patient developed a second primary cancer confirmed by histological pathology 13.7 months after the start of treatment. Except one myocardial infarction (grade 4 late toxicity), no other toxicities ≥grade 3 were observed. Compared with photon, particle plans could significantly reduce the doses to lungs, heart, esophagus and spinal cord.

Conclusion: PT was safe and effective for patients with thymic malignancies after short-time follow-up, and has significant advantages over photon in sparing organs at risk.


Clinical outcome of sacral chordoma patients treated with pencil beam scanning proton therapy

M. Walser1, B. Bojaxhiu1, S. Kawashiro1, S. Tran1, A. Pica1, B. Bachtiary1, D. Weber1

1PSI, Center for Proton Therapy, Villigen, Switzerland

Purpose: To analyze tumor control and toxicity in sacral chordoma patients treated with definitive or postoperative pencil beam scanning (PBS) proton therapy (PT).

Methods and Materials: Sixty patients with histologically proven sacral chordoma treated between November 1997 and October 2009 at the Paul Scherrer Institute either by postoperative (n=50) or definitive PT (n=10) were retrospectively analyzed. Survival rates were calculated using the Kaplan-Meier actuarial method. The log-rank test was used to compare different functions for local control (LC), freedom from distant recurrence (FFDR) and overall survival (OS). Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events v5.0.

Results: Median follow-up was 48 months (range, 4-186). Local recurrence occurred in 20 (33%) patients. At 4 years, LC, FFDR, and OS rates were 77%, 89%, and 85%, respectively. In univariate analysis, subtotal resection (P=0.02) and gross tumor volume > 130 ml (P=0.04) were significant predictors for local recurrence. Twenty-four (40%), 28 (47%), 8 (11%) patients experienced acute Grade 1, Grade 2, and G3, respectively. Grade 2 and 3 late toxicity was observed in 27 (45%) and 9 (15%). No grade 4-5 late toxicity was observed.

Conclusion: Our data indicate that PBSPT is both safe and effective. Subtotal resection and gross tumor volume are prognostic factors for local tumor control.


Acute and late skin toxicity assessment in paediatric/young adult patients with Ewing's sarcomas treated with chemo-radiotherapy

S. Gaito1, A. Abravan2, J. Richardson3, M. Clarke3, R. Colaco1, M. Lowe3, E. Smith1, D. Saunders1, B. Brennan4

1The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom, 2The University of Manchester, Radiotherapy Related Research, Manchester, United Kingdom, 3The Christie NHS Foundation Trust, Medical Physics and Engineering, Manchester, United Kingdom, 4Royal Manchester Children's Hospital, Paediatric Oncology, Manchester, United Kingdom

Purpose: To assess skin toxicity for paediatric patients/young adults with Ewing's Sarcomas (ES) treated with chemo-radiotherapy.

Materials and Methods: Thirty-four patients with stage I-IV ES in different sites treated between 2010 and 2017 were retrospectively analysed. Eleven patients received Proton Beam Therapy (PBT) within the “Overseas Program” and 23 external radiotherapy with Photons (XRT) at the Christie. Median age at diagnosis was 15.5 years (4–25). All patients received chemotherapy regimens containing Doxorubicin or Actinomycin D (figure1). Radiotherapy doses were given in 1.8 Gy per fraction in various total doses (45, 50.4, 54 and 59.4 Gy). Acute and late toxicities were recorded using RTOG/EORTC scoring system.

Results: The risk of developing acute (grade 1 versus higher than grade 1) and late (grade 0 versus grade non-zero) skin toxicities was measured against known clinical factors by employing logistic regression. There were no significant differences on developing acute/late skin toxicities based on different primary sites of the disease or between PBT and XRT groups. Moreover, risk of developing acute/late skin toxicity didn't associate with chemotherapy regimens. No correlation was found between the severity of acute/late toxicity and total dose. However, risk of developing late skin toxicity was significantly higher for patients treated with surgery (p=0.02).

Conclusions: No differences in terms of skin toxicity was found for patients treated with chemo-radiotherapy using either PBT or XRT. Associations between dosimetric parameters and skin toxicity will be considered in the future.


Early experience with protons for chordomas of the sacrum and mobile spine

I. Petersen1, S. Ahmed1, N. Laack1

1Mayo Clinic, Radiation Oncology, Rochester, MN, USA

Background: We report on our early experience with pencil beam scanning proton radiotherapy for chordomas of mobile spine and sacrum.

Methods: Retrospective review of 31 patients treated between June 2015 and January 2019. The mean age was 59 (range 22-88) with 22 men. Records were reviewed for tumor outcomes and toxicity.

Results: Sixteen tumors were sacrococcygeal and 15 were mobile spine including 6 cervical, 3 thoracic, and 6 lumbar. Twelve sacrococcygeal tumors had definitive radiation with a median dose of 69.6 Gy RBE1.1 in 30 fractions (73.8 Gy3 EQD2). The median size of sacral tumors was 7.6 cm (range 2.6 – 16) with 8 patients having disease extending to S1 or S2. All but two patients with mobile spine lesions underwent surgery with 3 having an en bloc resections in combination with radiation and 10 had partial or piecemeal resections, most of these having surgery elsewhere before presenting to our institution. Two patients also received a dural P-32 plaque treatment at the time of resection. Three of the spine patients were treated with a component of photon therapy in a preoperative setting prior to surgical resection. With a median follow-up 13.3 months (0-37.7), all patients except one who sustained a compression fracture and biopsy at the time of vertobroplasty revealing active disease are locally controlled. No myelopathy has been reported. Data on acute complications and other outcome data will be presented.

Conclusions: Early results of pencil beam scanning treatment for chordoma of mobile spine are promising and consistent with expected outcomes.


S-1 and concurrent image-guided proton therapy for unresectable locally advanced pancreatic cancer: An interim report of phase II study

K. Nakajima1,2, Y. Hattori1, H. Iwata1,2, S. Hashimoto1,2, J.E. Mizoe3, H. Ogino1,2, Y. Shibamoto2

1Nagoya Proton Therapy Center- Nagoya City West Medical Center, Department of Radiation Oncology, Nagoya, Japan, 2Nagoya City University Graduate School of Medical Sciences, Department of Radiology, Nagoya, Japan, 3Osaka Heavy Ion Therapy Center, Department of Radiation Oncology, Osaka, Japan

Background: We designed single-institutional prospective phase II trial to assess the efficacy and safety of chemo-proton therapy (CCPT) with image-guided proton therapy (IGPT) for unresectable locally advanced pancreatic cancer (LAPC). The present study reports the interim results of the trial.

Materials and Methods: Between February 2015 and March 2018, 22 patents with unresectable LAPC received CCPT followed by adjuvant chemotherapy. Metallic markers were used for image guidance using a respiratory-gated imaging technique. Proton therapy with 60 GyE/ 20 Fr was delivered to the GTV and 40 GyE/20 Fr to the CTV, using a field-in-field technique. Patients received concurrent and adjuvant S-1 chemotherapy. Toxicities were evaluated according to CTCAE version 4.0.

Results: Median patient age was 72 years (range; 50-79) and the male: female ratio was 10:12. Eleven patients had a pancreatic head tumor. Three had positive lymph nodes. All patients completed CCPT plus adjuvant chemotherapy. The median follow-up was 14 months. Local control (LC) and overall survival (OS) rates at 1-year were 100% and 81%, respectively and 2-year were 89% and 34%, respectively. The median OS was 19 months. Acute grade 3 toxicities observed were anemia in 4 patients (18%) and anorexia in 2 patients (9%) and grade 2 were gastric ulcer in 2 patients (9%). Chronic grade 3 was anemia in 3 patients (14%).

Conclusions: CCPT with our protocol for unresectable LAPC was generally well tolerated without patients uncompleted the treatments. It appeared to offer good LC. Further investigation with a larger number of patients is warranted.


Two-years clinical experience of the carbon-ion pencil-beam fast rescanning for the treatment of hepatocellular carcinoma

T. Iizumi1,2, S. Minohara2, Y. Kusano2, Y. Matsuzaki2, K. Tsuchida2, I. Serizawa2, D. Yoshida2, H. Katoh2, H. Sakurai1, H. Tujii2

1University of Tsukuba, Department of Radiation Oncology and Proton Medical Research Center PMRC, Tsukuba, Japan, 2Kanagawa Cancer Center, Department of Radiation Oncology and Ion-beam Radiation Oncology Center i-ROCK, Kanagawa, Japan

Purpose: In November 2016, our center started carbon-ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC), which has respiratory motion. The feature of our CIRT is the combination of carbon-ion pencil-beam fast rescanning (CI-PBFR) and the gating with a respiratory sensor to overcome interplay-caused inhomogeneous dose distribution. We reviewed clinical outcomes of HCC patients treated by this distinctive method at our center.

Methods: Between November 2016 and December 2017, 27 patients with HCC were treated with the combination of CI-PBFR and the gating with a respiratory sensor. All patients were treated at a total dose of 60 Gy (RBE) in 4 fractions. Overall survival (OS) and local control (LC) were estimated by Kaplan-Meier method. Adverse Events (AE) were evaluated according to Common Toxicity Criteria for AE version 4.

Results: Median follow-up time was 15.5 months (range, 3.0 to 24.3 months) from the start of CIRT. Mean age was 74 (range, 63 - 92). Twenty-five patients (92.6%) were Child-Pugh class A and two patients (7.4%) were class B. Mean tumor size was 3.8 cm (range, 1.0 - 11.2) in diameter. 1-year OS and LC were 92.1% and 95.5%, respectively. Grade 3 AE was observed in two patients (7.4%): increased transaminase and pleural effusion. Grade 4 or higher AE was not observed.

Conclusion: The combination treatment of CI-PBFR and the gating with a respiratory sensor was feasible for HCC, which has respiratory motion. This method is a promising high precision therapy with tolerability and effectiveness for HCC.


The effectiveness and role of risk-adapted proton beam therapy for hepatocellular carcinoma

T.H. Kim1, J.W. Park2, K. Bo Hyun2, K. Hyunjung1, M. Sung Ho1, K. Sang Soo1, W. Sang Myung2, K. Young-Hwan2, L. Woo Jin2, K. Dae Yong1

1National Cancer Center, Center for Proton Therapy, Goyang, Korea Republic of, 2National Cancer Center, Center for Liver Cancer, Goyang, Korea Republic of

Purpose: To evaluate the effectiveness and role of risk-adapted proton beam therapy (PBT) in patients with hepatocellular carcinoma (HCC).

Methods and Materials: A total of 243 HCC patients received risk-adapted PBT with three dose-fractionation regimens (regimen A [n=40], B [n=60], and C [n=143]) according to the proximity of their gastrointestinal organs (<1 cm, 1–1.9 cm, and ≥2 cm, respectively): the prescribed doses to planning target volume 1 (PTV1) were 50 GyE (EQD2, 62.5 GyE10), 60 GyE (EQD2, 80 GyE10), and 66 GyE (EQD2, 91.3 GyE10) in 10 fractions, respectively, and those of PTV2 were 30 GyE (EQD2, 32.5 GyE10) in 10 fractions.

Results: In all patients, the 5-year local recurrence-free survival (LRFS) and overall survival (OS) rates were 87.5% and 48.1%, respectively, with grade ≥3 toxicity of 0.4%. In regimens A, B, and C, the 5-year LRFS and OS rates were 54.6%, 94.7%, and 92.4% (p<0.001), and 16.7%, 39.2%, and 67.9% (p<0.001), respectively. The 5-year OS rates of the patients with mUICC stages I, II, III, and IVA and BCLC stages A, B, and C were 69.2%, 65.4%, 43.8%, and 26.6% (p<0.001), respectively and 65.1%, 40%, and 32.2% (p<0.001), respectively. In a multivariate analysis, the Child-Pugh classification, alpha-fetoprotein level, mUICC stage, dose-fractionation regimens, and primary tumor response were independent prognostic factors associated with OS.

Conclusions: PBT could achieve promising long-term tumor control and have a potential role as a complementary or alternative therapeutic option across all stages of HCC.


A preliminary report of a phase I dose escalation study: Scanning carbon ion beam radiation therapy for hepatocellular carcinoma

Z. Hong1, Z. Yu1, Z. Wang1, G. Jiang1

1Shanghai Proton and Heavy Ion Center, Radiation Oncology, Shanghai, China

Purpose: To analyze the dose limiting toxicities (DLTs) in hepatocellular carcinoma (HCC) patients treated with scanning carbon ion beam radiation therapy (SCIRT).

Methods and Materials: Patients diagnosed as HCC, surgical unresectable or refusal to surgery, were treated by SCIRT with 4 dose levels of 55 GyE, 60 GyE, 65 GyE and 70 GyE in 10 fractions, respectively (5 fractions per week). At least 3 patients would be enrolled in each dose level. Once the observation time was less than 3 months for the last enrolled patient in the 2nd to 4th dose level, a new eligible patient would be assigned to the dose level, which was one level lower than that was testing. When >33% of the patients developed DLTs, the dose escalation would be terminated.

Results: From Jan 2016 to July 2018, 23 patients have been enrolled in this study with median diameter of 5.1 cm, 5 in dose of 55GyE, 6 in 60GyE, 9 in 65GyE and 3 in 70GyE. All the patients completed SCIRT and no treatment-related DLTs occurred. For acute toxicities, grade 1-2 of early skin injury, leokocytopenia, neutrocytopenia and thrombocytopenia were observed in 13.1%, 26.1%, 17.4% and 17.4% patients, respectively. None of patients presented treatment-related late toxicities. Median follow-up time was 16.0 months. The 1-and 2-year overall survival rates were 95.2% and 89.9%, and the 2-year local progression-free survival rates were 100%.

Conclusion: SCIRT with treatment dose of 70GyE in 10 fractions is safe for HCC patients, and survival and local control were promising.


Early results of re-irradiation for rectal cancer using pencil-beam scanning proton therapy are promising

A. Koroulakis1, J. Molitoris2, A. Kaiser2, N. Hanna3, Y. Jiang4, W. Regine2

1University of Maryland Medical Center, Radiation Oncology, Baltimore, MD, USA, 2University of Maryland School of Medicine, Radiation Oncology, Baltimore, MD, USA, 3University of Maryland School of Medicine, Surgical Oncology, Baltimore, MD, USA, 4University of Maryland School of Medicine, Medical Oncology, Baltimore, MD, USA

Purpose: Re-irradiation (Re-RT) for rectal cancer (RC) in patients with prior pelvic RT has been shown to be safe and effective. However, limited data exists with the use of proton therapy (PT). We hypothesize that PT is a safe and feasible for re-treatment and may allow for decrease in toxicity or treatment escalation.

Methods and Materials: We performed a single institutional retrospective IRB-approved analysis of all RC patients with any prior pelvic RT re-irradiated with Pencil-Beam Scanning proton therapy (PBSPT). We collected patient and treatment characteristics, including prior diagnosis, re-irradiation records, and toxicities. Outcomes, including overall Survival (OS) and Local Control (LC), were estimated using Kaplan-Meier.

Results: Twenty-three patients (median follow-up 17 months) received PBSPT Re-RT from 2016-2018: 14 patients w/ recurrent RC [median prior dose 50.4 Gy (43.2-63.0)] and 9 patients w/ de novo RC and variable prior RT (8 for prostate, 1 for ovarian). Median Re-RT dose was 48 Gy [(16.0-60.0); 17/23 were treated BID], and 21/23 received concurrent chemotherapy. Four underwent surgical resection (all R0). Three patients experienced grade 3 acute toxicities, and no acute Grade 4-5 toxicities were observed. Two patients had grade 3+ late toxicities, including a grade 5 toxicity occurring in a patient with history of significant injury from prior RT. One-year LC and OS were 83.3% (95% CI 72.1-94.5%) and 77.6% (95% CI 67-88.2%), respectively.

Conclusion: In this largest such series, early results of PT for Re-RT for RC are promising, with longer follow-up needed.


Pathologic complete response (pCR) rates and outcomes after neoadjuvant chemoradiotherapy with proton or photon radiation for distal esophageal adenocarcinoma

C.M. DeCesaris1, J.I. Choi2, S.R. Carr3, W.M. Burrows3, W.F. Regine2, C.B. Simone II2, J. Molitoris2

1University of Maryland Medical Center, Department of Radiation Oncology, Baltimore, MD, USA, 2University of Maryland School of Medicine, Department of Radiation Oncology, Baltimore, MD, USA, 3University of Maryland School of Medicine, Department of Thoracic Surgery, Baltimore, MD, USA

Background: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy is associated with improved survival in patients treated for esophageal cancer. While proton beam therapy (PBT) has demonstrated reduced toxicities, limited reports have evaluated pCR rates between modalities.

Methods: Single-institutional review of patients from 2016-2018 with distal esophageal adenocarcinoma treated with trimodality therapy including PBT was undertaken; patients were compared 2:1 to patients treated in a contemporary timeframe with photons.

Results: Sixteen consecutive proton patients were compared to 32 consecutive photon patients. Overall median follow-up was 20 months. All patients received concurrent chemotherapy with carboplatin/paclitaxel. Median radiation dose in both cohorts was 50.4/1.8Gy (p=0.353). Age, gender and race were well balanced, but patients treated with PBT were more advanced stage (p=0.049) with increased nodal burden (N2: 31% PBT vs. 3.0% photon, p=0.019). Despite this, proton patients achieved an equivalent proportion of nodal clearance (64% PBT vs. 67% photon, p=0.873). pCR rates did not significantly differ between modalities (19% PBT vs. 25% photon, p=0.627).

Two grade 5 perioperative complications occurred in the photon group; no PBT patients experienced a grade 5 event. There were no differences in grade 3/4 toxicities. 18-month survival was comparable between PBT and photon patients (88% CI, 76 to 100 vs. 71% CI, 62 to 80; p=0.288).

Conclusions: The use of PBT in trimodality therapy for distal esophageal adenocarcinoma is safe and yields pCR rates comparable to photon radiation and historical controls. pCR and nodal clearance rates did not significantly differ despite PBT patients having higher AJCC stage and nodal burden.

Clinics: Head and neck, PTC58-0058

BNCT for head and neck cancer: Summary of reactor irradiation

T. Aihara1, J. Hiratsuka2, N. Kamitani2, M. Higashino3, R. Kawata3, H. Kumada4, H. Sakurai4, K. Ono1

1Osaka Medical College, Kansai BNCT Medical Center, Takatsuki, Japan, 2Kawasaki Medical School, Radiation Oncology, Kurashiki, Japan, 3Osaka Medical College, Otolaryngology Head and Neck Surgery, Takatsuki, Japan, 4University of Tsukuba, Proton Medical Research Center, Tsukuba, Japan

Purpose: Boron Neutron Capture Therapy (BNCT) is a form of radiation therapy that utilizes alpha rays from thermal neutron capture of the boron atom. In this report, we summarize our clinical results for BNCT for the treatment of head and neck cancer at our institution.

Methods: We started clinical studies for the treatment of head and neck cancer in 2003. Since then, we have completed the following four clinical studies: (1) an analysis of the accumulation of BPA in the tumor and surrounding normal -tissue using an 18FBPA-PET study, (2) a BNCT clinical trial for recurrent head and neck cancer, (3) a BNCT clinical trial for head and neck melanoma, and (4) a BNCT clinical trial for newly diagnosed advanced head and neck cancer.

Results: The 18FBPA-PET study showed no difference in the T/N ratio between an SCC and a non-SCC group. Overall, 83% of the patients had a T/N ratio of more than 2.5. The response rates were more than 80% for all the BNCT clinical studies. Although mild alopecia, xerostomia, and fatigue were observed in all the patients, no severe adverse effects of grade 3 or higher occurred in these patient series (Fig.1).

Conclusions: Our preliminary results demonstrated that BNCT is a potentially curative therapy for patients with head and neck cancer. The treatment does not cause any serious adverse effects, and can be used regardless of whether the primary tumor has been previously treated.


Intensity-modulated proton therapy reduces acute treatment-related toxicities for patients with nasopharyngeal cancer: A case-control propensity score match study with VMAT

Y.C. Chou1

1Proton and Radiation Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Purpose/Objective(s): To evaluate the differences in the treatment-related toxicity and neutropenia rate between patients with nasopharyngeal cancer treated with IMPT and VMAT.

Materials and Methods: From December 2016 to December 2017, 80 patients receiving IMPT and 80 patients receiving VMAT for nasopharyngeal cancer were propensity score-matched. The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE 4.03) was used for toxicity evaluation. Chi-square test was used in the univariate analysis. Then multivariate logistic regression analysis was used in the multivariate analysis for binary toxicity endpoints.

Results: The median follow-up time was ten months. During treatment, 5 IMPT-treated patients (6.3%) and 13 VMAT-treated patients (16.3%) were suffered from nasogastric tube insertion (OR=0.386, P=0.045). The mean duration of NG-tube placement was 2 and 6.4 weeks in the IMPT and VMAT patients respectively (P=0.318). The patients with body weight loss over 8 % were significantly different between IMPT group 20% and VMAT group 35% (OR=0.571, P=0.034). Of the patients treating with concurrent chemo-radiotherapy, there were significantly less any grade neutropenia adverse events in IMPT group compared with VMAT group (OR=0.324, P=0.023). There were seven patients (10.3%) in IMPT group and twelve patients (17.7%) in VMAT group not receiving cisplatin dose intensity over 200 mg/m2. After allowing potential confounders in multivariate analysis, IMPT treatment retained its independent association with NG-tube insertion and weight loss over 8% (P=0.039).

Conclusion: IMPT is associated with reduced rates of NG-tube insertion, weight loss over 8% and neutropenia adverse events. The result may potentially increase treatment outcome for nasopharyngeal cancer patients treated with IMPT.


Proton therapy boost in locally advanced head and neck cancer: Toxicity and clinical outcome

E. Dippolito1, B. Vischioni1, S. Ronchi1, M. Bonora1, M.R. Fiore1, V. Vitolo1, A. Iannalfi1, R. Petrucci1, F. Valvo2, R. Orecchia3

1National Center of Oncological Hadrontherapy CNAO, Radiation therapy Unit, Pavia, Italy, 2National Center of Oncological Hadrontherapy CNAO, Radiotherapy Unit, Pavia, Italy, 3National Center of Oncological Hadrontherapy CNAO, Scientific Directorate, Pavia, Italy

Purpose: feasibility, acute toxicity and clinical outcome in patients (pts) with LAHNC treated with exclusive sequential mixed beam (MB) approach: IMRT followed by proton therapy (PT) boost

Methods: between July 2012 to January 2018, 41 pts with histologically proven LAHNC (stage III-IV) were treated with MB approach: IMRT of the neck and macroscopic disease followed by PT boost on the pre-treatment macroscopic disease. Tumor sites were: nasopharynx 28 pts (69%), oropharynx 5 pts (12%), larynx 1 patient (2%), sinonasal 4 pts (10%) and oral cavity 3 pts (7%). IMRT prescription dose was 54-60 Gy (elective irradiation of the neck and macroscopic disease), PT prescription dose was 10-20 Gy RBE, for a total dose up to 70-74 Gy RBE. Local control (LC) and toxicity profile (according to CTCAE V4.03- scale) were evaluated.

Results: The median follow-up was 12 months. Treatment was well tolerated, 11 (27%) pts developed G3 acute radiation-related toxicity: 2 pts (5%) mucositis, 1 patient (2%) skin reaction and 5 pts (12%) dysphagia. No pts had high grade (G3-4) late toxicity. LC was 83%. Four pts had local recurrence at 12, 11, 8 and 8 months after treatment, respectively. Three pts developed distant metastases at 6, 18 and 25 months after the end of the treatment. Three pts died for tumor specific-causes.

Conclusions: for pts with LANHC a MB approach was feasible and our results showed good short-term outcome and limited radiation-related side effects. Preliminary results are encouraging but a longer follow-up and large patient accrual are required


Toxicity in patients with locally advanced nasopharyngeal cancer treated with mixed beam (IMRT and proton therapy boost)

E. Dippolito1, D. Alterio2, S. Gandini3, B. Vischioni1, S. Ronchi1, M. Bonora1, R. Petrucci1, B.A. Jereczeck2, F. Valvo1, R. Orecchia4

1National Center of Oncological Hadrontherapy CNAO, Radiotherapy Unit, Pavia, Italy, 2European Institute of Oncology, Radiation therapy Unit, Milano, Italy, 3European Institute of Oncology, Division of Epidemiology and Biostatistics, Milano, Italy, 4National Center of Oncological Hadrontherapy CNAO, Scientific Directorate, Pavia, Italy

Objective: Compare radiation-induced acute toxicity in patients (pts) affected by LANPC treated with sequential IMRT and proton therapy (PT) boost (mixed beam-MB) with an historic cohort of pts treated with IMRT.

Materials and Methods: From June 2012 to November 2017, 27 pts with LANPC (cT3-4) were treated with MB approach: IMRT up to 54-60 Gy followed by PT boost up to 70-74 Gy RBE. This cohort were compared to an historic cohort of 17 pts treated with IMRT only. Pts treated with IMRT only received a total dose of 69.96 Gy. The acute-toxicity profile (worst event) was evaluated according to CTCAE V4.03 scale.

Results: The total dose was significantly higher (p=0.02) in pts treated with MB. G3 mucositis and G2 xerostomia were found in 11% and 76% (p=0.0002) and 7% and 35% (p=0.02) of pts treated with MB and IMRT, respectively. Absorbed dose to acute toxicity-related structures were summarized in Table1. For MB cohort median follow-up was 25 months. All but one pts achieved complete tumor response and no pts developed local/regional recurrences. For IMRT only cohort median follow-up was 51 months. One patient died for treatment-related toxicity. One patient did not achieve a complete tumor response. Three patients experienced tumor local progression; 3 pts experienced also lymph node recurrences/metastasis.

Conclusions: Our results suggest that sequential MB approach for locally advanced NPC pts is safe with an excellent acute toxicity profile. Preliminary results on clinical outcome are encouraging but need to be confirmed in lager cohort of pts.


Proton therapy for head and neck cancer – how much actual evidence is there for benefit? A ‘devil's advocate’ view

C. Kelly1, C. Dobeson2, S. Iqbal2, S. Chatterjee3

1Northern Center for Cancer Care, Freeman Hospital, Newcastle upon Tyne, United Kingdom, 2, United Kingdom, 3Tata Hospital, India

There is only a limited literature in the use of proton or carbon ion therapy in head and neck cancer (HNC) and this has dealt mainly with addressing the physics and dosimetric challenges involved and optimization of both proton and carbon ion delivery and optimizing patient selection. There have been less than 30 papers in the literature in the last five years, dealing with the clinical use, outcomes and benefits of proton therapy in head and neck cancer, when compared to intensity modulated radiotherapy or arc techniques..

Past literature reviews have emphasized the potential for proton therapy, but the use of protons to boost photon therapy in earlier protocols, and the paucity of prospective randomized controlled trials in HNC, (an exception, the NCT0189 3307 prospective trial, but with no results until after 2023), give a mixed and imprecise view of proven outcome benefits for the use of protons or carbon ions, in the common head and neck cancers.

This presentation summarizes the positive clinical outcomes, described for HNC, treated with proton or carbon ion therapy, and illustrates which subsites may benefit most with proton treatment from the present literature, and, as importantly show where there is no positive data. With the development of the UK proton service, some HNC patients will have considerable distances to travel to access these innovative treatments, and it is important to describe the evidence base, showing which patients may benefit, and how, depending on specific HNC subsites and be aware where there is no evidence of outcome benefit.


Inter-fraction robustness of intensity-modulated proton therapy in the treatment of post-operative oropharyngeal squamous cell carcinomas

C. Hague1, T. Li2, A. Lin2, M. Lowe3, J. Lukens2, N. Slevin1, D. Thomson1, M. van Herk4, C. West5, K. Teo2

1The Christie NHS Foundation Trust, Department of Head and Neck- Clinical Oncology, Manchester, United Kingdom, 2University of Pennsylvania, Department of Radiation Oncology, Philadelphia, PA, USA, 3The Christie NHS Foundation Trust, Christie Medical Physics and Engineering, Manchester, United Kingdom, 4Division of Cancer Sciences- School of Medical Sciences- Faculty of Biology Medicine and Health- Manchester Academic Health Sciences Center- University of Manchester-The Christie NHS Foundation Trust, Department of Radiotherapy Related Research, Manchester, United Kingdom, 5Division of Cancer Sciences- Manchester Academic Health Science Center- University of Manchester- The Christie NHS Foundation Trust- UK, Translational Radiobiology Group, Manchester, United Kingdom

Purpose: To evaluate dosimetric consequences of inter-fraction set up variation and anatomical changes in patients receiving multi-field optimised (MFO) intensity modulated proton therapy for post-operative oropharyngeal cancers.

Methods: Six patients treated with proton beam therapy for postoperative oropharyngeal cancer were evaluated. Plans were optimised to clinical target volumes (CTVs) with parameters of 3 mm setup and 3.5% range uncertainty. Each patient underwent weekly online cone-beam computed tomography (CBCT). Planning CT was deformed to the CBCT to create virtual CTs (vCTs) on which the planned dose was recalculated. vCT plan robustness evaluation was evaluated using a set up uncertainty of 1.5 mm and range uncertainty of 3.5%. Target coverage, D95%, and hotspots D0.03cc, were evaluated for each uncertainty along with the nominal, error-free, plan. Mean dose to organs at risk (OAR) for the nominal plan and relative % change in weight from baseline were evaluated.

Results: Robustly optimized plans in post-operative oropharyngeal patients using a single CT scan are robust against inter-fraction set up variations and range uncertainty. Max D0.03cc in the nominal plans were clinically acceptable across all plans. No patients lost ≥10% weight from baseline, Figure 1. Mean dose to the ipsilateral parotid gland, oral cavity, larynx, pharyngeal constrictor muscles and max dose to the spinal cord remained within tolerance, Figure 2.

Conclusion: MFO plans in post-operative oropharyngeal patients were robust to inter-fraction uncertainties in set up and range in regard to CTV coverage. A robust analysis protocol for MFO plans will improve consistent reporting and plan evaluation amongst radiotherapy centers.


A comparison of physician and patient reported outcomes in the elderly head and neck cancer population: IMPT vs. IMRT

E. Jeans1, G. Manzar1, D. Routman1, S. Patel2, D. Ma1, S. Lester1, R. Foote1

1Mayo Clinic, Department of Radiation Oncology, Rochester, MN, USA, 2Mayo Clinic, Department of Radiation Oncology, Phoenix, AZ, USA

Dosimetric comparison of head and neck radiation plans between intensity modulated radiotherapy (IMRT) and intensity modulated proton therapy (IMPT) demonstrates superior non-target tissue sparing with the use of IMPT. Retrospectively, we aim to investigate the dosimetric advantage of IMPT in regards to improved treatment tolerance in an elderly cohort.

We analyzed outcomes for patients receiving curative-intent radiotherapy, age 65 years and older. Outcomes included patient-reported outcomes (PRO) of side effects and physician-reported toxicities. Patients must have completed at least a baseline and one post-treatment assessment. PRO and physician-reported toxicities comparing IMPT and IMRT were analyzed using the Wilcoxan Rank Sum Test.

Of 126 patients, 48 patients met inclusion criteria. 98% had HPV/p16-positive cancers of the tonsil or base of tongue. 48% were treated with adjuvant radiotherapy, while 52% were treated with definitive-intent radiotherapy. 56% received IMRT while 44% received IMPT.

At the end of RT, patients treated with IMPT reported nonsignificant smaller decrements in dry mouth (p=0.12), sense of smell/taste (p=0.11), and feeling ill (p=0.28). At further follow-up, patients treated with IMPT were using less pain meds and have less swallowing dysfunction, dry mouth, problems with opening mouth, and troubles with social eating.

Physician-reported toxicities showed less severe nausea, oral pain, mucositis, and sore throat with the use of IMPT. At further follow-up, physicians reported less dysphagia, pharyngeal edema, mucositis, sore throat, and oral pain in the IMPT cohort.

For older patients, IMPT demonstrated trends for improvement in multiple acute head and neck symptom domains from both a patient and physician perspective.


DAHANCA 35 - proton versus photon radiotherapy for pharynx and larynx cancer: A randomized trial using a model based enriched population

J. Friborg1,2, K. Jensen2, C.R. Hansen3, E. Andersen4, M. Andersen5, J.G. Eriksen6,7, J. Johansen8, J. Overgaard6, B. Smulders1, C. Grau2,7

1University Hospital of Copenhagen- Rigshospitalet, Oncology, Copenhagen, Denmark, 2Aarhus University Hospital, Danish Center of Particle Therapy, Aarhus, Denmark, 3Odense University Hospital, Laboratory of Radiation Physics, Odense, Denmark, 4Herlev University Hospital, Oncology, Herlev, Denmark, 5Aalborg University Hospital, Oncology, Aalborg, Denmark, 6Aarhus University Hospital, Experimental Clinical Oncology, Aarhus, Denmark, 7Aarhus University Hospital, Oncology, Aarhus, Denmark, 8Odense University Hospital, Oncology, Odense, Denmark

Background: Head and neck cancer patients suffer from serious side effects during and after radiotherapy - side effects that may be reduced with proton therapy. Models, developed in photon radiotherapy, describe the correlation between dose, volume and risk of side effects. DAHANCA, the Danish Head and Neck Cancer Group, has agreed upon that uncertainties concerning dose delivery, RBE and patient selection, justifies a randomization of patients.

Materials and Method: A comparative photon and proton dose plan will be made for all pharynx and larynx cancer patients, except patients with cancer of the nasopharynx and early glottic cancer. If the dose distribution of the proton plan indicates a clinically relevant reduced risk of observer-assessed dysphagia and/ or patients reported xerostomia, using the presently available best models, the patient is offered randomization to either proton or photon radiotherapy (2:1). Objective assessment of swallowing and salivary flow, acute and late toxicity, quality of life, socioeconomic endpoints and locoregional control are other important secondary endpoints.

Results: Inclusion for a feasibility trial is expected to begin in early 2019, and the randomized trial to begin during second half of 2019

Conclusion: National consensus has been reached to perform a complex randomized study with high demands for the decentralized abilities to create comparative dose plans and to refer patients to a national proton center. If the study reaches its goals, groundbreaking evidence will be created to guide the selection of patients for the optimal therapy in the future.


Pencil beam scanning proton radiotherapy in the treatment of nasopharyngeal cancer

J. Kubes1, K. Dědečková1, P. Vítek1, B. Ondrová1, S. Sláviková1, S. Zapletalová1, R. Zapletal1, V. Vondráček1, E. Rotnáglová1, S. Vinakurau1

1PTC Prague, Proton therapy dept., Prague, Czechia

Introduction: Patients with nasopharyngeal cancer are candidates for proton radiotherapy due to large and comprehensive target volumes and necessity of sparing healthy tissues.

Material and methods: Between Jan 2013 to Jun 2018 we treated 40 patients with nasopharyngeal cancer (NPC) with IMPT (proton radiotherapy with modulated intensity). Median of age was 47 years, majority of pts. had locally advanced tumors (stage 2 – 8 pts. (20%); stage 3 – 18 pts. (45%); stage 4A – 10 pts. (25%); stage 4B – 4 pts. (10%). Median of total dose was 74 GyE (70-78 GyE) in 37 fractions (35–39). Bilateral neck irradiation was used in all cases. Concomitant chemotherapy was applied in 34 pts. (85%). Median follow up time is 24 months.

Results: Two-years OS, DFS and LC are 80%, 75% and 84%, respectively. Acute toxicity was generally mild despite large target volumes and application of concurrent chemotherapy, with skin toxicity and dysphagia as most frequent acute side effects. PEG was necessary in 4 pts. (10%). Serious late toxicity (G >3, RTOG) was observed in 1 pt. (2,5%) (dysphagia in patient with pre-existing disease of collagenous tissue).

Conclusion: IMPT for nasopharyngeal cancer patients is feasible with mild acute toxicity. Treatment outcome is promising despite the high percentage of very advanced disease in this group.

Acknowledgement: INAFYM CZ.02.1.01/0.0/0.0/16_019/0000766


Evaluation of robustness of posterior-beam-weighted proton treatment planning for oropharyngeal cancer

S. Park1, J. Kwanghyun1, L. Woojin1, O. Dongryul1, A. Yong Chan1

1Samsung Medical Center- Sungkyunkwan University School of Medicine, Department of Radiation Oncology, Seoul, Korea Republic of

Patients undergoing concurrent chemoradiation therapy (CCRT) for oropharyngeal cancer (OPC) frequently experience tumor regression or weight loss during treatment, which can result in dose delivery degradation such as critical increase on dose to organ-at-risk (OAR) and decrease on dose to target volume. This may require the patient repeat CT simulation to assess the dose change, and then estimate the necessity of adaptive re-planning. When it comes to making decision whether re-planning is required, the robustness of treatment plan against these anatomical change [PS1] must be considered, because it mitigates risks of dosimetric change on target volume as far as robustness ensures, eventually reducing labor-intensive efforts for re-planning. In this study, we present proton treatment planning of OPC which maximize robustness by varying beam weighting in the same beam configuration, observing dosimetric change on OAR we concern. Basically, two beams were used for OPC proton planning which are anterior-oblique (AO) beam and posterior-anterior (PA) beam, and three plans were made varying beam weighting ratio, AO/PA from 1, 2 to 3. Robustness of each plan was evaluated using four synthetic CT in which weight loss is simulated as contracting body contour partially by 2.5, 5, 7.5 and 10 mm. Dose change on OARs such as parotid gland, skin, brainstem and spinal cord were also analyzed. As a result, as weighting ratio increases, dosimetric change on target volume showed less and decrease of average dose decrease on parotid gland was shown, whereas dose on brainstem and spinal cord were increased.


Dosimetric comparison of adjuvant pencil beam scanning protons and intensity modulated radiation therapy following transoral robotic surgery for oropharyngeal cancers

N. Paudel1, S. Schmidt2, M. Ruckman1, S. Gans2, M. Stauffer2, I. Helenowski3, U. Patel4, S. Samant4, M. Gentile1

1Northwestern Memorial Hospital, Radiation Oncology, Chicago, IL, USA, 2Northwestern Medicine Chicago Proton Center, Radiation Oncology, Warrenville, IL, USA, 3Feinberg School of Medicine, Preventative Medicine, Chicago, IL, USA, 4Northwestern Memorial Hospital, Otolaryngology - Head and Neck Surgery, Chicago, IL, USA

Purpose: Post-transoral robotic surgery (TORS) patients have increased swallowing difficulties with adjuvant therapies. For HPV+ oropharyngeal cancer (OPC) patients receiving adjuvant radiotherapy following TORS, pencil beam scanning (PBS) was compared to IMRT for target coverage and dose to organs at risk (OAR).

Methods: Eight consecutive patients were included. Contours were completed by one radiation oncologist. Plans achieved D95 and D99 to the CTV for proton with robustness evaluation for position and range and PTV for IMRT, respectively, while meeting institutional OAR constraints. Prescribed doses included: 60GyRBE (primary site), 54GyRBE, 60GyRBE and 66GyRBE (low-, intermediate- and high-risk disease to bilateral neck). Proton plans utilized 3-4 beams and multi-field optimization. Statistical analysis was performed using the paired-t test.

Results: Compared to IMRT, PBS plans resulted in statistically significant improved D95 (p=0.001) for intermediate risk CTV, lower mean dose to mean total constrictors (49.6Gy vs 36.0GyRBE; p=0.008), mean total larynx (42.0Gy vs 25.0GyRBE; p=0.008), mean oral cavity (33.6Gy vs 19.5GyRBE; p=0.0002), mean ipsilateral parotid (45.6Gy vs 33.7GyRBE; p=0.008), mean contralateral parotid (27.2Gy vs 20.0GyRBE; p=0.008), mean ipsilateral submandibular gland (64.3Gy vs 57.8GyRBE; p=0.03) and maximum spinal cord (42.5Gy vs 32.3GyRBE; p=0.02). There were no statistically significant differences between groups for maximum brainstem, mandible, V45 esophagus or mean contralateral submandibular gland.

Conclusions: There was significant dose reduction to several OARs with PBS vs. IMRT, especially for swallowing structures. Correlating reduction in doses to functional outcomes and cost-effectiveness may be helpful in guiding clinicians to the choice of radiation modality in the post-TORS setting.


Re-irradiation for recurrent scalp angiosarcoma: Dosimetric advantage of proton therapy over VMAT and electron therapy

R. Pidikiti1, M. Kharouta1, N. Damico1, D. Dobbins1, F. Jesseph1, M. Smith1, D. Mansur1, M. Machtay1, M. Yao1, A. Bhatt1

1University Hospitals/Seidman Cancer Center at Case Western Reserve University, Radiation Oncology, Cleveland, OH, USA

Background: Re-irradiation in the scalp area can be challenging given proximity to the organs at risk (OAR) like the eye and underlying brain. Our aim is to evaluate the dosimetric differences of volumetric modulated arc therapy (VMAT) and electron beam therapy (EBT) in comparison to 3-D proton beam therapy (PBT).

Methods: We evaluate a case of recurrent angiosarcoma of left temporal scalp status post prior tomotherapy overlapping treatments to 60 Gy in 30 fractions. VMAT, EBT and PBT plans were generated using Pinnacle. Both VMAT and EBT plans used a skin bolus versus no bolus used for the proton plan. Doses to the OAR's including cochlea, eyes, lens, lacrimal glands, optic nerves, optic chiasm, pituitary gland and underlying brain were compared.

Results: Re-irradiation treatment dose was 60 GyRBE. Representative comparison of the plan images is shown (Figure 1). Target volume coverage was comparable in all plans. Compared to VMAT and EBT, PBT plan showed significant reductions in mean and max doses to all OAR's (Table 1). Without the use of protons several OARs would have exceeded dose tolerance utilizing VMAT or electrons. Dose reduction of up to 100% was achieved for central and contralateral OAR's.

Conclusions: PBT as compared to VMAT and EBT resulted in meaningful dose reductions to all OAR's, while maintaining excellent target coverage. PBT shows a significant advantage in treating superficially located skin cancers like angiosarcoma without need for a bolus. PBT could be considered in the upfront treatment and certainly in the re-irradiation setting.


Acute toxicity profile in head and neck cancer patients treated with re-irradiation using proton therapy versus intensity modulated radiotherapy

M. Shuja1, D.M. Routman1, R.L. Foote1, Y.I. Garces1, M.A. Neben-Wittich1, S.H. Patel2, L.A. McGee2, W.S. Harmsen3, D.J. Ma1

1Mayo Clinic, Radiation Oncology Department, Rochester, MN, USA, 2Mayo Clinic, Radiation Oncology Department, Phoenix, AZ, USA, 3Mayo Clinic, Biomedical Statistics and Informatics Department, Rochester, MN, USA

Objective: Proton therapy (IMPT) may represent a superior option compared to photon therapy (IMRT) for preserving the balance between treatment-related toxicities and local control for curative head-and-neck re-irradiation (re-RT).

Materials & Methods: We conducted a retrospective analysis of prospectively collected toxicity data for head-and-neck cancer (HNC) patients treated with re-RT using IMPT and IMRT. All patients had at least one prior curative radiation course to the head-and-neck region. Acute toxicity within 3-months of re-RT was recorded using CTCAE version 4.3. Statistical analysis was performed using Fisher Exact and Wilcoxon rank sum tests.

Results: Our cohort included 31 HNC patients treated with re-RT between April 2013 and December 2018 using IMPT (n=14) and IMRT (n=17). Median follow-up was 11 months. 77% (n=24) received definitive intent re-RT, while 23% (n=7) received adjuvant re-RT. Median re-RT dose was 66Gy whereas median total dose was 130Gy. IMPT used conventional fractionation and stereotactic-body-radiotherapy (SBRT) in 7 patients each (50%). IMRT used hyperfractionation in 76% (n=13) and conventional in 18% (n=3) and one SBRT. IMPT had lower rate of grade-3 acute toxicity for any given outcome when compared to IMRT (36% vs 71%, p=0.05), this effect was also seen in conventional IMPT compared to IMRT hyperfractionation (43% vs 69%), although statistically not significant (p=0.25). Toxicities assessed included dysphagia (7.1% vs 41.2%, p=0.03), mucositis (14.3% vs 35.3%, p=0.01), and dermatitis (14.3% vs 29.4%, p=0.02).

Conclusions: IMPT reduced rates of grade ≥3 toxicity in HNC re-irradiation compared to IMRT, despite differences in fractionation schedules. These encouraging results warrant further exploration through larger prospective studies.


18F-fluoromisonidazole (18F-FMISO) PET guided dose escalation with proton therapy in nasopharyngeal carcinoma (NPC): A feasibility and planning study

K. Sommat1, A.K.T. Tong2, J. Hu1, A.L.K. Ong1, F. Wang1, S.Y. Sin1, T.S. Wee1, W.K. Tan1, K.W. Fong1, Y.L. Soong1

1National Cancer Center Singapore, Radiation Oncology, Singapore, Singapore, 2Singapore General Hospital, Nuclear Medicine, Singapore, Singapore

Background: Tumor hypoxia is associated with resistance to radiation and increased rate of local recurrence. Selective dose escalation to hypoxic areas within tumor improve tumor control with acceptable side effects. The purpose of this study was to evaluate from a planning point of view the feasibility of dose painting with proton therapy to hypoxic area identified on 18F-FMISO PET-CT in NPC.

Methods: Nine patients participated in this planning study. Two proton plans were generated for each patient. The initial phase was planned with single-field uniform dose (SFUD) optimization using 2 fields to 10Gy in 2fractions to hypoxic volume identified on 18F-FMISO PET. The second phase was planned with intensity modulated proton therapy (IMPT) with robust optimization to deliver 70Gy to gross tumor volume with simultaneous integrated boost to a dose of 60Gy and 54Gy in 33fractions to high risk clinical target volume (CTV) and low risk CTV respectively. A plan sum was generated for assessment.

Results: Eight patients had identifiable hypoxic volumes on pre-treatment 18F-FMISO PET. The average hypoxic volume was 1.92ml(range:0.97-4.19ml). All plans met predetermined target coverage. The average D95 of hypoxic volume was 80.7Gy (SD:0.23Gy). The average Dmean of right and left parotid glands, brainstem, and chiasm were 22.2Gy, 26.2Gy, 49.3Gy and 16.80Gy respectively. The D1cc of temporal lobes of less than 75Gy was achievable in all but one patient.

Conclusion: Hypoxia-targeted dose painting is feasible with proton therapy without substantial dose increase to normal tissues above tolerance. Clinical trials are warranted to determine the clinical outcomes.


Clinical risk of carcinogenesis from passively scattered proton beams

N. Wallace1, S. Fredericks2, T. Fitzgerald3, F. Vernimmen1

1Cork University Hospital, Radiotherapy Department, Cork, Ireland, 2iThemba LABS, Radiotherapy, Cape Town, South Africa, 3University College Cork, Department of Statistics, Cork, Ireland

Background: Neutron contamination from high Z materials in a passively scattered beam has been cause for concern regarding carcinogenesis because neutrons are quite potent in this regard. Based on a combination of neutron dose measurements and theoretical calculations this risk has been shown to be as low or even lower than for photon irradiation techniques. However, to evaluate the true risk to patients, long term clinical outcomes need to be analyzed.

Methods: We studied a cohort of 322 patients, the vast majority treated for benign conditions, for the occurrence of in field and out of field secondary malignancies (SMs). Of the 322 patients, 164 were female and 158 were male. Ages ranged from 2–85 years, with a median of 40 years. 13% were <20 years, 27% were <30 years, and 69% were <50 years of age at the time of treatment. Their follow up ranged from 25 to 276 months, with a median of 150 months. The 41 patients under the age of 20 had a median follow-up of 15 years.

Results: A variety of 7 out of field SMs developed during the follow-up period, in keeping with observed rates in the general population based on the national cancer statistics. 8 patients developed intracranial meningiomas, but no in-field secondary malignancies were seen.

Conclusions: For out of field SM's no increased risk of developing a malignancy was observed. No SMs were observed in children and young adults.

Clinics: Eye / Breast / Pelvis Poster Discussion Sessions, PTC58-0091

Microdosimetric study and RBE measurement at CATANA proton therapy facility for the treatment of ocular melanoma

G. Petringa1, P. Cirrone1, S. Agosteo2, A. Attili3, F.P. Cammarata4, G. Cuttone1, V. Conte5, C. La Tessa6, L. Manti7, A. Rosenfeld8, P.A. Lojacono1

1Istituto Nazionale di Fisica Nucleare INFN, Laboratori Nazionali del Sud LNS, Catania, Italy, 2Politecnico di Milano, Dipartimento di Energia, Milano, Italy, 3Istituto Nazionale di Fisica Nucleare, Sezione Roma 3, Roma, Italy, 4National Research Council, Institute of Molecular Bio-imaging and Physiology, Cefalù, Italy, 5Istituto Nazionale di Fisica Nucleare INFN, Laboratori Nazionali di Legnaro, Legnaro, Italy, 6Istituto Nazionale di Fisica Nucleare, Trento Institute for Fundamental and Applied Physics, Trento, Italy, 7Università degli Studi Federico II di Napoli, Dipartimento di Fisica, Napoli, Italy, 8University of Wollongong, Center for Medical Radiation Physics, Wollongong, Australia

CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian proton therapy facility dedicated to the treatment of ocular neoplastic pathologies. Since 2002, it's in operation at the LNS-INFN to date 400 patients have been successfully treated. Nowadays, a slightly increased biological effectiveness is considered in clinical proton treatment planning by assuming a fixed RBE of 1.1 for the whole radiation field. However, data emerging from various studies suggest and highlight how variations in RBE, which are currently neglected, might actually result in deposition of significant doses in healthy organs. Accurate knowledge of the RBE increase in eye proton therapy is of extreme importance as the distal part of the SOBP often involves critical anatomical regions like optic nerve and the macula for which an excess of biological dose could lead to patient's vision loss. A collaboration, between INFN-LNS, CMRP UoW, INFN-NA, IBFM-CNR, INFN-LNL, INFN-MI and INFN-TIFPA was established to perform an experimental measurement of major microdosimetric parameter the dose average lineal energy ydto derive RBE value along a typical SOBP for eye proton therapy. Microdosimetry measurements along the SOBP were carried out using silicon-based detector microdosimeter,mini-TEPC and TEPC followed by application of MKM for RBE10calculation. In this study, melanoma cells (MP38) and normal retina (ARPE19) cells were irradiated in a phantom along the same CATANA 62-MeV SOBP for RBE evaluation. Monte Carlo modeling of the same experimental set up using the Geant4 toolkit has been done. The simulated yd were used as the physical input to MKM for RBE10simulations. RBE derived from three mentioned approaches were compared.


Tumor volume definition for ocular proton therapy through advanced MRI imaging

R. Via1, F. Hennings1, A. Pica1, G. Fattori1, J. Beer1, M. Peroni1, G. Baroni2, A. Lomax1, D.C. Weber1, J. Hrbacek1

1Paul Scherrer Institute, Center for Proton Therapy, Villigen, Switzerland, 2Politecnico di Milano, Department of Electronics- Information and Bioengineering, Milano, Italy

Purpose: Treatment planning for ocular tumors is typically based on a simplified eyeball and tumor (TVEP) model scaled to match with the patient's fundus photography, ultrasound imaging and geometrical references provided by surgically implanted tantalum clips. Here we compare this approach with modelling of the eye and tumor delineation based on MR imaging.

Methods: MRI based volumetric ocular biometry was performed on 31 patients. All relevant ocular structures, such as the eye globe, lens, tumor (TVMR) and clips, were manually segmented, and merged into a MR-based eye model. After alignment based on tantalum clips, this model was geometrically compared to the conventional eye model. In addition, the dosimetric consequences of adopting different models were evaluated by applying treatment plans optimised on TVEP to TVMR and vice versa.

Results: The two models show high geometrical similarity as regards the eye globe with median volume ratios of 0.98 (IQR:0.12) and Dice similarity coefficients (DSC) of 0.92 (IQR: 0.03). In contrast, TVMR was on average half the size of TVEP (volume ratio: 0.50, IQR:0.32) with a DSC of 0.62 (IQR:0.21). Dosimetrically, complete target coverage (V95=100%) was measured in 84% of cases when applying the TVEP plan to the TVMR, with coverage not being achieved for ratios of TVMR/TVEP >0.95. Conversely, for plans optimized on TVMR, only 16% demonstrated acceptable coverage of TVEP.

Conclusions: Although MRI remains the most viable solution to replace clip-based identification of intraocular lesions, further developments on MR sequence and, possibly, the integration of ancillary imaging modalities are required.


A novel deep-learning framework applies to analysis the image characteristics of uveal melanoma tissue in MRI

H.G. Nguyen1,2,3, M. Bach Cuadra2,4, R. Sznitman1, A. Schalenbourg5, J. Hrbacek3, D.C. Weber3, A. Pica3

1ARTORG Center- University of Bern- Switzerland, Ophthalmic Technology Lab, Bern, Switzerland, 2CIBM- University of Lausanne, Medical Image Analysis Laboratory, Lausanne, Switzerland, 3Paul Scherrer Institut, Proton Therapy Center, Villigen, Switzerland, 4Lausanne University Hospital CHUV- Switzerland, Radiology Department, Lausanne, Switzerland, 5Jules Gonin Eye Hospital, Adult Oncology Unit, Lausanne, Switzerland

Purpose: To evaluate an automated segmentation pipeline of uveal melanoma (UM) in magnetic resonance imaging using a novel deep-learning technique.

Material and Method: The dataset is composed of 28 healthy adult eyes and 28 UM patients. MR acquisitions are performed with a 1.5T Siemens scanner with the resolution of 0.5x0.5x0.5mm3 for T1-weighted (T1w) and 0.5x0.5x0.5 or 0.82x0.82x0.8mm3 for T2-weighted (T2w). Our method can be summarized in five major steps (see Fig.1: Image analysis proposed framework). First, the pre-processing input data for noise reduction and intensity normalization. Second, the prior shape information extraction of the sclera and lens. Third, the 2D attention map extraction based on a CNN-base classification. Fourth, the tumor and retinal detachment differentiation based on a second CNN-base architecture (Unet) and Gabor textural separation. Finally, a set of image features will be estimated for each object segmented including first-order statistics, shape and textural features.

Results: We evaluate the accuracy of the tumor segmentation by using the Dice coefficient: 83.4±4.5% for T1W and 82.7±5.1% for T2W. Figure 2a&b (Result of tumor and retinal detachment extraction) shows the example of retinal detachment and tumor differentiation in 1 patient.

Conclusions: Our method allows the quantitative image analysis of UM and retinal detachment for the integration of 3D information into the UM proton therapy treatment.


Fluorescence-based verification of the proton beam's position during the irradiation of intraocular tumors

A. Pflaeger1, A. Weber2, S. Seidel3, R. Stark2, J. Heufelder2

1Technische Hochschule Mittelhessen, Fachbereich LSE, Giessen, Germany, 2Charité - Universitätsmedizin Berlin, BerlinProtonen am HZB, Berlin, Germany, 3Helmholtz-Zentrum Berlin für Materialien und Energie, Protonentherapie, Berlin, Germany

The proton therapy of intraocular tumors is usually performed at a horizontal beam line. The patient is looking at a fixation light to insure the optimal irradiation position for the eye. The eye position is verified prior to irradiation by orthogonal X-ray imaging. During the irradiation the anterior part of the eye is observed by a video camera. For on-line verification of radiation field position and eye movements, a novel method based on proton-induced luminescence in blood vessels of the ocular fundus is being tested.

The proton-induced luminescence is measured in a phantom with a blood vessel structure of a typical ocular fundus, which can be filled with fluorescein (c = 1.0 g / l). Therefore, the phantom is positioned in water at 18 mm water depth and irradiated with a spread out Bragg peak. The proton-induced luminescence is detected with a CCD camera.

The position of the irradiation field can be detected with an accuracy of 0.13 mm for applied doses between 8.4 Gy and 23 Gy. The accuracy depends on the location and number of irradiated vessels. A position change of the model in the order of 0.2 mm during the irradiation was be detected within 4 s.

The proton-induced luminescence on the dye fluorescein allows in vivo verification of the irradiation field and eye movement during proton irradiation. Further experiments with more complex cases and optimized imaging are being conducted to demonstrate a clinical implementation.


The cost-effectiveness of proton therapy hypofractionation for regional nodal irradiation in non-metastatic breast cancer

R. Mailhot Vega1, J. Bradley1, N. Lockney2, S. Macdonald3, X. Liang1, A. Mazal4, N. Mendenhall1, D. Sher5

1University of Florida, Radiation Oncology, Jacksonville, USA, 2University of Florida, Radiation Oncology, Gainesville, USA, 3Harvard Medical School- Massachusetts General Hospital, Radiation Oncology, Boston, USA, 4Quirónsalud, Oncology and Radiotherapy, Madrid, Spain, 5UT Southwestern Medical Center, Radiation Oncology, Dallas, USA

Introduction: Regional nodal irradiation (RNI) for early stage breast cancer (ESBC) patients yields improved clinical outcomes but increases mean heart dose (MHD), which correlates with cardiovascular events. Proton therapy reduces MHD, but its cost may be prohibitive. Hypofractionation (HF) may resolve cost barriers. Cost-effectiveness analyses provide insight into the potential value of proton vs photon HF-RNI and may inform trial design for their comparison.

Materials and Methods: A Markov cohort simulation model was designed to explore the cost-effectiveness of proton vs photon HF-RNI from the payer perspective in 16 fractions for patients with non-metastatic breast cancer (NMBC), assuming similar outcomes to conventional RNI (C-RNI). In the base case, patients age 50 entered the model after RT and could develop local or distant recurrence, coronary heart disease (CHD), or death. Framingham risk calculator informed CHD risk, which was modified by the MHD. Subgroup analyses based on primary laterality, relapse risk, and age were performed. A willingness-to-pay threshold of $100,000/QALY was used.

Results: Proton RNI was not cost-effective in the base case nor in women with right-sided cancers. It was cost-effective ($67,490/QALY) for women with left-sided cancers, particularly in left-ESBC (Stages I-II) ($60,664/QALY). Figure 1 demonstrates the relationship between 20-year breast cancer recurrence risk and cost-acceptability. Left-ESBC was cost-effective from the societal perspective.

Conclusion: HF-RNI is not currently the standard of care but is under active investigation. If HF-RNI proves to yield equivalent outcomes to C-RNI, this analysis suggests HF-RNI with proton therapy would be cost-effective and supports its further investigation.


Proton radiotherapy for left-sided breast cancer in patients with pectus excavatum anatomy

S.S. Korreman1, S. Andreasen2, J.B. Petersen3, B.V. Offersen4

1Aarhus University/Aarhus University Hospital, Dept of Oncology- attn Mette Lange, Aarhus C, Denmark, 2Aarhus University, Dept of Physics and Astronomy, Aarhus C, Denmark, 3Aarhus University Hospital, Dept of Oncology, Århus C, Denmark, 4Aarhus UniversityAarhus University Hospital, Dept of Oncology, Århus C, Denmark

Purpose: For breast cancer patients with challenging anatomy, it can be impossible to cover the entire breast and IMN without exceeding dose limits to the organs at risk (OAR) using photon therapy. Proton therapy may present a solution.

Methods and Materials: Five patients with left-sided breast cancer, and pectus excavatum, were included. Three treatment techniques were compared (Eclipse TPS vs13.7): Standard two-field tangential photons, VMAT with two arcs (separate isocenters), and IMPT 2-3 fields (see figure 1). Plan objective was PTV (breast+IMN) 95-107% (50Gy), dose limits to whole heart (V40Gy<5%, V20Gy<10%), left anterior descending coronary artery (LAD, V20Gy=0%, V10Gy<5%) and lung (V20Gy<25%, mean dose<18Gy).

Results: Target coverage was best and most consistent in proton plans – see figure 2a. Target dose could not be achieved with photons, however for proton plans V90%>99% could be achieved for all patients.

For proton plans, doses to OAR were below limits for all patients. For whole heart, mean[range] V40Gy was 1.2[0;5.6] for protons, 1.2[0.2;3.1] for VMAT and 9.2[0.8;16.7] for tangential plans. The mean[range] V20Gy was 1.7[0.7;2.3], 13.6[8.4;27.4] and 16.4[4.2;28.2] for protons, VMAT and tangential plans. Mean heart dose was 1.6[0.9;3.1]Gy, 11.4[7.5;15.1]Gy and 9.2[3.6;14.4]. Doses to LAD are shown in see figure 2b.

For lung, mean[range] V20Gy was 15.6[14.3;17.7] for protons, 30.9[25.8;39.4] for VMAT and 34.7[24.3.51] for tangential plans. The mean[range] mean lung dose was 7.6[7;9.6]Gy, 17.2[15.6;21]Gy and 17.3[12.3;24.4]Gy.

Conclusion: For patients with left sided breast cancer and pectus excavatum, proton therapy could achieve adequate target coverage without compromising doses to OAR for all patients.


Proton partial breast irradiation preferentially spares the heart and lungs over modern whole breast radiotherapy

K. Gergelis1, K. Jethwa1, T. Whitaker1, S. Shiraishi1, S. Ahmed1, D. Shumway1, E. Yan1, S. Park1, K. Corbin1, R. Mutter1

1Mayo Clinic, Radiation Oncology, Rochester, MN, USA

Purpose: To compare target coverage and normal tissue sparing of state-of-the-art photon whole breast irradiation (WBI) and proton partial breast irradiation (PPBI).

Methods: Consecutive women with node negative breast cancer treated with lumpectomy and adjuvant WBI, without regional nodal irradiation, or PPBI were included. WBI was delivered with 3-dimensional conformal tangential fields, targeting the breast CTV with a 5 mm expansion to PTV to a median dose of 40 Gy in 15 fractions. Left-sided WBI patients were treated in deep-inspiratory breath hold. PPBI was delivered with a median of 2 multi-field optimized beams, targeting the lumpectomy cavity plus 1 cm, to a median dose of 21.9 Gy in 3 daily fractions. Setup uncertainty analyses of +/- 3 mm isocenter shifts in each translational axis and 3% beam range uncertainty were performed to ensure robust target coverage and normal tissue sparing. Dosimetric parameters, collected prospectively, are primarily presented as % prescription and we excluded the boost component of WBI for uniformity of plan comparisons.

Results: 836 women were treated between 2015-2018; 762 received WBI (274 [36%] with boost to the lumpectomy cavity), and 74 with PPBI. Patients treated with PPBI were older and had more favorable breast cancer (Table 1). Patients treated with PPBI had comparable target coverage but significantly lower heart and lung doses (Table 2).

Conclusions: PPBI reduces exposure to the heart and lungs. Follow-up is needed to determine if these dosimetric advantages translate into improved clinical outcomes.


Bone marrow suppression during postoperative radiation for bladder cancer and comparative benefit of proton therapy: Phase-II trial secondary analysis

R. Press1, J. Shelton1, C. Zhang2, Q. Dang1, S. Tian1, T. Shu1, C. Seldon1, A. Jani1, J. Zhou1, M. McDonald1

1Winship Cancer Institute of Emory University, Radiation Oncology, Atlanta, GA, USA, 2Winship Cancer Institute of Emory University, Biostatistics, Atlanta, GA, USA

Introduction: For patients with high-risk bladder cancer (pT3+ or N+), locoregional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase-II trial (NCT01954173) is examining the role of postoperative photon radiotherapy for high-risk patients using volumetric modulated arc therapy (VMAT). Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiotherapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose.

Methods: Eighteen (18) enrolled patients (median age 70) were retrospectively analyzed following pelvic radiation per protocol with 50.4-55.8 Gy in 28-31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multi-field optimization technique (Figure).

Results: There was a decrease in mean nadir values compared to pre-radiation values for white blood cells (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC) (all p<0.001), and platelets (p=0.03). Increased mean PBM dose was associated with nadirs in WBC (Pearson CC 0.593, p=0.015), ANC (CC 0.597, p=0.024) and hemoglobin (CC 0.506, p=0.046), while the PBM V5-V20 was correlated with platelets (Table). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (p<0.001) and had significant reductions in the volume of PBM receiving doses from 5-40 Gy.

Conclusion: Increased mean PBM dose was associated with decreased hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.


Organ sparing potential and intra-fraction robustness of IMPT for cervical cancer

E. Gort1, J.C. Beukema1, M.J. Spijkerman-Bergsma1, S. Both1, J.A. Langendijk1, W.P. Matysiak1, C.L. Brouwer1

1University Medical Center Groningen, Department of Radiation Oncology, Groningen, Netherlands


Chemoradiation (CHRT) for cervical cancer results in severe chronic bowel toxicity and acute hematologic toxicity often causing CHRT discontinuation. IMPT may reduce OAR dose, however inter- and intrafraction variability may affect target coverage. While interfraction variability can be addressed by adaptive replanning strategies, robustness against intrafraction variability should be maintained.

Purpose: To report on the potential of IMPT to reduce OAR dose and to study target coverage robustness of IMPT compared to VMAT versus intrafraction motion.

Materials and Methods: Pre-fraction and post-fraction repeated CTs (reCTs) from 5 cervical cancer patients were available, for whom target volumes included the para-aortic region. Two-field IMPT (2F), four-field IMPT (4F) and two-arc VMAT primary treatment plans were created. Each reCT was contoured and registered to the planCT. Subsequently, all 3 plans were recomputed and target coverage robustness against isocenter shifts and range uncertainty was evaluated on each reCT. Nominal OAR doses and the worst case post-pre intrafraction dose differences delivered to 98% of the GTV and CTV (GTV + uterus + vagina) vs intrafraction bladder volume differences were analyzed.

Results: Mean whole bowel dose was reduced by nearly a half (Figure 1A) and all OAR doses were significantly lower (Table 1) for both IMPT plan types compared to VMAT. IMPT showed similar target coverage robustness as VMAT against all intrafraction bladder volume changes (Figure 1B).

Conclusion: Robustly optimized IMPT treatment plans for cervical cancer patients show equivalent robustness against intra-fraction variability when compared to VMAT treatment plans, but offer significantly better OAR sparing.

Clinics: CNS / Pediatrics / Lung Poster Discussion Sessions, PTC58-0156

An analysis of vertebral body growth on pediatric cancer patients after proton radiotherapy

K. Baba1, H. Numajiri1, K. Murofushi1, Y. Oshiro2, M. Mizumoto1, K. Onishi1, T. Nonaka1, H. Ishikawa1, T. Okumura1, H. Sakurai1

1University of Tsukuba hospital, Radiation Oncology, Tsukuba, Japan, 2Tsukuba Medical Center Hospital, Radiation Oncology, Tsukuba, Japan

Purpose: To predict body growth, we analyzed the relationship between the vertebral body (VB) growth and the irradiation dose of the proton therapy (PT) in children.

Methods: Between 2009 and 2017, 21 pediatric patients who received PT to the VB were selected in this study. These patients included 9 males and 12 females, and had a median age of 4 years (range 2-10). The tumor was as follows; neuroblastoma 11, Wilms' tumor 3, Ewing's sarcoma 2, ependymoma 2, Hairy cell astrocytoma 1, Nasopharyngeal carcinoma 1 and Renal cell sarcoma 1. The VB height was measured with CT or MRI before and about 1 year after PT, and the growth rate (% per year) in each VB height was calculated. The irradiation dose for each VB was evaluated with dose distribution. Measurable non-irradiated VBs were also evaluated as control.

Result: Median observation period was 13.7 month (9.4 – 19.1). 312 vertebral bodies were evaluated (182 were irradiated, 130 were non-irradiated). Of 312, 50 were cervical, 187 were thoracic and 75 were lumber spine, respectively. Median PT dose was 30.6 Gy (RBE) (range 10.8 - 56.8). Analyzing all VBs, negative correlation between the PT dose and the growth rate was significantly observed (p = 0.001). Median growth rates were 8.0% and 3.3% at non-irradiated and irradiated VBs.

Conclusion: Significant correlation between the growth rate of the VB height and PT dose was estimated. Using this approach, we can establish a method to predict the body height in each pediatric cancer patients.


Shape and texture analysis of skull-base chordomas to predict the outcome of pencil beam scanning proton therapy

M. Dominietto1, K. Adam1,2, A. Pica1, F.J. Ahlhelm3, A.J. Lomax1, S. Safai1, D.C. Weber1

1PSI- Paul Scherrer Institute, Center for Proton Therapy, Villigen, Switzerland, 2University of Alabama at Birmingham, Department of Radiation Oncology, Birmingham- Alabama, USA, 3Kantonsspital Baden, Institute of Radiology, Baden, Switzerland

Purpose: Skull-base chordomas (sbC) are rare bone tumors presenting within the clivus or spinal axis, characterized by significant tissue heterogeneity. Their shapes are variable, likely determined by proximity to surrounding anatomic barriers, making them a typical indication for proton therapy (PT). Here we investigate whether shape and/or textural features of the pre-treatment tumor correlate with clinical outcome.

Methods: We retrospectively analyzed 50 sbC patients treated using PBS-PT at our institute. Pre-PT tumor shape and texture (Tab.1) were evaluated on DWI- and T2w-MRI images using in-house developed software and were classified using clustering algorithms (Kmeans) considering both tumor and organs-at-risk (OARs) features, which were cross-correlated with recurrences.

Results: Fig,1 shows two contrasting tumors. (a) is a case with high sphericity and small surface-area (0,86 and 2409mm^2) which did not recur. In contrast the tumor in (b), with values of 0,27 and 8846mm^2 respectively, did recur. Overall, clustering analysis uniquely identified 4 out of 5 recurrences based on these morphological features. However, due to the small number of recurrences, this result is not statistically significant. Other features, such as compactness and signature-mean were significantly correlated (correlation-coeff.>0.85; Fig.1c) but no correlation was observed between textural features and clinical outcome.

Conclusion: Sphericity and surface-area have been found to be potential predictive factors for treatment outcome in sbC. Greater surface values and protrusions (e.g. Fig.1b) could indicate a larger area of contact between tumor and normal-tissue, thus increasing the probability of tumor infiltration. We are currently extending our analysis to a larger patient cohort.


Radiation-induced brain injury in meningioma patients treated with proton or photon therapy

S. Aljabab1, L. Abdul-Jabbar2, J. Song2, Y. D. Tseng3, J. Rockhill3, J. Fink4, L. Chang2, L. M. Halasz3

1Roswell Park Cancer Center, Radiation Medicine, Buffalo, USA, 2University of Ottawa, Radiation Oncology, Ottawa, Canada, 3University of Washington, Radiation Oncology, Seattle, WA, USA, 4University of Washington, Radiology, Seattle, WA, USA

Purpose: It is unclear whether rates of brain injury are different with proton therapy due to uncertainties in end of range effects. This study compares rates of brain injury after proton or photon therapy.

Materials and Methods: We retrospectively reviewed 38 patients treated with proton therapy and 39 treated with photons. Re-irradiation patients were excluded. Radiation induced brain injuries were categorized into white matter lesions (WML) defined as newly detected abnormal T2 signal intensities, or radiation necrosis (RN) defined as newly detected abnormal T2 and T1 post contrast signal intensities. Imaging was reviewed by an experienced neuro-radiologist and radiation oncologist. Toxicity was graded as per CTCAE v4.03.

Results: Median follow-up time was 18 mo for proton and 24 mo for photon therapy. There was no significant difference between the groups for WHO grade, radiation dose, history of diabetes, or history of stroke. The cumulative incidence of WML at 2 years was 38.3% after proton and 45.0% after photons (p=0.60). The cumulative incidence of RN at 2 years was 17.9% after proton and 4.2% after photons (p=0.01). With protons, grade ≥2 was recorded in 7 patients and one patient had a grade 4/5 event. With photons, grade ≥2 was recorded in 3 patients and one patient had a G4/5 event.

Conclusion: Patients treated with radiation have high rates of developing T2 signal intensity abnormalities. However, in our series, patients were more likely to develop parenchymal T1 post contrast abnormalities after proton therapy. Additional studies are required to confirm these findings.


Active spot-scanning proton therapy for intracranial meningiomas: CNAO experience

E. Dippolito1, A. Iannalfi2, B. Vischioni2, M.R. Fiore2, S. Ronchi2, M. Bonora2, V. Vitolo2, A. Barcellini2, F. Valvo2, R. Orecchia2

1National Center of Oncological Hadrontherapy CNAO, Radiotherapy Unit, Pavia, Italy, 2National Center of Oncological Hadrontherapy CNAO, Radiation therapy Unit, Pavia, Italy

Objective: Proton therapy (PT) is an alternative therapeutic option for unresectable meningiomas, mostly located in the skull-base, and a complementary treatment for complex and irregular tumors located in close proximity of critical organs at risk (OAR) as optic-pathways and brainstem where only subtotal or partial resection is possible. Aim of the study was to evaluate treatment results and toxicity in patients (pts) with meningiomas treated with active spot-scanning PT

Methods: 79 pts with intracranial meningioma (histologically proven 50/79) were treated with PT between October 2012 to December 2017. Pts, tumor and treatment characteristics were summarized in Tab1. 59 pts had skull-base lesions. 44 pts were treated as primary treatment (exclusively PT=32 pts, postoperative PT=12 pts), 35 pts were treated for recurrence after surgery. 29 pts had radiological diagnosis (28/29 skull-base lesions) and in all these cases 68Ga-DOTATOC-PET was performed before treatment. The total dose was 55.8 Gy (RBE). GTV ranged from 2.3-205.71 cm3. Toxicity was assessed according to CTCAE- V4.03 scale.

Results: median follow-up was 17 months. No high-grade (grade 3-4) treatment-related toxicity was observed. Local control was 99%. Only one patient, affected by atypical meningioma, had local recurrence 22 months after the end of the treatment. Two pts with atypical and anaplastic meningioma respectively had “out-of-field” recurrence 20 and 8 months after the end of the treatment.

Conclusions: PT is a safe and effective treatment for pts with intracranial meningiomas, and it allows to deliver high local doses even in complex anatomy (as skull-base lesions) while sparing critical OARs


Proton beam therapy for meningioma: Treatment outcome and toxicity

F. Guntrum1, T. Steinmeier2, S. Nagaraja1, D. Jazmati1, D. Geismar3, B. Timmermann3, S. Plaude2

1Department of Particle Therapy- University Hospital Essen, West German Proton Therapy Center WPE- West German Cancer Center WTZ, Essen, Germany, 2West German Proton Therapy Center Essen WPE, West German Cancer Center WTZ- University Hospital Essen, Essen, Germany, 3Department of Particle Therapy- University Hospital Essen, West German Proton Therapy Center WPE- West German Cancer Center WTZ- German Cancer Consortium DKTK, Essen, Germany

Purpose: Proton beam therapy (PT) is of increasing interest especially in tumors in close proximity of critical structures like skull base meningioma. Treatment outcome and toxicity data collected in a prospective registry of a single institution are presented.

Methods: Between July 2013 and May 2018, 55 adult patients with meningioma with a median age of 55.7 y (20.1-79.6 y) were treated and were prospectively enrolled in the in-house registry ProReg. The cohort consisted of 15 male and 40 female patients. Histopathology included WHO °I (36, 65.5%) and WHO °II (8, 14.5%). Eleven patients (20%) received no biopsy. Twenty-two (40%) patients received definitive PT. Adjuvant PT was administered after gross total resection and subtotal resection in 8 (14.5%) and 25 (45.5%), respectively. The median total dose of PT was 54Gy (54-60Gy) applied in 27 (27–33) fractions.

Results: The median follow-up time from the primary diagnose was 3 years (0.4 – 26.1 y) and after the end of PT 1 year (0-4.5 y). Local disease control was achieved in 52 patients (94.5%). Local recurrence occurred in 1 patient and 2 patients had local progress after treatment. All patients were alive at last follow-up. PT was well-tolerated. No new higher-grade (CTCAE ≥°3) acute toxicity occurred. Long-term follow-up after PT showed 1 new CTCAE °3 toxicity as increasing vision deficit due to tumor progression.

Conclusion: Current data support good early tumor control and feasibility of PT in meningioma. However, further follow-up data is required to assess long-term outcome.


Proton therapy for craniospinal radiochemotherapy (chemo-CSI) reduces myelotoxicity and improves chemotherapy completion in adult medulloblastoma (aMB)

C. Lynch1, K. Petras1, W. Hartsell2, J. Chang3, S. Grimm4, R. Lukas4, P. Kumthekar4, R. Merrell5, J. Kalapurakal1, V. Gondi1, J. Gross1

1Northwestern University Feinberg School of Medicine, Radiation Oncology, Chicago, IL, USA, 2Northwestern Medicine Chicago Proton Center, Radiation Oncology, Chicago, IL, USA, 3Vanderbilt University Medical Center, Radiation Oncology, Nashville, TN, USA, 4Northwestern University Feinberg School of Medicine, Neurology, Chicago, IL, USA, 5Northshore University Health System, Neurology, Chicago, IL, USA

Purpose: Combined radiochemotherapy for aMB improves survival versus radiation alone but is highly toxic. Proton therapy for chemo-CSI spares vertebral marrow, potentially reducing myelotoxicity and improving rates of chemotherapy completion. This analysis tracks myelotoxicity and chemotherapy completion rates in aMB patients treated with proton chemo-CSI, comparing them to NOA-07 trial results for photon chemo-CSI.

Methods: Patients age≥15 were included if they received vertebrae-sparing proton chemo-CSI for newly-diagnosed aMB and were planned to receive concomitant-phase vincristine during radiotherapy followed by ≥4 cycles of adjuvant chemotherapy. Craniospinal axis was treated to 23.4 or 36 CGE with subsequent boost to 54-55.8 CGE. Myelotoxicity and chemotherapy completion were evaluated using NOA-07 criteria. Correlations with toxicities were conducted using chi-square analysis; survival estimated using Kaplan-Meier method.

Results: Twenty-four (24) patients at a single institution met inclusion criteria. Median follow-up was 2.4 years. Median age was 28 (range: 18-58), 46% were female, 54% average-risk, and 50% received 23.4 CGE CSI. 2-year PFS and OS were 88% and 100%, respectively. Of 21 patients with available hematologic data: 95% received cisplatin, 76% vincristine, 67% CCNU, and 62% cyclophosphamide. 86% and 80% completed ≥4 and ≥6 cycles of adjuvant chemotherapy, respectively, versus 70% and 63% in NOA-07. Adjuvant-phase cyclophosphamide use correlated with grade≥3 leukopenia (p<0.01) and neutropenia (p=0.01). Table 1 displays myelotoxicity results.

Conclusions: Proton chemo-CSI for aMB increases rates of adjuvant chemotherapy completion, reduces rates of concomitant-phase leukopenia and, excluding patients receiving cyclophosphamide, lowers rates of adjuvant-phase myelotoxicity compared to photon chemo-CSI control (NOA-07, which omitted cyclophosphamide).


A Proton Collaborative Group(PCG) Phase I Study of hypofractionated proton therapy for stage II-III non-small cell lung cancer

B. Hoppe1, C. Simone2, R.C. Nichols1, D. Pham3, P. Mohindra4, N. Mohammed5, B. Chon6, C. Morris1, Z. Li1, S. Flampouri7

1University of Florida Health Proton Therapy Institute, Radiation Oncology, Jacksonville, FL, USA, 2NY Proton Therapy Institute, Radiation Oncology, New York, NY, USA, 3University of Florida College of Medicine, Medical Oncology, Jacksonville, FL, USA, 4University of Maryland, Radiation Oncology, College Park, MD, USA, 5Northwestern Medicine, Radiation Oncology, Chicago, IL, USA, 6Procure New Jersey, Radiation Oncology, Somerset, NJ, USA, 7Emory Proton Therapy Institute, Radiation Oncology, Atlanta, GA, USA

Background: We investigated whether proton therapy would allow for safe dose intensification with concurrent chemotherapy for patients with stage II/III non-small cell lung cancer (NSCLC).

Methods: Eighteen patients from four different Proton Collaborative Group institutions were enrolled and treated on an IRB-approved prospective phase I study. Patients received concurrent chemotherapy with hypofractionated proton therapy to a planned total dose of 60 Gy(RBE), but with increasing dose per fraction in a 5x5 step-wise fashion. Arm 1 delivered 2.5 Gy/fraction (n=5); arm 2 delivered 3 Gy/fraction (n=5); arm 3 delivered 3.53 Gy/fraction (n=7); and arm 4 delivered 4 Gy/fraction (n=1). Dose arms were considered safe provided 0 of 5 or 1 of 7 patients developed a radiation-related serious adverse events (SAEs) within 90 days of starting treatment. Patients received consolidative chemotherapy or immunotherapy after completing concurrent therapy per institutional policies.

Results: No radiation-related SAEs occurred within the first 90 days on arm 1 or 2. One patient developed an SAE on arm 3; however, no further SAEs occurred on arm 3 after 7 patients were enrolled. One patient received treatment on arm 4 and did not develop an SAE.

Conclusions: Hypofractionated proton therapy with concurrent chemotherapy to a dose of 60 Gy(RBE) in 2.5-3.53 Gy/fraction is well-tolerated. A phase II study of hypofractionated proton therapy with concurrent chemotherapy for patients with stage II/III NSCLC is warranted.


Patient engagement in the design of a randomised trial of proton beam radiotherapy versus photon radiotherapy for good prognosis glioma

J.R. Powell1, L. Murray2, N. Burnet3,4, S. Fernandez5, Z. Lingard3, L. McParland6, D. O'Hara7, G. Whitfield3,4, S.C. Short2

1Velindre University NHS Trust, Clinical Oncology, Cardiff, United Kingdom, 2University of Leeds, St James's Hospital and Leeds Institute of Medical Research, Leeds, United Kingdom, 3University of Manchester- Cancer Research Center, Division of Cancer Sciences, Manchester, United Kingdom, 4The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom, 5Leeds Teaching Hospitals NHS Trust, Clinical Oncology, Leeds, United Kingdom, 6University of Leeds, Clinical Trials Research Unit, Leeds, United Kingdom, 7Leeds Teaching Hospitals NHS Trust, Clinical and Health Psychology, Leeds, United Kingdom

Introduction: UK Neuro-Oncologists and multidisciplinary colleagues are developing one of the first randomised clinical trials of proton beam radiotherapy (PBT) to compare quality of life (QOL), cognitive function and other late effects in adults with good prognosis glioma following either PBT or photon radiotherapy. The feasibility of running randomised studies with PBT is an important consideration, particularly in respect of participants' views of a randomised design requiring treatment at national centers. We sought patient and carer engagement on our proposals to ensure we incorporate their views.

Methods: To explore these issues, we invited patients who had previously completed radiotherapy for oligodendroglioma and their carers to attend a focus group in Manchester in November 2018. Fifteen participants attended. We sought views on our trial proposal through small group discussions centerd around 5 questions, led and facilitated by neuro-oncologists, a research radiographer,neuro-psychologist and statistician.

Results: Participants strongly endorsed the trial proposal and positively highlighted the opportunity to access PBT within a clinical trial and the group recognised and supported the need for randomisation and stated this should be 1:1. Patients disliked some traditional terminology such as ‘trial' and ‘neurocognitive tests' and preferred ‘research study' and ‘neurocognitive assessments'. Patient and carers expressed the need for careful consideration of issues around travel and accommodation during PBT away from home. Interestingly, participants considered that standard QOL questionnaires fail to address some important areas reflecting daily wellbeing.

Conclusion: We acknowledge and will now incorporate these important patient and carer observations to strengthen our study and add validity to the key study endpoints.


Preliminary results of pencil beam scanning proton and carbon ion therapy for skull base and cervical spine chordoma and chondrosarcoma

X. Guan1, J. Gao1, J. Hu1, W. Hu1, J. Yang1, X. Xing2, C. Hu2, L. Kong2, J. Lu1

1Shanghai Proton and Heavy Ion Center, Department of Radiation Oncology, Shanghai, China, 2Shanghai Proton and Heavy Ion Center- Fudan University Cancer Hospital, Department of Radiation Oncology, Shanghai, China

Purpose: to evaluate the short-term tumor control and toxicity of skull base and cervical spine chordoma and chondrosarcoma in patients treated with pencil beam scanning proton and heavy ion therapy.

Methods: Between May 2014 and December 2017, a total of 84 patients have been treated with proton and/or carbon ion RT in shanghai proton and heavy ion center. There was 47 male and 37 female patients. The median age was 37 years (range, 14-70 years). 41(48.8%) patients were treated for primary tumors, whereas 43(51.2%) had recurrent tumors after surgery and/or radiotherapy. Thirteen (15.5%) of all the patients received radiotherapy previously. The median gross tumor volume was 36.5cc (range: 1.6-232cc).

Results: Eight patients received proton therapy, 28 patients received combined proton and carbon ion therapy, 48 patients received carbon ion therapy. The median follow-up period was 24 months (range, 3-91 months). For the entire cohort, the 2-year local control, progression free and overall survival rate was 88.2%, 78.5%, and 86.3% respectively. On multivariate analyses, more than 50cc GTV volume (0.033) was the significant factor for predicting PFS, while re-irradiation (p=0.003) was the only significant factor for predicting OS. The acute toxicity was mild with on grade 3-4 effects. Late toxicities of unilateral temporal lobe changes in 2 patients.

Conclusions: The short-term outcome of particle therapy for chordoma and chondrosarcoma was favorable. Larger tumor volume and re-irradiation was related to inferior survival. Further follow-up is needed for long-term efficacy and safety.


Scanning beam proton therapy versus photon IMRT for stage III lung cancer: Comparison of dosimetry, toxicity and outcomes

Z. Zou1, S. Bowen2, H. Thomas3, B.K. Sasidharan4, R. Rengan3, J. Zeng3

1Union Hospital- Tongji Medical College- Huazhong University of Science and Technology, Cancer Center, Wuhan, China, 2University of Washington Medical Center, Radiation Oncology & Radiology, Seattle, WA, USA, 3University of Washington Medical Center, Radiation Oncology, Seattle, WA, USA, 4Christian Medical College, Radiation Oncology, Vellore, India

Purpose: There is limited clinical data on scanning-beam proton therapy (SPT) in treating locally-advanced lung cancer, as most published literature is with passive-scatter technology. There is increasing interest in whether the dosimetric advantages of SPT compared with photon therapy can translate into superior clinical outcomes. We present our experience of SPT and photon intensity-modulated radiation therapy (IMRT) with real-life dosimetry, and outcomes in patients with stage III non-small cell lung cancer (NSCLC).

Methods: Patients with stage III NSCLC treated at our center between 2013-May 2018 were identified in compliance with an IRB-approved study (64 patients=34 SPT +30 IMRT). Most proton patients were treated with pencil-beam-scanning (28/34), 6/34 with uniform-scanning. Fisher's exact test, Chi-square test, and Mann-Whitney test were used to compare groups. All tests were two-sided.

Results: Patient characteristics are in Table 1. Mean dose to lung, heart, and esophagus were lower in the SPT group, with most benefit in the low dose region (Table 2). Esophagitis and dermatitis grades were not different between the two groups (Table 2). Grade 2+ pneumonitis rate was 21% in the SPT group and 40% in the IMRT group (p=0.1). Overall survival and progression free-survival were not different between SPT and IMRT.

Conclusions: We report our experience with scanning beam proton therapy and photon IMRT in stage III NSCLC, showing lower dose to normal organs (lungs, heart, esophagus) with SPT than IMRT. There is no statistically significant difference in toxicity rates or survival, although there may be a trend towards lower rates of pneumonitis.

General: New Horizons, PTC58-0621

Proton beam diagnostics for ultra-high dose rate irradiations

S. Busold1, J. Heese1

1Varian Medical Systems, Proton Solutions, Troisdorf, Germany

In the context of the novel FLASH radiotherapy mode, irradiations at ultra-high dose rates are increasingly becoming of interest. To ensure controlled and correct dose application in this yet largely unexplored dose application regime, adaptations in beam diagnostics are necessary and several possible options are already published for experimental electron Linacs [1, 2] as well as a proton machine [3]. We present a successfully tested and currently in use solution for our ProBeam spot scanning proton therapy system, which enables small animal irradiations in only a fraction of a second with doses of 25 Gy and higher and a dose reproducibility within <2%. [1] E. Schueler et al., Int J Rad Onc 97, 1, 195-203 (2017). [2] M. Jaccard et al., Medical Physics 45, 2, 863-874 (2017). [3] A. Patriarca et al., Int J Rad Onc 102, 3, 619-626 (2018).


Online beam and range monitoring in a static toroidal gantry delivery configuration

P. Cerello1, L. Bottura2, E. Felcini2, V. Ferrero1, V. Monaco3, F. Pennazio1, G. de Rijk2

1INFN, Sezione di Torino, Turin, Italy, 2CERN, Technology Department, Geneva, Switzerland, 3University of Torino, Department of Physics, Turin, Italy

GaToroid is a novel fixed toroidal gantry, based on superconducting magnets, able to deliver the dose at discrete number of angles without rotation of the magnets or the patient. In order to become a feasible option for particle therapy delivery, it requires the integration of beam and range monitoring functionality.

We propose to implement the beam monitoring through high timing resolution pixelated silicon detectors that will match the beam delivery windows foreseen by the GaToroid design. Moreover, we plan to exploit the azimuthal gaps between the beam entrance windows by installing PET detectors that will provide high–precision online range monitoring.

In terms of performance, the fully integrated delivery and monitoring system would allow:

  • highly flexible and fast beam delivery, with a static gantry much lighter and smaller than the existing ones, subjected to no restrictions on beam timing, beam energy or positioning precision associated to its movement;

  • beam monitoring with single particle counting capability for fast measurement of beam fluence and position;

  • online range monitoring by means of a 3D measurement of the beam-induced activity distribution and of the prompt gamma emission profile, with the goal of an overall range precision of about 1mm obtained within 1 minute of the treatment delivery start.

Preliminary results of the system design simulations and of the expected performance will be presented.


Plan for new multi-modality therapy in Daejeon, Republic of Korea

H. Chang1, C. KyungDon2,3, H. Byunghun1, C. Gyuseong1

1Korea Advanced Institute of Science and Technology, Institute for Information Technology Convergence, Deajeon, Korea Republic of, 2Centro Nazionale di Adroterapia Oncologica, Medical Physics, Pavia, Italy, 3University of Pavia, Department of Physics, Pavia, Italy

Recently South Korea has had two hadron therapy centers under construction: The Korea Institute of Radiological & Medical Sciences in Gijang and Yonsei University Hospital in Seoul. In addition, South Korea already has two proton centers: The National Cancer Center and Samsung Proton Center. However, there is still lack of particle therapy facilities compared to the number of cancer patients. Interest in hadron therapy is increasing, yet all centers are focused on clinical therapy, not intensive research. In general, the number of patients that require treatment with proton therapy is higher than carbon therapy; still, the requirement for both ions are solid. For this reason, the city of Daejeon, located in the center of South Korea, is planning a new multi-modality therapy center associated with the Korea Advanced Institute of Science and Technology. This center is aiming to treat patients with both protons and carbon ions associated with basic research. The Daejeon multi-modality therapy center will not only help covering the lack of proton therapy center but also provide effect of carbon ion treatments. Daejeon's multi-modality therapy center will also invest intensively in research, such as new hadron therapy technology, medical imaging associated and knowledge transfer.


Survey on variations of knowledge and perception amongst radiation oncologists across India regarding proton beam therapy (PBT)

S. Chilukuri1, R. Jalali1, P.K. Panda2

1Apollo Proton Cancer Center, Radiation Oncology, Chennai, India, 2Apollo Proton Cancer Center, Clinical Research, Chennai, India

Background: This survey aims to provide an insight into the variations of knowledge and perception amongst radiation oncologists across India regarding proton beam therapy (PBT).

Methods: Participants of this anonymized online survey included radiation oncologists from all over India. Unique links were electronically mailed from a database populated from professional associations. Descriptive statistical analysis was applied to closed-ended questions, expressed as frequency for categorical variables. Chi-square test and Fisher's exact test was used for comparisons.

Results: Total number of respondents were 253.Seventy percent respondents said 1-10% patients from their current practice were eligible for PBT. Modern PBT significantly different from older proton techniques as believed by 74% respondents. Although 50% respondents believed PBT is suitable for only small sized tumors; chordomas, chondrosarcomas, other skull base tumors (94%) followed by pediatric tumors (90%) were the top indications for PBT. Dose-escalation possibility was believed to be amongst the top PBT benefits by 82% respondents in adults. Limited access (67%), lack of high-quality evidence (61%) for PBT are responsible for slower adoption of PBT across the world, while in India it is lack of awareness amongst the practitioners (46%) and public (30%). Conducting randomized controlled trials (PBT vs photon) for children was deemed ethical by 69% respondents. Need for more awareness about PBT was expressed by 90% respondents.

Conclusion: In view of the wide variation in perception and knowledge amongst the radiation oncologists across India, our survey provides significant information which can act as a suitable benchmark to create awareness regarding PBT.


ELIMED/ELIMAIA: The first Users beamline dedicated to irradiation studies with laser-driven ion beams

P. Cirrone1,2, G. Cuttone1, G. Korn2, G. Larosa1, G. Petringa1, A. Russo1, F. Schillaci2, V. Scuderi1, D. Margarone2, P.A. Lojacono1

1INFN, Laboratori Nazionali del Sud, Catania, Italy, 2ELI, ELI-Beamlines, Prague, Czechia

The main direction proposed by the community in the field of laser-driven ion acceleration is to improve particle beam features in order to demonstrate reliable approaches to be used for multidisciplinary applications.

The mission of the laser-driven ion target area at ELI-Beamlines (Extreme Light Infrastructure) in Czech Republic, called ELI Multidisciplinary Applications of laser-Ion Acceleration (ELIMAIA), is to provide stable, fully characterized and tuneable beams of particles accelerated by Petawatt-class lasers and to offer them to the user community for multidisciplinary applications. The focusing, selecting, measuring and irradiating parts of ELIMAIA, constitutes the so-called ELIMED (ELI MEDical and multidisciplinary applications) portion.

At ELIMED, very high-dose-rate (not less than 10^5 Gy/min) controlled proton and ion beams, with energy ranging from 5 to 250 MeV, will be transported up to the in-air section where absolute dosimetry will be carried out. A transmission, dual-gap air ionisation chamber will provide the on-line measure of the dose at the irradiation point. The maximum expected error in the final dose released to the sample is expected to be within 5%. ELIMED first irradiation is scheduled for 2020 when the first radiobiological campaign for in-vitro cells irradiation with controlled fast beams is expected.

In this work, the status of the ELIMED/ELIMAIA beamline will be reported along with a complete description of the main dosimetric systems and of the first preliminary calibrations. The expected final beam characteristics, in terms of dose per pulse, dose-rate, beam spot size, directly derived by Monte Carlo simulations, will be reported, as well.


Proton grid therapy: Dosimetric characterization of planar slit collimators

E. Fredén1, E. Almhagen2, Y. Mejaddam1, A. Siegbahn1,3

1Stockholm South General Hospital, Department of Oncology, SE-118 83 Stockholm, Sweden, 2Uppsala University, Medical Radiation Sciences- Department of Immunology- Genetics and Pathology, SE-751 85 Uppsala, Sweden, 3Karolinska Institute, Department of Clinical Science and Education, SE-171 77 Stockholm, Sweden

Introduction: The narrow beams used in proton grid therapy can be produced with collimators. In this study we have carried out a dosimetric characterization of single-slit collimators of different slit widths (SW). We compared experimental results obtained at a pencil-beam scanning beam line with results obtained from Monte Carlo (MC) simulations.

Method: Single-slit brass-alloy collimators (SW = 1, 2, 3 mm) were mounted on the nozzle snout. Transversal dose profiles were measured for monoenergetic 100 MeV beams with the Lynx detector at three depths (z = 4, 24, 76 mm) in a solid water phantom. A beam model of the Skandion Clinic (Uppsala) beam line was implemented in the TOPAS simulation software. Three collimator–phantom distances (CPDs) of 0, 60 and 285 mm were used in the simulations to study the importance of this variable for the dose distributions produced.

Results: The Lynx measured values and the MC simulation results are in close agreement which indicates that the beam model used in the simulations produces realistic results (Figure 1). The CPD influences the measured field size, and the dose distribution produced by collimator scatter to a large extent (Figure 2).

Conclusions: The collimator should be placed as close to the irradiated object as possible to reduce the dose produced in between the narrow beams at the entrance surface. The beam model used in this work can be used for further studies related to multi–slit collimation of proton beams.


New 3D-microdetectors for microdosimetry in proton minibeam

C. Guardiola1, F. Gómez2, J. Prieto-Pena2, C. Fleta3, L. De Marzi4, Y. Prezado5

1Center national de la recherche scientifique CNRS, Imagerie et modélisation en neurobiologie et cancérologie IMNC-CNRS, Orsay Ville, France, 2University of Santiago de Compostela, Dept. Física de Partículas- Atómica- Molecular y Nuclear, Santiago de Compostela, Spain, 3Centro Nacional de Microelectrónica, Micro and nanotechnologies, Barcelona, Spain, 4Institut Curie, Center de Protonthérapie d'Orsay, Orsay Ville, France, 5Center National de la Recherche Scientifique CNRS, Laboratoire d'Imagerie et Modélisation en Neurobiologie et Cancérologie IMNC-CNRS, Orsay Ville, France

The development of new solid-state devices has opened the experimental verification of the hadron therapy beam LET distribution even at nominal fluence rates. This new instrumentation can be used to commission the clinical beams and also to assess the Relative Biological Effectiveness (RBE). Likewise, proton minibeam radiation therapy (pMBRT) is a novel concept that combines the benefits of proton therapy with a remarkable normal tissue preservation when irradiated with submillimetric spatially fractionated beams. This promising technique has already been implemented at a clinical center (Institut Curie-Proton therapy center of Orsay, ICPO) by means of a first prototype of a multi-slit collimator. The goal of this work is to study the performance of a new set of 3D-microdetectors for microdosimetry measurements in the heterogenous dose deposition produced by pMBRT.

The new 3D-microdetectors used are a type of silicon diode with a 3D-cylindrical electrode etching with an inner volume that matches a sensitive volume similar to a subcellular structure. The complete ICPO beamline and pMBRT irradiations setup as well as 3D-microdetectors were modelled using GATEv7.0 simulations. A clinically relevant energy (100 MeV) was used. For minibeam generation the brass multi-slits collimator used in the experiments was modelled. The proton beam average energy was modulated with an in-house wedge system formed by two equal 10° angle wedges made of Lucite.

Preliminary results show that this new device is useful to microdosimetry characterization at nominal clinical fluence rate. Ongoing microdosimetry measurements are being performed at ICPO


A medical ethics ranking system for allocation of scarce proton therapy resources

P. Kabolizadeh1, P. Reitemeier2, M. Navin3, D. Hamstra1, J. Anderson4, C. Stevens1

1William Beaumont Hospital, Radiation Oncology, Royal Oak, MI, USA, 2William Beaumont Hospital, Clinical Ethics, Royal Oak, MI, USA, 3Oakland University, Ethics, Royal Oak, MI, USA, 4William Beaumont Hospital, Hematology Oncology, Royal Oak, MI, USA

Introduction: A single-room proton facility operates at full capacity of 16 hours daily. A triage system was developed to optimally allocate this scarce resource for maximal patient benefit. Prostate patients were excluded as only limited spots were allocated to them.

Methods: In cooperation with members of the clinical ethics and Hem/Onc, a multi-domain scoring system was created to help allocate available proton starts to patients with greatest clinical benefit. Patients were prospectively peer-reviewed during proton rounds in a multidisciplinary manner. In order to look at the feasibility, this was applied to new proton starts and they were evaluated according to the highest composite score based on anticipated clinical benefit (1-6pts), expected survival duration (0-8pts), strength of evidence (1-2pts), KPS (0to-2pts), and enrolled in research protocol (1-3pts).

Results: Fifty-one patients (43adult and 8pediatric) were evaluated from September through December 2018 while machine was at capacity. Median and mean composite scores for all patients were 11 and 11.55 respectively (range4-21,SD4.42). Median and mean scores was 20 and 19.25 respectively for pediatrics (range16-21,SD1.48). Median and mean scores for adults were both 10 and 10.12 respectively (range4-17,SD3.07). All pediatric and adult patients with high scores started treatment in a timely fashion. Approximately two potential proton patients per month were diverted to other modalities due to low scores and unavailable proton starts, not including those denied by their insurer.

Conclusion: This system would enable patients with strong levels of clinical benefit, evidence, and expected survival to initiate treatment more expeditiously than those for whom proton benefits are less clear.


IMRT for breast and lymph node irradiation: A comparative dosimetric study between tomotherapy, VMAT and proton therapy

L. Bartolucci1, C. Adrien1, M. Lejars2, M. Vaillant2, A. Fourquet1, M. Robillard1, E. Costa1, A. Mazal2, F. Goudjil2, Y. Kirova1

1Institut Curie, Radiation Oncology, Paris, France, 2Institut Curie, Radiation Oncology, Orsay, France

Purpose: To compare all treatment options available in our institution in terms of volume coverage and organs at risk (OAR) sparing.

Material and Methods: We studied 10 patients treated for breast cancer (BC) with lymph node (LN) involvement. Prescription dose was 63 Gy to the tumor bed, 51.8 Gy to the whole breast and 50.4 Gy to the LN in 28 fractions. Helical Tomotherapy (HT) with a field width of 2.5 cm (HT_FW_2.5) was the treatment used in these 10 cases. HT_FW_5, or Volumetric Modulated Arc Therapy VMAT and proton therapy with Pencil Beam Scanning (PT_PBS)plans were designed and compared to the clinically approved plan (HT_FW_2.5) using dosimetric indices for OAR (Dmax for the spinal cord, Dmean for the heart, both lungs and contralateral breast) and PTV (D95%, D2% and Homogeneity Index). A paired Student's t-test (α=0.05) was used to cross-check all plans.

Results: Results reported in Table 1 show that PT_PBS plans show that an excellent PTV coverage can be maintained along with significantly lower doses to the heart, contralateral lung and contralateral breast.

Conclusions: Our results showed that PT_PBS treatment should be considered in the near future as it showed great potential benefit to lower the risk of side effects. Prospective studies are needed to evaluate the clinical impact of this treatment.


Investigation on FLASH therapy using a high frequency linac for protons

A.M. Kolano1, A. Degiovanni2, J.B. Farr1

1AVO-ADAM, Medical Physics, Geneva, Switzerland, 2AVO-ADAM, Physics, Geneva, Switzerland

Background and Significance: Recent in-vivo studies demonstrated that electrons delivered at high dose rates within 0.5 s (FLASH) to cancerous tissues inhibit tumor growth as well as with conventional therapy, but significantly sparing surrounding healthy tissues.

Specific Aim: In this study, we investigated the possibility of using proton pencil beam scanning (PBS) for uniform FLASH irradiations using a pulsed proton linac and considered the beam parameters needed to achieve FLASH dose rates.

Methods: A commercial treatment planning system (RaySearch Labs AB, Stockholm; model RayStation; version 6.99R) was used to perform treatment plan calculations to deliver 10 to 40 Gy uniform doses to 2 cm2 targets at various depths. Parameters from a commercial proton linac (Advanced Oncotherapy plc, London; model LIGHT) were considered to deliver the needed doses within the 0.5 s FLASH time limit at a pulse rate of 200 Hz. High dose rate requires a high number of protons per pulse; therefore, in our study, we consider 200 to 800 Mp (mega proton) per pulse, assuming 1 pulse per spot.

Results and Conclusions: Our analytical study shows that LIGHT could deliver high doses within 0.5 s with dose rates of the order of 40 Gy/s and the same time structure of 3 GHz conventional electron linacs. Optimized parameters such as spot spacing, weight and size can aid in decreasing the delivery time to produce the FLASH effect with protons using a clinical machine setting. The LIGHT Solution and its successive evolutions are subject to conformity assessment and market authorization.


Beamline optimization studies for small animal irradiation at clinical proton therapy facilities

S. Kundel1, M. Pinto1, N. Kurichiyanil1, M. Würl1, F. Englbrecht1, M. Hillbrand2, J. Schreiber1, K. Parodi1

1Ludwig-Maximilians-Universität München, Department of Medical Physics, Garching b. München, Germany, 2Rinecker Proton Therapy Center, Medical Physics, München, Germany

Interest in proton therapy is rapidly emerging. However, the biological effects of protons interacting with human tissue are not completely understood. Preclinical studies may play a major role in tackling those questions. Proton beamlines tuned for clinical use usually do not provide beam properties required for small animal irradiation. Building or adapting a beamline exclusively for such studies can be costly and unpractical. The project SIRMIO aims at developing a small-animal irradiation platform for deployment in standard proton therapy centers. A beamline study based on Monte Carlo simulations and input from experimental data was conducted to obtain proton beams with energies ranging from 20 up to 75 MeV using a set of magnets allowing for tunable spot sizes down to less than 1 mm FWHM. Several arrangements of doublets, triplets and quadruplets of either permanent or electromagnets were studied, coupled with passive elements such as degraders and collimators to yield suitable conditions for proton energy, spot size and shape, and beam emittance. Dose homogeneity and dose delivery times for typical small-animal irradiation were assessed using simulation and planning data. Using the case of a 30 MeV proton beam as an example, the results showed that entrance-to-peak and plateau-to-peak ratios of ∼40% and ∼52%, respectively, can be achieved. When compared to other beamline designs consisting of passive elements only, fluence of secondary neutrons was reduced to ∼10%. Supported by ERC grant 72553.


The LARA Radiobiology Facility for the Center for the Clinical Application of Particles

A. Kurup1

1Imperial College London, Physics, London, United Kingdom

The Center for the Clinical Application of Particles (CCAP) is an interdisciplinary collaboration to develop the technologies, systems, techniques and capabilities necessary to deliver a paradigm shift in the clinical exploitation of particles. The CCAP aims to deliver a broad program of measurement of the radiobiological effect of particle beams and systematic studies of radiobiological mechanisms using a laser-driven ion source. The design of the Laser Accelerator for Radiobiological Applications (LARA) facility will be presented.


Flash radiotherapy: A look at ultra-high dose rate research and treatment plans

A. Magliari1, J. Perez1

1Varian Medical Systems, Medical Affairs, Palo Alto, CA, USA

Research is ongoing in the field of ultra-high dose rate radiation therapy. Early pre-clinical studies show normal tissue sparing while not compromising tumor control when the beam-on-time for the normal tissue is under one second.

These very exciting discoveries, however, require dose rates of 40Gy/sec - 120Gy/sec (or 240,000cGy/min - 720,000cGy/min). Proton therapy presents the most immediate opportunity for translation of Flash radiotherapy into human patients.

This talk will focus on covering most of the recent research findings to-date (high-level literature review with photos) and then follows with an overview of some of the treatment planning concepts which could be employed to make proton Flash treatments a reality for humans.


30MeV accelerator-based BNCT system and the current status of its clinical trials in Japan

S. Masui1, T. Asano2

1Sumitomo Heavy IndustriesUSA- Inc., Business Development, Allentown, PA, USA, 2Stella Pharma Corporation, Management, Osaka, Japan

Since the 1950s, numerous global clinical attempts at boron neutron capture therapy (BNCT) utilizing research reactors have been made. An accelerator-based (AB) neutron source is imperative for future hospital use because regulations for reactors are too strict to install and operate in a hospital environment. Accordingly, considerable developmental efforts for AB neutron sources are being made around the world. In this presentation, the first commercial AB-BNCT system developed by Sumitomo, which is used for human treatments, is reported.

BNCT consists of two key components. The first is an epithermal neutron source and the second is a boron compound. The Sumitomo system employs a 30MeV proton cyclotron and a beryllium target as a neutron source. The neutron energy generated at the target reaches up to 28MeV and is then moderated down to epithermal range, the energies of which are appropriate for human irradiation.

In 2012, Sumitomo and Stella Pharma Corporation (Stella) started phase I clinical trials for brain tumor and head and neck cancer using a boron compound, boronophenylalanine (INN : borofalan(10B)), provided by Stella, and the recruitment and irradiation of our phase II clinical trials completed in 2018.

A medical device application process is now under way for the first time in Japan and its regulatory status is also presented here.


PROBE: Proton Boosting Extension for imaging and therapy

H. Owen1, G. Burt2, R. Apsimon2, S. Pitman2

1University of Manchester, School of Physics and Astronomy, Manchester, United Kingdom, 2University of Lancaster, Engineering, Lancaster, United Kingdom

The ProBE project aims at accelerating protons from a particle therapy cyclotron to the c.330 MeV required for proton tomography of adults. To obtain the c. 50 MV/m gradients required to achieve 100 MeV gain in a suitably short distance, we propose the use of an S-band side-coupled standing-wave structure with novel properties. In this poster we discuss the progress from initial designs to the current prototype due to be tested at CERN. This linac may also be used to make linac-based proton therapy systems smaller than is presently possible.


Evaluation of a new experimental setup for radiobiology experiments at the E1 area of the ELI-NP building using FLUKA

M.A. Popovici1, R. Vasilache2

1Bucharest Polytechnical University, Faculty of Applied Sciences, Bucharest, Romania, 2Canberra Packard, Management, Bucharest, Romania

Currently there are two state-of-art research infrastructures in Romania, ELI-NP and CETAL, which use ultrahigh power lasers (10 PW in the first case, 1 PW in the second) for a wide array of research activities. One of the declared purposes of the ELI-NP project is to explore the possibility of developing new techniques in proton therapy by using laser-accelerated beams. However, it is highly probable that some of the initial experiments will be directed towards gaining more insight into the radiobiology of proton therapy and the factors that influence the relative biological effectiveness of the beam.

The present paper analyses the feasibility of such radiobiology experiments at the E1 area of the ELI-NP building, using proton beams with maximum energies of up to 500 MeV. The FLUKA code is used to simulate a case in which a proton beam with 400 divergence is collimated on a 10-cm-diameter exit window. The beam is used to irradiate a parallelepipedal water phantom placed in air at a distance of 10 cm from the window. The phantom has a 20x20 cm2 cross area and a depth of 10 cm. We present the results regarding beam homogeneity and symmetry at the phantom entrance side, as well as the depth dose curves and the depth LET curves, both for primary protons and for all ionizing particles. We conclude by showing how this information can be used for designing the setup of radiobiology experiments at an ultrahigh power laser area.


Neutron capture enhanced particle therapy (NCEPT): An opportunistic dose amplification for particle therapy via capture of internally generated thermal neutrons

M. Safavi-Naeini1, A. Chacon2, N. Howell1, R.J. Middleton1, B. Fraser1, S. Guatelli2, L. Rendina3, N. Matsufuji4, M.C. Gregoire1, A. Rosenfeld2

1Australian Nuclear Science and Technology Organisation ANSTO, Human Health, Lucas Heights, Australia, 2University of Wollongong, Center for Medical Radiation Physics CMRP, Wollongong, Australia, 3The University of Sydney, Chemistry, Sydney, Australia, 4National Institutes for Quantum and Radiological Science and Technology NIRS-QST, Medical Physics, Chiba, Japan

Neutron Capture Enhanced Particle Therapy (NCEPT) is an enhancement to proton and heavy ion therapy being developed by the Australian Nuclear Science and Technology Organisation (ANSTO) and the University of Wollongong, Australia. NCEPT amplifies the impact of particle therapy by capturing thermal neutrons - a byproduct of treatment, produced in and around the target - inside cancer cells to deliver extra dose to the tumor. NCEPT uses drugs currently used or in development from the field of neutron capture therapy, which concentrate in cancer cells and are optimized for thermal neutron capture. NCEPT delivers the prescribed radiation dose to the tumor while exposing healthy tissue to less radiation compared to standard particle therapy. It also delivers significant dose to nearby satellite tumors too small to be visible to cancer imaging systems.

The feasibility of NCEPT is supported by Monte Carlo simulations evaluating thermal neutron fluence for a simple uniform treatment plan (Figure 1). In this work, we present the first in-vitro experimental results obtained with carbon and helium beams at HIMAC (National Institute for Quantum and Radiological Science, Japan) in July 2018. For primary ion doses of the order of 3 Gy delivered to cultured human glioblastoma cells (T98g) treated with clinically-feasible concentrations of 10B and 157Gd-based neutron capture agents, cell proliferation was reduced by approximately 80% compared to untreated controls.

Results obtained with the carbon beam are shown in Figure 2. These results provide strong experimental evidence supporting the proposed method and potential for improving treatment efficacy and reducing side-effects.


Determining the number of proton facilities required for optimal care

K. Sikora1, J. Pettingell2

1Proton Partners International, Medical, LONDON, United Kingdom, 2Proton Partners International, Physics, London, United Kingdom

Radiotherapy is currently used in 50% of cancer patients. Proton therapy (PT) allows more precise delivery of radiotherapy and can reduce the long-term damage to normal tissues surrounding a cancer. But it is expensive, costing two to ten times more than traditional radiotherapy, depending on the system.

Meaningful, large scale, randomized trials with protons versus photons are challenging and are likely to be inconclusive. Instead, the pre-treatment comparison of PT versus state-of-the-art Intensity Modulated Radiotherapy (IMRT) in individual patients using pre-set metrics of plan quality will be used to decide whether PT has any advantage. This assessment can now be made objectively by treatment planning software systems. Payers, government and insurers, will use set criteria to assess the value of PT in an individual using a comparative equation incorporating tumor control, early and late toxicity and overall lifetime costs of care. Such analyses will determine logically the level of the therapeutic plateau in the relationship of cost to gain in clinical outcome.

Here, we have carried out an extensive meta-analysis of published estimates for the optimal utilization of PT in radical radiotherapy. The range is wide from 1% to 40%. Recent policy studies from several European countries indicate a 10 -15% conversion to PT in patients treated with radical intent. Based on the world literature, one PT facility treating 500 new patients a year for a population of 4m seems a reasonable estimate for optimal cancer care.


Modelling to rapidly compare photon and proton dose distribution in individual patients

K. Sikora1, M. Crocker2

1Proton Partners International, Medical, LONDON, United Kingdom, 2Proton Partners international, Information technology, London, United Kingdom

Our aim is to produce a model that allows a comparison of images after treatment with different radiation modalities. This reduces the requirement for full clinical double planning and to plan only those patients that show evidence of likely benefit from protons after a quick, low-cost and semi-automated assessment process.

Our approach is to first produce a model showing the whole process outside the clinical environment. These results are not for any clinical purpose. This approach has allowed us to modularize the entire process. Some elements have slotted in applications that are fulfilling their function very well. While we still have some element of human input within the pathway, we continue to build scripts and functions to fulfil complete automated delivery. We now have a semi-automated end-to-end process that can feed in an image and produce a pdf report at the far end. At this stage, the quality and usability in a clinical environment was not an objective.

This approach has allowed us to run two parallel projects. One investigates what automation we can use to aid clinical workload and processes. The second examines ways of refining the model to fully automate this process using not only defined images but also DICOM-RT feeds. Automated treatment planning is rapidly evolving. We will demonstrate our double planning comparative model which effectively determines the normal tissue complication probability (NTCP) from both protons and photons rapidly and automatically from PTV and OAR outlines.


Disaster recovery planning for a proton therapy network

K. Sikora1, M. Crocker2, A. Saplaouras3

1Proton Partners International, Medical, LONDON, United Kingdom, 2Proton Partners International, Information Technology, London, United Kingdom, 3Proton Partners international, Physics, London, United Kingdom

We are building a global network of proton centers using single gantry systems in the UK and abroad. All are linked through a central server in London Docklands with appropriate backup. Most hospital and community radiation systems have on-site based IT solutions. We currently support these systems, but they can give rise to a number of critical issues in the event of local failure from whatever cause. We describe here our networked solution for IT providing LINAC and proton radiotherapy as well as chemotherapy. We will describe our strategy for:

  • Disaster Recovery (DR) for complete loss of power, fire, flood or structural collapse

  • Loss of radiation equipment from hardware failure or explosion

  • Loss of cyclotron function

  • Failure of local IT systems

Most hospital multiple unit LINACS are located on the same site, making them still vulnerable to disaster events. Single gantry proton systems have no substitution potential on the same site but networked IT allows immediate patient transfer to an operational site.

Moving the key applications to a secure central data center can serve many sites, which with a little adjustment in processes to enable each site to act as a backup and provide an emergency resource. With this IT concept, we provide a robust or viable DR plan that takes allows continuity of patient care in the event of a catastrophic failure at any single site.


Electron beam radiobiology up to 1 GeV and 50 Gy/sec at the Berkeley Lab Laser Accelerator (BELLA) Center

A. Snijders1, J.H. Mao1, K. Nakamura2, J. Bin2, A. Gonsalves2, H.S. Mao2, S. Steinke2, M. Roach III3, W. Leemans2, E. Blakely1

1Lawrence Berkeley National Laboratory, Biological Systems & Engineering, Berkeley, CA, USA, 2Lawrence Berkeley National Laboratory, Accelerator Technology & Applied Physics, Berkeley, CA, USA, 3University of California- San Francisco, Radiation Oncology - Helen Diller Cancer Center, San Francisco, CA, USA

Laser-generated ion beams can provide much higher doses and dose-rates than conventional ion sources, and preclinical tests have demonstrated clinical advantages of ultra-high doses and dose rates in eradicating tumors. The Lawrence Berkeley National Laboratory is working with the University of California, San Francisco to develop an experimental platform for investigating radiobiological effects of laser-accelerated electron and ion beams for the treatment of cancer.

Preliminary published data indicate an advantageous differential response between tumor and normal tissues at ultrahigh dose rates with sparing of normal tissue. We are investigating the mechanisms underlying this differential response, and are comparing effects to BELLA-accelerated electron reference beams.

We are focusing on radioresistant prostate tumors since they are hard to treat with conventional methods. We therefore selected three human prostate tumor cell lines, and one normal human prostate line. We are beginning with in vitro studies, but plan future studies with tumor cells implanted in mice.

We will present preliminary data comparing survival for two different endpoints (colony-forming ability and MTT) after exposure to 300kVp X-rays, and to low-energy (∼10MeV) versus high-energy (1GeV) electrons, over a dose range of 1-10 Gy, and a dose-rate range of from 1 Gy/min up to 50 Gy/sec. We anticipate that high repetition rate petawatt laser plasma accelerator performance will allow future tailoring of electron and particle energy and numbers to specific applications in the field of cancer cell biology for research users of the BELLA Center. Supported by LBNL Laboratory-Directed Research and Development funding under Contract No. DE-AC02-05CH11231.


Energy sweep compact rapid cycling hadron therapy (ESCORT)

K. Takayama1

1High Energy Accelerator Research Organization, Accelerator Laboratory, Tsukuba, Japan

A novel concept of hadron therapy allowing tracking irradiation on a moving and deformed tumor target has been proposed (Ken Takayama, “ESCORT”, presented at New Technologies in Hadron Therapy Workshop, IEEE NSS-MIC 2018). The concept is characterized as follows;

  1. Its beam driver is a fast cycling induction synchrotron (20 Hz), where a fully stripped heavy ion beam is delivered from the laser ablation ion source, the injected ion beam is captured in the barrier bucket and accelerated with the induction step voltage, a beam spill is continuously extracted by the energy sweep extraction method combining the programed barrier bucket leak and the lattice characteristics with the localized large momentum dispersion function (Leo K.W et al., Phys. Rev. Accel. & Beam 19, 042802, 2016).

  2. A combination of beam profile monitors and the full-body Liq. Xe 3g camera is used to obtain the dose profile/position in depth by detecting prompt gs. The accompanied X-ray camera also catches the position/profile of the tumor target. Signals are quickly processed in computers and the irradiation errors are found at 20 Hz.

  3. The errors signals are transferred to the switching power supply energizing the induction cells to adjust the extraction timing. The position error signals are feedbacked to the fast deflecting magnet, which is excited with a different current every cycle so as to realign the scanning beam spot on the desired position.


Governance and procurement process for proton beam therapy (PBT) equipment in the new National Cancer Center Singapore (NCCS) building

T.S. Tan1, J.T.S. Wee2, J.K.L. Tuan2, K.W. Fong2, M.L.C. Wang2, J.S.H. Quah3, N.C.W. Tay4, J.C.L. Lee2, J.K.H. Lim5

1National Cancer Center Singapore, Proton Therapy PMO, Singapore, Singapore, 2National Cancer Center Singapore, Division of Radiation Oncology, Singapore, Singapore, 3Singapore Health Services, Group Finance, Singapore, Singapore, 4National Cancer Center Singapore, NCCS Executive Office, Singapore, Singapore, 5National Cancer Center Singapore, Operations, Singapore, Singapore

Purpose: To describe the governance and procurement process for Proton Beam Therapy (PBT) equipment in new National Cancer Center Singapore (NCCS) building.

Methods: Approval to establish a proton beam therapy facility in the new NCCS building at Outram Campus was obtained in 2012. A Board-level committee was formed to provide governance over the procurement process. Under this board, the project committee was formed to manage the procurement process. A two-stage procurement process was adopted. A Request-For-Information (RFI) was first called. Potential Proton Beam Therapy Equipment Vendors (PTEVs) provided base information about their equipment and their company strengths and profiles. Shortlisted PTEVs were invited to participate in the second-stage Request-For-Proposal (RFP) wherein detailed proposals were submitted. Proposals submitted by shortlisted PTEVs were evaluated by 7 separate evaluation teams namely: Technical, Service, Interface (Building), Contract mark-up, Organization, Commercial, and Price. To ensure that the merits of the proposals by PTEVs were not influenced by price, a two-envelope system process was employed within the RFP exercise. The price proposal was not evaluated until the 6 other teams had completed their assessment based on technical/functional of the vendors' proposals. Down-selected PTEVs were invited to improve their offers in a Best-and-Final-Offer (BAFO) exercise.

Results: A PTEV was selected to be the Preferred PTEV. A second PTEV was selected to be the Reserve PTEV.

Conclusion: The procurement process for PBT equipment in the new NCCS has been conducted in a transparent and open manner as described above.


Method to prevent accidental X-ray exposure to straying patients and staff during in-room imaging at National Cancer Center Singapore

T.S. Tan1, M.L.C. Wang2, A.A. Oei1, J.M. Tan1, J.C.L. Lee2, S.Y. Park2, W.W.L. Chow2, Y.B. Omar2, P.G. Chew2

1National Cancer Center Singapore, Proton Therapy PMO, Singapore, Singapore, 2National Cancer Center Singapore, Division of Radiation Oncology, Singapore, Singapore

Purpose: To ensure safety in proton therapy processes and prevent accidental X-Ray exposure to straying patient and/or staff from entering the treatment room during in-room imaging in the new Proton Therapy Center at National Cancer Center Singapore whilst maintaining safety, show, and efficiency.

Methods: The new NCCS Proton Therapy Center will have in-room imaging capability for each of its four full rotating gantries. In-room imaging enables therapists to image the patient without needing to walk out of the treatment room, thereby increasing efficiency. As part of safety treatment doors will be left opened during patient setup and imaging as they are interlocked with the PBT equipment. No proton beam can be delivered whilst the doors are kept open. However, leaving the doors open runs the risk of patients and staff straying into the room during imaging, thereby exposing them to unnecessary x-rays.

Results: A digital Area Status Display (ASD) along with retractable crowd barrier will be strategically placed in the maze to deter and warn patients and staff from straying into the room. Treatment doors can remain open to ensure safety of therapists in the room and maximize workflow efficiency. Aesthetic interior design will not be compromised.

Conclusion: The method to be employed in the new Proton Therapy Center at the new NCCS building would allow NCCS to maintain safety for its staff and patients, and promote efficiency in the overall treatment process.


Proton quality assurance through the Global Harmonisation Group

P. Taylor1, J. Lee2

1UT MD Anderson Cancer Center, Radiation Physics, Houston, USA, 2East and North Hertfordshire NHS Trust, Radiotherapy Trials Quality Assurance Group, Northwood, United Kingdom

The Global Harmonisation Group for Quality Assurance in Clinical Trials (GHG) has established a subcommittee for proton quality assurance. The goal of the subcommittee is to combine particle therapy and QA expertise from around the world for the purpose of harmonizing clinical trial credentialing (including dosimetry audits) of particle therapy centers.

The subcommittee consists of members from the European Organisation for Research and Treatment of Cancer (EORTC), the US Imagining and Radiation Oncology Core (IROC), the Japan Clinical Oncology Group (JCOG), the UK Radiotherapy Trials Quality Assurance Group (RTTQA), the Trans-Tasman Radiation Oncology Group (TROG), the International Atomic Energy Agency (IAEA), and the Australian Clinical Dosimetry Service (ACDS).

The subcommittee members have shared details of their existing proton QA programs to review where there are gaps in services and room for growth and collaboration. Three working groups have been established to focus on specific components of proton therapy review: (1) Dosimetry/Equipment QA, (2) Treatment Plan Assessment, and (3) Patient Positioning, Immobilization, IGRT and Treatment Review. Dosimetry and Equipment QA have been developed by individual QA groups and the GHG are comparing the various methods to ensure equivalence. We are collaborating on the development of anthropomorphic phantoms, funded through JCOG. The working group on Treatment Plan assessment is developing consensus guidelines for case review of proton plans.

The standardization of such practices will enable global collaboration for proton clinical trial research, helping to boost the statistical power of clinical trials.


The High-Current Sumitomo Superconducting Isochronous Cyclotron (sc230) for proton therapy

T. Tsurudome1, M. Hirabayashi2, H. Tsutsui3, J. Yoshida1, N. Takahashi1, N. Kamiguchi1, A. Hashimoto1, T. Tachikawa2, Y. Mikami1, Y. Kumata4

1Sumitomo Heavy Industries- Ltd., Technology Research Center, Yokosuka, Japan, 2Sumitomo Heavy Industries- Ltd., Industrial Equipment Division, Niihama, Japan, 3Sumitomo Heavy Industries- Ltd., Industrial Equipment Division, Tokyo, Japan, 4Sumitomo Heavy Industries- Ltd., Corporate Technology Management Group, Tokyo, Japan

Sumitomo Heavy Industries, Ltd. is newly developing a superconducting isochronous cyclotron (SC230) for a new proton therapy system which is low cost, compact and ultra-high current beam. The beam energy, the maximum beam current, and the isochronous magnetic field of the new cyclotron are 230 MeV, 1000 nA, and 4 T respectively. The ultra-high beam enables to deliver the high dose to the whole volume of a moving target within one breath-hold by means of fast line scanning method.

A superconducting magnet is composed of two NbTi coils and yoke. NbTi coils are conduction-cooled by four 4 K Gifford-McMahon cryocoolers without liquid helium. The yoke weight is about 65 tons and diameter is 2.8 m, which is the smallest AVF cyclotron for this purpose. Inside the cyclotron, two RF cavities are in deep valleys. Another two valleys are used for beam monitoring and vacuum pumping. Extraction elements are one electrostatic deflector, two passive magnetic channels. Around the beam extraction radius, eight harmonic coils are equipped for a precessional extraction method. By adopting the precessional extraction method, simulated extraction efficiency is more than 70 %.

The superconducting magnet has been manufactured and confirmed to generate 4 T in 2018. We are currently measuring a magnetic field distribution and manufacturing other components of the cyclotron. The beam test will be performed in 2019.

Overview of the development plan and status will be presented.


Particle therapy in Singapore: Planning for a national proton beam therapy (PBT) facility

M. Wang1, E.T. Chua1, K.W. Fong1, J. Wee1, F.Y. Wong1, J. Tuan1, J. Lee1, Z. Master1, P.G. Chew1, S. Wong1

1National Cancer Center Singapore, Division of Radiation Oncology, Singapore, Singapore

Purpose: Singapore's cancer prevalence is expected to triple by the year 2030, in line with an aging population. The National Cancer Center Singapore treats 62% of the national cancer load. Expansionary plans for a new comprehensive cancer center presented the best opportunity to study the feasibility of a multi-gantry PBT facility in the new building.

Methods: Planning began in 2008. An estimated fifteen percent of patients who require radiotherapy will benefit from proton therapy. Initial case-mix was based on the Swedish estimates. Guidelines from the NHS, ASTRO and various countries were used to estimate the patient load for PBT. Modelling of throughput capacity was performed using the Manchester and various models for a multi-gantry room proton center. Based on these, a 4-gantry PBT system was proposed, for a steady-state treatment capacity of between 800-1000 patients a year, treating within 1.5 to 2 shifts. Ramp-up strategies of 3 to 7 years to steady-state were studied. A fixed-beam room was also planned for research.

Results: Government approval for the PBT facility was given in 2012. The new center will be operational in 2020-21 with 8 LINACs, with the PBT facility starting a year later with 2 gantries. Fully operational, the new center will also have 17 LINAC bunkers and 2 brachytherapy suites.

Conclusion: There are several levels of governance within the healthcare cluster and the Ministry of Health Singapore, which is the government body regulating the utility of PBT in Singapore. Clinical indications as well as healthcare financing for PBT will also be regulated.


Breast cancer proton beam therapy and proton CT on a rotating platform instead of a gantry

J. Welsh1, C. Hentz1, M. Pankuch2, S. Schmidt2, F. DeJongh3

1Loyola University Stritch School of Medicine, Radiation Oncology, Maywood, IL, USA, 2Chicago NW Medicine Proton Center, Radiation Oncology, Warrenville, IL, USA, 3Proton VDA, Proton Radiography, Batavia, IL, USA

At our proton therapy center, a large fraction of patients will be either treated on or waiting for availability of the gantry. As we possess only one room that houses a gantry, this leads to a practical bottleneck. We are exploring high-quality, cost effective alternative treatment techniques to decompress the clinical load on our single gantry.

Based on our prior clinical experience with treatment in a standing or seated position on a rotating platform at the Fermilab Neutron Therapy Facility, we wanted to explore the feasibility of this concept at our proton center. Specifically, we aimed to estimate the potential of this alternative as a means of reducing the number of breast cancer patients treated with our gantry. We gathered data on breast cancer patients treated on the gantry from June-August 2018 and determined the proportion of cases that required a “couch kick”. Of all breast cancer cases treated in this time interval, only 16% required a couch kick at all; including primary plans and boosts, this figure fell to 8%.

Because the geometry of treatment with a gantry on an unkicked table is identical to treatment with a fixed horizontal beam and the patient in a standing or seated position on a rotatable platform, we conclude that up to 92% of breast cancer patients treated with the gantry at our facility could potentially be treated on a customized, low-cost, rotatable platform as an alternative. With such a platform, proton CT can become far more feasible than gantry-based methods.


Proton arc therapy improves plan quality in the presence of range and setup uncertainties compared to intensity modulated proton therapy

Y. Xia1, A.H. Aitkenhead2, R. Appleby3, M.J. Merchant1, N.G. Burnet2, K.J. Kirkby4, R.I. MacKay2

1University of Manchester, Division of Cancer Sciences- Faculty of Biology Medicine and Health, Manchester, United Kingdom, 2The Christie, Medical Physics, Manchester, United Kingdom, 3University of Manchester, Department of Physics, Manchester, United Kingdom, 4University of Manchester, Division of Cancer Sciences- School of Medical Sciences- Faculty of Biology Medicine and Health, Manchester, United Kingdom

Proton arc therapy (PAT) is likely to offer better dose to the targets and sparing of healthy tissue than intensity modulated proton therapy (IMPT) due to larger numbers of control points. This hypothesis comes from experience with conventional radiotherapy where volumetric arc therapy (VMAT) improves dose distributions and reduces sensitivity to uncertainties compared to fixed field intensity modulated radiotherapy (IMRT) in many cases. At the moment, PAT is not in clinical practice. Several groups compared PAT plans optimized with commercial treatment planning software to IMPT in nominal cases only and showed promising benefits.

Since proton therapy is sensitive to treatment uncertainties, this study aims to compare PAT to IMPT plans not only in the nominal cases but also as results of 2 kinds of treatment uncertainty (CT calibration and set up errors). We choose to work in 2 dimensions with an in-house Python optimizer as this reduces complexity, offers flexibility to explore novel optimization methods and gives results applicable in 3 dimensions. The cases chosen were a unilateral head & neck (H&N), a bilateral H&N and a skull base chordoma.

Table 1 shows the IMPT and PAT plan metrics for the unilateral H&N case as an example. The results indicate that PAT offers higher target conformality and homogeneity albeit at the cost of low dose levels to larger volumes of healthy tissue in nominal and uncertainty scenarios than IMPT. This suggests that PAT has the potential to improve dose distributions and reduce sensitivity to uncertainties compared to IMPT.


Proton ready: Easing the uncertainty with end to end testing

H. Young1, V. Hughes1

1The Christie NHS Foundation Trust, The Christie PBT Center, Manchester, United Kingdom

As the first NHS service in the UK to deliver high-energy proton beam therapy (PBT) treatments to patients, it was of paramount importance to ensure time between commissioning and first treatment delivery was utilised effectively by the multi-disciplinary team (MDT; Physics, Radiographer and clinicians).

The UK care quality commission states that NHS services should be safe, caring, effective and well lead1report. This coupled with the requirement of the PBT service to report to NHS England and prove service readiness which met a large number of quality standards with a locally established competent, well informed and practiced team2report. A project plan was therefore devised to ensure that the proposed PBT patient pathway was fully tested and each stage in the pathway had associated procedural and quality documents.

Following from applications training, 8 patient pathways were identified and during a 5-week period between October and December 2018 the PBT processes were tested. Tested areas included (but not limited to):

  • Referral to MDT meeting

  • Paperless processes and scheduling

  • PBT Treatment delivery, including imaging to establish routine workflow

  • Quality management system documents

  • Staff training

  • Contingency / Machine breakdown processes

  • End of treatment activities

End to end testing followed the Plan-Do-Check-Act cycle3report to track and test workflow and changes. The Christie will share our experience of the end to end testing process, to assist in planning and future development of new centers. Providing examples of how we utilised expertise of different specialist teams in each aspect of the process, to define workflow, share learning and decision making. 1) 2) 3)


Feasibility study to using Si detector for secondary radiation monitoring during proton therapy applications

M. Alsulimane1,2, C.A. Barajas1, J. Taylor1, G. Casse1, A. Omar3, S. Burdin1

1University of Liverpool, Department of Physics, Liverpool, United Kingdom, 2King Abdulaziz University, Department of Physics, Jeddah, Saudi Arabia, 3Military Technical College, Department of Nuclear Engineering, Cairo, Egypt

Nowadays, there is a rapid increase in the number of proton therapy centers worldwide due to proton has significant benefits over conventional photon therapy, delivering a large dose to the tumor and no dose to the healthy structures beyond. However, one of the concerns about proton therapy is the secondary radiation that is created during treatment. Secondary radiation created as a result of proton interactions within the human tissue depends on the target material, the beam energy and the delivering technique which in turn may increase the probability to develop secondary cancers in the surrounding tissues. Therefore, the aim of this research is to investigate, monitor and track the dose distribution of protons and associated secondary radiation, neutrons and gammas, when delivering the prescribed dose to the targeted cells.

In this project we using Geant4 simulation toolkit to simulate the proton beam and its interactions with a water phantom and silicon detectors in it. The water phantom contains two silicon pixel sensors fully submerged in the water and located in the main path of the proton beam in order to track the primary proton particles and measure the Bragg peak by means of the particle energy loss in the sensors. On the phantom edge there are two sandwich sensors which involves two planar silicon diodes separated with LiF film as a neutron converter layer to increase the thermal neutron capture probability to measure the secondary radiation in the form of neutrons generated in the water volume of the phantom.


Concomitant rectal spacer and endorectal balloon in proton beam therapy for localized prostate cancer

C. Boon1, J. Lester2, A.J. Thomas2, A. Khan2, L. Huthart2, K. Leaver2, J. Lambert2, J. Pettingell2, J. Snell2, A. Warlow2

1Clatterbridge Cancer Center, Oncology, BIRKENHEAD, United Kingdom, 2Rutherford Cancer Center South Wales, Clinical Oncology, Newport Wales, United Kingdom

Background: In prostate radiotherapy, rectal displacement with either rectal spacer or endorectal balloon (ERB) has been shown to reduce both treatment toxicity and intrafractional shifts. In proton beam therapy (PBT) there is also potential benefit from immobilizing the rectum and prostate relative to the pelvic bones though which the treatment beams pass. In our center, prostate cancer patients are implanted with the BioProtect biodegradable rectal spacer balloon prior to initial planning scans. A MEDRAD Pro-Tekt Endorectal balloon is also inserted at each scanning and treatment session. We aim to investigate the feasibility of and clinical and dosimetric advantage from concomitant rectal spacer and ERB in pencil-beam-scanning PBT for prostate cancer.

Methods and Results: The data for the first 10 prostate cancer patients has been analyzed.

CT, MRI, and daily cone beam CT images throughout the course of treatment and post treatment MRI scans were used to assess:

  1. Intrafractional shifts by measuring the distance from the prostate to standard pelvic bone reference points

  2. Changes in rectal volume

  3. Distance and direction of travel of the anterior rectal wall

  4. Bladder filling status

  5. Bio-degrading of rectal spacer balloon

Dosimetric analyses of target and organs at risk (OARs) are also presented. Patient reported outcomes and side effects were assessed using the common terminology criteria for adverse events (CTCAE) and Radiation Therapy Oncology Group (RTOG) toxicity criteria during follow up.

General: New Horizons Poster Discussion Sessions


PBS plan correction for MR-guided proton therapy in the presence of in-line magnetic fields

L.N. Burigo1,2, B. Oborn3,4

1German Cancer Research Center - DKFZ, Division of Medical Physics in Radiation Oncology, Heidelberg, Germany, 2Heidelberg Institute for Radiation Oncology – HIRO, National Center for Radiation Research in Oncology - NCRO, Heidelberg, Germany, 3University of Wollongong, Center for Medical Radiation Physics - CMRP, Wollongong, Australia, 4Wollongong Hospital, Illawarra Cancer Care Center - ICCC, Wollongong, Australia

A novel technique combining magnetic resonance imaging (MRI) and proton therapy may allow fully exploiting the potential of high dose conformation in proton therapy (Raaymakers et al 2008). It should provide high soft tissue contrast imaging of patients during treatment, reducing geometrical uncertainties and related treatment margins. However, the magnetic field of the MRI scanner impacts the proton beam delivery (Oborn et al 2015). This contribution presents two strategies to modify the proton pencil beam scanning (PBS) plans to correct for the presence of an in-line magnetic field. The first strategy introduces changes within the dose calculation engine of the treatment planning system (TPS) to account for the effect of the magnetic field during plan optimization. The second strategy simply applies an energy-dependent rotation offset of beam spots during plan delivery. We considered fringe and imaging magnetic fields of 0.5, 1.0 and 1.5 T adapted from a realistic split bore MRI scanner. Plan delivery for a water phantom, liver tumor and prostate cancer were simulated with Monte Carlo simulations using TOPAS (Perl et al 2012). Results clearly indicate that modifications are required to deliver acceptable plans. The degradation of the plan quality depends on the field strength, tumor site, shape, and the field configuration. Plans with both modification strategies are equivalent to the reference plans without magnetic field. In summary, the workflow for proton PBS can be adapted for precise plan delivery in MR-guided proton therapy in the presence of in-line magnetic field.


FLASH proton dosimetry and achievable dose rates in a scanned proton beam for geometrical fields

S. Safai1, F. Belosi1, A. Fredh1, S. van de Water1, D. Weber1, A. Lomax1

1Paul Scherrer Institute, Center for Proton Therapy, Villigen PSI, Switzerland

Purpose: Dose rates above a certain threshold (> 30Gy/s) could have a protective effect on healthy tissue – the FLASH effect – but may challenge standard dosimetry procedures when such fields are delivered and measured. In this work, we investigate the performance of ionization chambers when exposed to proton dose rates in the FLASH domain for pencil beam scanning (PBS).

Method: To determine what dose rates a modern commercial PBS treatment unit can achieve when pushed to its limits for simple geometrical fields, and to examine the dose rate response of the primary beam monitor (PBM), Faraday cup measurements have been employed. In addition, the dose-rate response of a Farmer chamber has been investigated up to the maximum achievable dose rate with such a gantry. For this, under reference conditions, the Farmer chamber in water was exposed to a 10x10x5cm3 field centered at 10cm depth with different dose rates and dose levels.

Results: During PBS, pencil beam currents around 5nA at isocenter could be reached. Under these conditions, a single pencil beam could deliver up to 120Gy/s in water (figure 1). Faraday cup measurements showed no dose rate dependence of the PBM. Similarly, when the Farmer chamber was exposed to up to 100Gy/s and 8Gy, no significant dose rate dependence was observed.

Conclusions: Proton beams generated with a cyclotron, like in this work, can be considered as continuous and as such, dosimetry performed in the lower end of the FLASH domain do not appear to be particularly challenging.


Improving the dose distribution in minibeam radiation therapy: Protons vs helium ions

T. Schneider1, A. Patriarca2, Y. Prezado1

1Imagerie et Modélisation en Neurobiologie et Cancérologie IMNC, CNRS - Université Paris 11 - Université Paris 7, Orsay, France, 2Institut Curie - PSL Research University, Center de Protonthérapie d'Orsay - Radiation Oncology Department, Paris, France

Purpose: Hadron minibeam radiation therapy combines the improved dose deposition of ions with the normal tissue sparing of submillimetric, spatially fractionated beams [1,2] thus enabling safe dose escalation in the tumor. Next to protons [3,4,5], helium ions are a possible choice for minibeam radiation therapy. They offer reduced lateral scattering without the problems of nuclear fragmentation encountered with heavier ions [6,7].

Methods: Proton and helium ion minibeams of the same range have been simulated in a water phantom and in CT images of a human head. The Monte Carlo simulation toolkit GATE v8.0 [7] was used. Two configurations corresponding to beam sizes of 1 and 3 mm (FWHM) at target entrance were considered. Different minibeam spacings were evaluated. The dose and lineal energy transfer (LET) were measured in the targets.

Results: Helium ions yield an improved Bragg-peak-to-entrance dose ratio (BEDR), especially for the 1 mm beams. At equal minibeam spacing, they lead to larger peak-to-valley dose ratios. The LET was higher for helium at all depths.

Conclusion: Helium ions might present the best compromise for minibeam radiation therapy offering an improved BEDR and less lateral scattering without the possible drawbacks linked to nuclear fragmentations.

References: [1] Prezado et al., Rad. Research, 2015. [2] Dilmanian et al., PNAS, 2006. [3] Prezado et al., Med. Phys., 2013. [4] Prezado et al., Scie. Reports, 2017. [5] Prezado et al., Radiat. and Oncology, 2018. [6] Peucelle et al., Med. Phys., 2015. [7] Gonzalez et al., Med. Phys., 2017. [8] Jan et al., PMB, 2004.


Ne-MBRT: A worldwide first implementation of spatial fractionation for very heavy ions

Y. Prezado1, J. Bergs2, T. Inaniwa3, E. Hierso4, R. Hirayama3, I. Martínez-Rovira5, L. De Marzi4, N. Matsufuji3, T. Schneider1, O. Seksek1

1CNRS, Imagerie et modelisation pour la Neurobiologie et la Cancerologie, Orsay, France, 2Charité Universitätsmedizin Berlin, Institute of Radiology- Elastography, Berlin, Germany, 3QST, National Institute of Radiological Sciences, Chiba, Japan, 4Institut Curie, Orsay Proton Therapy Center, Orsay, France, 5ALBA-CELLS synchrotron, MYRAS beamline, Cerdanyola del Valles, Spain

Purpose: Very heavy ions had demonstrated their efficacy against hypoxic tumors [1]. Clinical results showed late adverse effects on tissues, which led to the discontinuation of very heavy ion therapy. Nevertheless, a renewed use by a combination with minibeam radiation therapy (MBRT) might lead to a considerable gain in tissue sparing, allowing a safe use of the therapy while profiting from its advantages [2]. Our previous Monte Carlo studies indicated favorable dose distributions, with Ne ions leading to a more balanced dose and LET distributions compared to other types of heavy ions [3].

Methods: 230MeV/n of Ne minibeams were produced and evaluated at the biology port of Heavy Ion Medial Accelerator (HIMAC), Japan. Dose distributions were measured using gafchromic films and a microdiamond detector. Irradiations of normal human fibroblast cells were performed both in conventional and in MBRT modes with the same average dose, to assess possible differences in terms of viability, pro-inflammatory cytokines production and infrared spectroscopy.

Results: The dosimetry evaluations show the feasibility of our implementation (see figure 1). Differences in terms of pro-inflammatory cytokines production between irradiation modes were evaluated.

Conclusion: We have performed the first worldwide implementation of Ne-MBRT at HIMAC. Our preliminary results show the feasibility and the interest of this approach. [1] Castro et al., IJROBP 1994. [2] Prezado et al., Scie. Reports, 2017. [3] Peucelle et al. Med. Phys. 2015


Prospective data registration in proton beam therapy nation-wide evaluation trial (PROTON-NET) using unified treatment protocols with central and onsite monitoring

H. Shirato1,2, T. Nakamura3, H. Ogino4, T. Ogino5, T. Okimoto6, H. Sakurai7, T. Akimoto8, H. Tamamura9, N. Nishimoto10, G. Proton-Net11, S. Shimizu1

1Hokkaido University Faculty of Medicine, Department of Proton Beam Therapy, Sapporo, Japan, 2Global Institute for Cooperative Research and Education, Global Station for Quantum Biomedical Science and Engineering, Sapporo, Japan, 3Southern Tohoku General Hospital, Proton Therapy Center, Koriyama, Japan, 4Nagoya City West Medical Center, Nagoya City Proton Beam Therapy Center, Nagoya, Japan, 5Medipolis Medical Research Institute, Medipolis Proton Therapy and Research Center, Ibusuki, Japan, 6Hyogo Ion Beam Medical Center, Department of Radiotherapy, Tatsuno City, Japan, 7University of Tsukuba Faculty of Medicine, Department of Radiation Oncology, Tsukuba, Japan, 8National Cancer Center East, Department of Radiation Oncology, Kashiwa, Japan, 9Fukui Prefectural Hospital, Department of Radiation Oncology, Fukui, Japan, 10Hokkaido University Hospital Clinical Research and Medical Innovation Center, Division of Biostatistics, Sapporo, Japan, 11Tsuyama Chuo Hospital / Shizuoka Cancer Center, Aizawa Hospital / Sapporo Teishinkai Hospital, & PROTON-NET Group, Japan

Purpose: To evaluate the basic data quality of PROTON-NET as a potential international source for establishing clinical evidence.

Materials and Methods: A national consensus was reached for the selection criteria, treatment protocols, and patient follow-up intervals with proton beam therapy (PBT) in 91 situations for 40 diseases at 9 tumor sites in 2015. A prospective data collection IT system has been developed and used for 2 years to collect a minimal clinical dataset. To receive reimbursement from the health insurance organization, all PBT institutions in our country must have fulfilled minimal requirements including use of the same selection criteria of patients, to enable discussion in the institutional cancer board which consists of surgical, medical, and radiation oncologists, to use the same treatment protocols, and to register all adult patients into the IT system. Data management was performed by an academic data center. Central monitoring using IT and on-site face-to-face monitoring was conducted at all institutions by an academic society.

Results: The central and on-site monitoring have shown that all institutions fulfilled the minimal requirements. There were 4,842 PBT patients registered from the 14 institutions between 2016 May 1st and 2018 June 30th. Excluding patients with prostate cancer, the local control rate, progression-free, and overall survival at 12 months was 90.1%, 60.7%, and 95.5% respectively. Grade 3, 4, and 5 late toxicity (CTCAE ver.4.03) was observed in 38 (1.6%), 3(0.1%), and 2(0.1%) patients respectively.

Conclusions: The quality of PROTON-NET was shown to be reliable as a basis for establishing clinical evidence.


Exploring the potential of a fixed proton beamline fully integrated into a conventional treatment room for photon therapy

S. Fabiano1, M. Bangert2, M. Guckenberger1, J. Unkelbach1

1University Hospital Zürich, Department of Radiation Oncology, Zurich, Switzerland, 2German Cancer Research Center, Department of Medical Physics in Radiation Oncology, Heidelberg, Germany

Purpose: Proton Therapy (PT) is a limited resource that is not available to all patients who may benefit from it. We explore the potential of a new cost-effective design for PT, which may facilitate proton treatments in conventional treatment rooms and allow the widespread use of protons.

Material and Methods: We consider the following design: The treatment room consists of a standard Linac for IMRT, a motorized treatment couch to treat the patient in lying position, and a horizontal proton beamline equipped with pencil beam scanning. With this setup, proton plans may be sub-optimal as beam angles are limited to a coronal plane. However, high-quality treatment plans may be realized by delivering protons and photons in the same fraction. Treatment planning is performed by simultaneously optimizing IMRT and IMPT plans based on their cumulative physical dose. We demonstrate this concept for a head and neck cancer.

Results: Figure 1 illustrates the proton and photon dose contributions in an optimal combination and their cumulative dose. Figure 2a compares the DVHs for the proton and photon dose contributions. Photons are used to improve dose conformity while protons allow reducing the integral dose to normal tissues. In fact, the combined treatment improves on both single-modality IMRT and IMPT plans (Figure 2b) and achieves 74% of integral dose reduction in normal tissues that the IMPT plan yields.

Conclusions: Affordable PT systems will likely include a fixed beamline rather than a gantry. Proton-photon combinations may retain high treatment quality while making protons available to more patients.


Creation of proton minibeams using single quadrupole Halbach cylinders

G. Mcauley1, A. Teran1, J. Slater1, A. Wroe1

1Loma Linda University, Radiation Medicine, Loma Linda, CA, USA

Proton minibeam radiation therapy (pMBRT) allows normal tissue sparing by utilizing an array of beamlets to deliver a spatially fractionated proximal dose that blends into a homogeneous dose at the target. These elliptical beamlets have very narrow lateral dimensions (<= 1.0mm) typically produced using precision collimators or MLC's. However, the use of these beam shaping devices can negatively impact dose rate and lead to the production of extraneous secondary particles. In the present work we investigated the potential of using a single magnetic quadrupole to produce the planar proton minibeams used by pMBRT. Monte Carlo simulations of unmodulated pencil beams with a 10mm initial diameter and 9.8cm range in water were focused with a single magnet of length 8.0cm and a field gradient of 250T/m. The combined dose distribution from five beamlets with center to center separation of 5.5mm and lateral FWHM of 1.2mm at 1.0cm depth showed high proximal spatial fractionation. The peak-to-valley dose ranged from 27.2 to 1.0 over 60% of particle range, and Bragg peak-to-entrance dose ratios for peaks and valleys were 19.2 and 0.73, respectively. At the level of the Bragg peak, the lateral beam dimensions were 2.7 and 2.6cm FWHM (Figures 1 and 2). This preliminary data suggests that magnetic focusing in pMBRT can deliver dose distributions that are comparable and potentially superior to those generated using collimators or MLC's. Magnetic focusing technology for pMBRT can be applied both in passive and active proton delivery and is the subject of ongoing research.


Towards magnetically focused proton minibeams: Investigating the limits of a clinical PBS nozzle

T. Schneider1, L. De Marzi2, A. Patriarca2, Y. Prezado1

1Imagerie et Modélisation en Neurobiologie et Cancérologie IMNC, CNRS - Université Paris 11 - Université Paris 7, Orsay, France, 2Institut Curie - PSL Research University, Center de Protonthérapie d'Orsay - Radiation Oncology Department, Paris, France

Purpose: Proton minibeam radiation therapy [1] seeks to promote normal tissue sparing through spatial fractionation of the dose, thereby widening the therapeutic window [2,3]. To maximise this effect, the beam width should be below 3 mm (FWHM) [2,6]. Currently, minibeams are generated using a multi-slit collimator [4,5], however, magnetic focusing will be necessary to increase dose rates, reduce neutron production and enable 3D intensity modulation. Towards this goal, a feasibility study based on a clinical PBS nozzle was conducted.

Methods: The Monte Carlo simulation toolkit TOPAS v.3.1.p02 [7] was used to model a complete PBS nozzle including the quadrupole and dipole magnets. The magnetic fields were varied and several geometry modifications were investigated to assess the focusing limits.

Results: Focusing limits of the current configuration were established: 12.3 mm at 100 MeV and 6.4 mm at 200 MeV. The beam size may be reduced considerably by adding quadrupole magnets (1.8 mm at 100 MeV, 1.4 mm at 200 MeV) or considering a more compact nozzle (1.1 mm at 100 MeV, 0.6 mm at 200 MeV).

Conclusion: It will be challenging to realise collimator-free generation of proton minibeams at current clinical beamlines. However, different approaches to obtain the required beam size are proposed.

References: [1] Prezado et al., Med. Phys., 2013. [2] Prezado et al., Scie. Reports, 2017. [3] Prezado et al., Radiat. and Oncology, 2018. [4] Peucelle et al., Med. Phys., 2015. [5] De Marzi et al., Med. Phys., 2018. [6] Prezado et al., submitted to Int. J. Radiat. Oncol. Biol. Phys. [7] Perl et al., Med. Phys., 2012.

General: New Investigator


Radiographer led daily cone beam CT anatomical match and online correction for adult tumor sites treated with proton beam therapy

C. Boon1, P. Aka2, I. Boon3, J. Clorley2, J. Lambert2, K. Leaver2, K. Owen2, J. Pettingell2, T. Oliver2, A. Warlow2

1Clatterbridge Cancer Center, Oncology, Birkenhead, United Kingdom, 2Rutherford Cancer Center South Wales, Clinical Oncology, Newport Wales, United Kingdom, 3Leeds Cancer Center, Clinical Oncology, Leeds, United Kingdom

Background: In UK radiotherapy centers, radiographer-led or radiographer alone daily cone-beam CT (CBCT) matches is the standard of care. In the first UK Proton Beam Therapy center treating non-paediatric cancers, the concept of radiographer alone daily CBCT and ‘on-line' correction has been implemented.

We compared the ‘on-line' daily cone-beam CT matches and shifts performed by radiographers during clinical treatments with ‘off-line' reviews carried out by oncologists.

Methods and Results: Our center is equipped with IBA Proteus®ONE proton therapy machine incorporating large field of view kV CBCT and 6D robotic table.

Every patient undergoes daily CBCT imaging with on-line matching to planning CT and 6D patient position correction carried out by treatment radiographers using IBA's adaPT Insight® software.

We reviewed daily matches and corrections made by radiographers with ‘off-line' reviews by oncologists to:

  1. Compare radiographer matches with those made by oncologists to determine the magnitude and range of changes (if any),

  2. Adequacy of image quality to determine anatomical matches,

  3. Anatomical changes that would prevent daily proton beam delivery or require re-planning.

Data will be presented from the first 15 non-paediatric cancer patients treated on Proteus®ONE in our center since commencing treatments in April 2018.


Survival and radiation damage analysis of human skeletal muscle cells after photon/ion irradiation: Experimental data and Monte Carlo simulations

A. Cicchetti1, F. Ballarini2, T. Rancati3, M. Carrara4, N. Zaffaroni5, R. El Bezawy5, M. Carante2, A. Facoetti6, M. Ciocca6, R. Valdagni7

1Università di Pavia, Physics, Milan, Italy, 2National Institute of Nuclear Physics INFN, INFN-Sezione di Pavia, Pavia, Italy, 3Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program, Milan, Italy, 4Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Physics, Milan, Italy, 5Fondazione IRCCS Istituto Nazionale dei Tumori, Experimental Oncology and Molecular Medicine, Milan, Italy, 6Fondazione CNAO, na, Pavia, Italy, 7Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program & Radiation Oncology 1, Milan, Italy

Skeletal muscles were rarely included in the studies of dose-response relationship of normal tissues after radiation therapy (RT), even if they surround the tumor location in many cases and their damage could lead to worsening of complex functional endpoints (e.g. urinary symptoms, fecal continence, sexual dysfunction, dysphagia).

Recently, our group used texture analysis of T1&T2-weighted images to investigate RT-induced changes in the pelvic obturator muscles (Scalco Med Phys 2018). A clear exponential relationship between mean signal intensity and local RT dose was found, thus supporting the hypothesis that imaging can be used to objectively determine muscle insult induced by RT.

This new project, funded by the National Cancer Institute in Milan, aims at investigating the radiation response of human skeletal muscle cells (HSkMCs purchased from commercial vendors, never used in this context so far), both by in vitro experiments on cell DNA-damage and cell survival, and by Monte Carlo simulation.

Specifically, we will determine the radiobiological parameters of HSkMC upon irradiation with photon and proton/carbon ion beams at several dose points. Cell survival data will be compared with the outcomes of a simulation code modified ad hoc to deal with HSkMCs (Ballarini and Carante Radiat Phys Chem 2016). A second set of experimental measurements will include kinetics of γ-H2AX foci and apoptosis detection; this will provide further information to be included in the code.

Because the number of patients treated with hadrons is still limited, we can expect that radiobiological understanding of muscle response could help to identify constraints for hadron treatment planning.


The project NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy UNraVeled)

G. Cuttone1, S. Agosteo2, A. Attili3, P. Cirrone1, V. Conte4, R. Faccini5, G.I. Forte6, C. La Tessa7, L. Manti8, G. Petringa1, P.A. Lojacono1

1Istituto Nazionale di Fisica Nucleare INFN, Laboratori Nazionali del Sud LNS, Catania, Italy, 2Istituto Nazionale di Fisica Nucleare INFN, Sezione di Milano, Catania, Italy, 3Istituto Nazionale di Fisica Nucleare INFN, Sezione di Roma3, Catania, Italy, 4Istituto Nazionale di Fisica Nucleare INFN, Laboratori Nazionali di Legnaro, Catania, Italy, 5Istituto Nazionale di Fisica Nucleare INFN, Sezione di Roma1, Catania, Italy, 6National Research Council, Institute of Molecular Bioimaging and Physiology, Cefalù, Italy, 7Istituto Nazionale di Fisica Nucleare INFN, Trento Institute for Fundamental and Applied Physics, Catania, Italy, 8Istituto Nazionale di Fisica Nucleare INFN, Sezione di Napoli, Catania, Italy

Recently an increase of proton therapy effectiveness for irradiations occurring in the presence of 11B atoms has been observed. A role in this effect should be played by the high-LET alpha particles mainly generated by the p(11B,a)2a channel, which has a cross section of the order of 1 barn at very low incident proton energy. However, analytical calculations indicate that the number of alphas produced is too low to yield the observed biological effects.

The Italian INFN institute recently funded a project called NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy UNraVeled) with the main aim to study and understand this radiobiological effect.

The main objectives of NEPTUNE will be the consolidation of these results, extending them to include another nuclear reaction between protons and 19F and focusing on understanding all the physical and biological mechanisms involved. A physical characterization of the radiation field will be performed with tissue-equivalent detectors of various types, all based on micro- and nanodosimetric techniques. At the same time, biological measurements will be performed for different cell lines using several endpoints. New biological approaches will be to considered to study the problem from different points of view, which could reveal mechanisms not yet considered. All experimental data will be compared with predictions from analytical and Monte Carlo models.

The project is divided into four main Working Packages: WP1, modelling; WP2: imaging and quantification; WP3: microdosimetry and WP4: radiobiology. An additional group (WP5) coordinates all the foreseen experimental activities.


Quantifying DNA damage in comet assay images using neural networks

S. Dhinsey1, T. Greenshaw1, J. Parsons2, C. Welsch1

1University of Liverpool, Department of Physics, Liverpool, United Kingdom, 2University of Liverpool, Institute of Translational Medicine, Liverpool, United Kingdom

Proton therapy for cancer treatment is a rapidly growing field as increasing evidence suggests it induces more complex damage in DNA than photons. Accurate comparison between the two requires quantification of the damage caused, one method being the comet assay. The program discussed here, based on neural network architecture, aims to speed up analysis of comet assay images and provide accurate assessment of the DNA damage levels apparent in them.

The comet assay is an established technique in which DNA strand breaks are spread out, creating a comet-like object, Figure 1. The elongation and intensity of the comet tail indicate the level of damage incurred. Many methods to measure damage exist, from “by eye” ranking systems to computer software, which can be time consuming. They result in analyzing only a small fraction of images, which is a problem addressed by this program.

The neural network performs object detection and localization using instance segmentation (Figure 2). Rather than extracting features to distinguish if and where an object is, instance segmentation incorporates the bounding-box method with pixel-wise classification, aiming to sort pixels into one of three classes: comet, background or contamination. The purpose is to provide accurate measurements of the comet tail length and tail DNA fraction, some common features used to measure DNA damage following a comet assay. Further, modelling of the comet assay process is underway to provide a better understanding of the relationship between the assay images and the underlying level of DNA damage.


Implementation status of carbon ion beam therapy at MedAustron

M. Stock1, P. Fossati2, L. Grevillot1, G. Kragl1, A. Carlino1, G. Martino1, P. Georg2, E. Hug2

1EBG MedAustron GmbH, Medical Physics, Wiener Neustadt, Austria, 2EBG MedAustron GmbH, Radiation Oncology, Wiener Neustadt, Austria

MedAustron is a synchrotron based dual particle therapy facility, which started proton therapy in December 2016. Till end of 2018, 293 patients were successfully treated in 2 treatment rooms using fixed-beam lines. Early 2019, technical commissioning of a horizontal beam line for carbon ions has been completed, and medical commissioning is ongoing.

In July 2019, carbon ion radiotherapy (CIRT) treatments will start. Main beam properties are: 242 energies from 120-402.8MeV/n (ranges in water from 2.9cm-27cm in 1mm steps – Figure 1), spot sizes (in FWHM at isocenter in air) from 6mm (402.8MeV/n) to 10mm (120MeV/n) and maximum field size of 20x20cm2.

The patient positioning system is designed for non-isocentric setups, allowing treatments close to the nozzle and reducing uncertainties in dose calculation with range shifter mounted in the fixed nozzle and pencil beam algorithms (Figure 2). RayStation8B (partly developed based on MedAustron requirements) will be commissioned for CIRT planning based on LEM I as RBE model.

In the first two years established Japanese protocols will be followed. A hypo-fractionated schedule (16 fractions) will be used for H&N non-SCC cancer, sarcoma and local recurrence from rectal cancer. Dose will be adapted after correction for RBE models. With the availability of motion management, hypo-fractionated CIRT will later be used in pancreatic cancer patients with 12 fractions for locally advanced cancer LAPC and 8 fractions for preoperative treatment. HCC will be treated with 2 fractions only. Spine and skull base chordoma will be treated with 3 GyRBE per fraction according to German protocols.

General: New Investigator Poster Discussion Sessions


New designs of electrostatic lens systems with quadrupole multiplets for production of sub-micron ion beam

H. Arya1, V.A. Chirayath1, M. Jin1, A.H. Weiss1, G.A. Glass2, Y. Chi1

1University of Texas at Arlington, Physics Department, Arlington, TX, USA, 2University of North Texas, Physics Department, Denton, TX, USA

We have initiated an inter-university effort for the reconstruction of a new sub-micron ion beam to unravel the far-from-solved fundamental mechanisms in the ion-induced-damage of cellular matrix involved in heavy ion therapy. To obtain a sub-micron beam at the Gaussian image plane with a 30μm object aperture, we have designed two electrostatic lens systems and compared their performance with that of the electrostatic quadrupole sextuplet (EQS) currently employed at the micro ion beam facility in Columbia University1.The design and simulations were done using SIMION 8.1® and GICOSY with both software benchmarked by accurately reproducing the experimentally measured parameters of the EQS. With an emittance of 0.2μm-mrad at the object aperture for 3MeV/q ion beams, our designed electrostatic quadrupole triplet (EQT) is capable of providing a high demagnification of (Df) of 89.4 at a working distance (Dw) of 170mm, while the designed electrostatic quadrupole quadruplet (EQQ) gives a Df of 32.5 at a Dw of 98mm. In comparison, the Columbia EQS1 lens system has a Df ∼ 38 at a Dw of 126 mm under the same input conditions. The physical lengths of EQT, EQQ and EQS are 0.835m, 0.850m and 3.887m, respectively. Apparently, the EQT achieves a higher demagnification with a more compact lens design and fewer quadrupoles. Our study also shows that with beam distortions at the image plane due to spherical aberrations (for divergence upto 0.03 mrad) and chromatic aberrations (δE/E upto 3.0E-4), EQT still produces a sub-micron beam at the target, indicating its stable performance.


Robustness metrics for two different beam arrangements in IMPT for nasopharyngeal cancer

L.P. Kaplan1, R.A. Perez1, A. Vestergaard2, S.S. Korreman1

1Aarhus University Hospital, Department of Oncology, Aarhus N, Denmark, 2Aarhus University Hospital, Danish Center for Particle Therapy, Aarhus N, Denmark

Aim: We analyze robustness of two IMPT beam arrangements towards rigid shifts and range uncertainties using robustness metrics. A “standard” three-beam arrangement is compared to a five-beam split-field technique which will be standard practice at our coming proton therapy facility.

Methods: Two robustly optimized IMPT plans (68/60/50Gy SIB) were generated using Eclipse (v13.7) for five nasopharyngeal cancer patients: three fields (two anterior-oblique, one posterior) or five fields with split targets (one anterior, two anterior-oblique, two posterior-oblique delivering dose only ipsilaterally; fig.1). Robust optimization parameters for target volumes, upper pharyngeal constrictor, and contralateral parotid were ±4mm shifts along cardinal axes and ±3% range errors for both plan types. Two robustness metrics were calculated: area spanned by error-scenario DVHs (ADVH), and best-to-worst-case difference (DiffBW) of relevant DVH metrics. For both, smaller values indicate higher robustness.

Results: Mean ADVH for all targets was 27.6%, 25.3%, and 30.9% smaller for 3-field plans than for 5-fields (fig.2), and mean DiffBW of dose covering 99% (high-risk) or 98% (intermediate/low-risk) differed <0.1Gy between plan types. For brainstem and pharyngeal constrictor levels, mean ADVH was smaller for 3-fields than for 5-fields (3.5% and 35.3/21.3/8.5%). For spinal cord and both parotids, mean ADVH was 38.8% and 6.3/4.2% larger for 3-fields. For brainstem and spinal cord, mean DiffBWf or dose to the hottest 1cc (D1cc) was 14.7/15.8Gy and 14.1/13.7Gy for 3-fields/5-fields.

Conclusion: Minimum target coverage is equally robust toward shifts and range errors in both plan types, but for higher doses 3-fields are more robust. For OAR, ADVH differences indicate robustness varies for different anatomical regions.


Implementation of an internship program as a new clinical methodology and practice

E. Gittings1, J. Stamper1

1Provision Proton Cancer Center, Dosimetry, Knoxville, TN, USA

The standard progression into dosimetry begins as a radiation therapist. Individuals make a natural transition into dosimetry where enrolling in an educational program and taking the MDCB exam were both optional in the United States. Three years ago, completing a dosimetry program to sit for the MDCB became a requirement, essentially removing the option for on-the-job training and self-learning. With this change, the option for many therapists to segue into dosimetry was eliminated based on the location of many of the educational institutions as well as the financial aspect related to the decision of shifting careers. A reduction in potential talent with an established background in an already small field, is an unintended byproduct of changes that are meant to raise standards. In order to foster continued education and development for current radiation therapists, an adoption of new methodologies is recommended to facilities. This new methodology would include creation of an internship program at facilities that are open to current radiation therapists. An internship program would not only benefit the radiation therapist looking to become a dosimetrist, but also the facility as a future investment. In particular to proton therapy, where planning techniques are different than photons and education on this topic in schools is very limited, an internship program would provide an invaluable bridge between therapy and dosimetry roles. The scope of this will include personal experience as an intern myself, as well as provide comparative data on online dosimetry programs with outcomes to brick and mortar institutions.

Physics: Beam Delivery and Nozzle Design


Study of treatment duration as a function of machine parameters for a proton pencil beam scanning synchrotron with multi-energy-extraction

C. Beltran1, P. Mark1, K. Furutani1

1Mayo Clinic, Radiation Oncology, Rochester, MN, USA

Mayo Clinic Rochester switched to treating with MEE in January 2018. The significant reduction in treatment duration due to MEE has been previously reported. There are several additional factors in synchrotron PBS which contribute to the irradiation time of a treatment field. They are: time to calculate delivered spot characteristics before delivering the subsequent spot (SCT); scanning magnet (SCM) speed; extracted beam current; charge in synchrotron; recapture efficiency between MEE energies; and time to switch MEE energies. To shorten the contribution to the irradiation time from each of these parameters would require modifications to the existing machine. To understand the significance of each parameter the recently published 4D dose calculator (Ref 1) was used to study the contribution of each of these parameters for two patients: a liver patient using repaint (RL) and a typical head and neck (HN) patient. For both patients reducing the spot calculation time has the greatest impact. The irradiation time is cut in half if SCT could be reduced to practically zero. Doubling the SCM Speed would reduce the irradiation time by about 10%. Doubling the beam current reduces HN by 15% and RL by 7%. Increasing the recapture efficiency from 50% to 99% reduced the irradiation time for HN by 9% and for RL by 12%. The impact of the combination of each of these parameters as well as the impact of the stored charge and time between MEE energies will be reported. 1) Pepin et al, Med Phys 45, (2018) pg. 5293.


A multi-cuboid ridge filter for optimized proton pencil beam delivery

A. Wroe1, A. Teran1, G. McAuley1, J. Slater1

1Loma Linda University, Radiation Medicine, Loma Linda, CA, USA

The purpose of this work was to design and optimize a multi-cuboid proton ridge filter (MCPRF) that can be used to increase the Bragg peak width in pencil beam scanning (PBS) treatments. Monte Carlo computer simulations were performed with the capability to insert or remove the MCPRF (Figure 1) and adjust device parameters including bar width (BW), bar spacing (BS), and filter thickness (FT).

Pencil beams of five monoenergetic proton energies (R50 of 51–103mm in water) were simulated and dose was recorded within a water phantom containing 0.25mm3 voxels. Benchmark simulations were completed without the MCPRF in place to determine the PBS depth dose profiles and establish baseline full-width at 80% maximum (FW80M) values. From these simulations the relative Bragg peak weightings and FT could be determined theoretically and optimal parameters for the MCPRF were established. In subsequent MCPRF simulations, depth dose profiles were analyzed to quantify the impact of the MCPRF with varying design parameters on the Bragg peak FW80M. Lateral and 2D dose profiles were compared to those without the MCPRF to ascertain any unintended impact to spot size, spot shape or range uniformity. Results for 80–118MeV indicate that the MCPRF was effective at increasing the Bragg peak FW80M as compared to the baseline from 16-78% (Figure 2) without impacting beam spot quality.

The results presented here suggest that the MCPRF is an effective two-step range modulator for PBS applications that may be useful in minimizing PBS treatments times and improving beam delivery efficiency, especially for shallow targets.


Development and testing of a preclinical cone for magnetically focused proton radiosurgery

G. Mcauley1, A. Teran1, J. Slater1, A. Wroe1

1Loma Linda University, Radiation Medicine, Loma Linda, CA, USA

High energy protons demonstrate beneficial dose deposition characteristics when treating small cancerous lesions including a low entrance dose, high dose Bragg peak and a well-defined range which limits integral dose. However, as beam diameter decreases below 1.0cm, beam broadening due to multiple Coulomb scattering (MCS) results in Bragg peak degradation that works against these advantages. Recent work in our laboratory suggests that magnetically focusing the proton beam immediately upstream from the patient could help compensate for the effects of MCS, potentially improving dose conformity and dose delivery efficiency for radiosurgical treatments. The purpose of the current project is to incorporate this technology into a pre-clinical beam delivery system for evaluation and testing at our facility. Similar to our bench-top design (Fig 1), the proposed cone (Fig 2) incorporates a triplet of quadrupole Halbach cylinders constructed from rare earth, radiation-hard Sm2Co17 permanent magnetic material with 10mm bore diameters and magnetic field gradients of 250T/m. The cone is optimized for dose delivery to small head lesions and has a form factor that mimics the stereotactic radiosurgery cone in use at our institution. Cone design and manufacture is currently ongoing and the latest results along with dosimetric evaluations will be presented. The use of the magnetically focusing cone as a drop-in replacement for a standard radiosurgery cone is expected to provide a simple and robust avenue to reduce entrance dose and beam number while delivering dose to millimeter-sized radiosurgery targets in less time than unfocused collimated beams.


Method for improved accuracy and speed from spot scanning systems

J. Gordon1, P. Boisseau1, A. Dart1, W. Nett2, S. Kollipara3

1Pyramid Technical Consultants Inc., Engineering, Lexington, MA, USA, 2Pyramid Technical Consultants Inc., Controls, Lexington, MA, USA, 3Pyramid Technical Consultants Inc., Proton Therapy Controls, Lexington, MA, USA

Pencil beam spot scanning magnets, whether combined X-Y or separate, typically use laminated iron-yokes energized by four-quadrant power supplies. Practical limitations such as magnet yoke hysteresis, eddy currents and power supply bandwidth affect the spot positioning accuracy, stability, reproducibility and speed. This is turn can affect dose conformity and treatment times.

Adding a small correction X-Y magnet with deliberately small bending power (a few mm shift at full energy) but high speed, placed before the main scan magnets, produces a hybrid scan system with more nearly ideal behavior. The magnet is distinguished from a conventional beamline steerer by having very low inductance and use of features like ferrite return yoke and single layer high current coils. Its control is tightly linked to the scan magnet control. The deflection of the combined system is the sum of the main magnet and correction magnet to very good approximation.

Using the correction magnet and feedback from main scan magnet fields or measured spot positions as necessary allows the following to be performed in real-time:

  • correction of small position errors caused by hysteresis

  • compensation of small drifts in position due to eddy current decay, beam trajectory change or power supply instability

  • faster settling of position by compensating over or undershoot of the main field

  • deliberate blurring of a beam spot to increase its effective size and thus reduce the number of spots needed


Novel beamline diagnostics for proton beam facilities

M. Grossmann1, O. Actis2, W. Diete3,4, D. Rudolf5, H.U. Klein3,4, R. Kramert6, D. Meer2, C. Venkataraman4, T. Waterstradt4, D.C. Weber2

1Paul Scherrer Institute, Center for Protontherapy, Villigen PSI, Switzerland, 2Paul Scherrer Institut, Center for Protontherapy, Villigen PSI, Switzerland, 3Advanced Accelerator Technologies, Advanced Accelerator Technologies, Villigen, Switzerland, 4Axilon AG, Axilon AG, Koeln, Germany, 5Paul Scherrer Institut, Large Research Facilities, Villigen PSI, Switzerland, 6Dipl.-Ing. Kramert GmbH, Dipl.-Ing. Kramert GmbH, Remigen, Switzerland

Beam diagnostic elements have been designed by PSI and continuously improved ever since the start of the PROSCAN proton therapy facility in 2007. In 2018, a Swiss company (AAT) developed new monitors based on the original PSI detectors, incorporating experience gained from many years of PROSCAN operation. State-of-the-art instrumentation development and engineering helped to optimize performance and control system compatibility.

The Profile Monitor is a retractable multi-strip ionization chamber (MSIC). It consists of a stack of specially patterned, metalized ceramic plates in a box filled with ambient air. Profiles are measured in both orthogonal planes (x/y) with a resolution of 1 mm in the central area and a lower resolution of 2 mm in the outer beam areas.

The Current Monitor is an ion chamber formed of a stack of five 5μm Ti foils. The outer and the central foils are connected to the HV supply. The other two foils deliver two independent and redundant current signals.

The CoM/Halo Monitor is an open bore ion chamber set-up with segmented pick-up rings. It provides a continuous monitoring of the beam centering.

A new multi-channel wide-gain pico to micro current amplifier has been developed to acquire data from the three detector types. It can be used with a standalone LabView application for testing and via a USB and Ethernet (TCP/IP) for beamline controls integration.

Tests have been performed with PSI's therapeutic proton beams with currents ranging 0.0…1.0 nA and energies ranging 70 … 230 MeV.


A new treatment control system for a low energy proton therapy fixed beam line

P. Hofverberg1, J. Hérault1, G. Angellier1, J.M. Bergerot1

1Center Antoine Lacassagne, Department of radiation therapy, Nice, France

MEDICYC is a 65 MeV isochronous cyclotron at Center Antoine Lacassagne (CAL) in Nice, France dedicated to treating ocular tumors using proton therapy. Treatments are delivered by means of a fixed beam line and single passive scattering. MEDICYC performs on average 1200 treatment fractions per year, and consistently achieves treatment durations as low as 10 s, and distal and lateral penumbrae of 0.6 and 1.4 mm tissue equivalent respectively.

A new treatment control system is being developed for MEDICYC to perform treatment planning, treatment delivery and beam quality assurance. The system complements the existing TPS EyePlan with functionalities such as dose/MU calibration, dose rate calculations and design of beam modulating accessories. It also provides the full functionality needed to safely deliver and monitor a treatment, including a record and verify system to organize and upload patient data to the delivery machine. Delivered dose is measured using a two-channel setup, and with an independent method based on the quantity of secondary radiation recorded during a treatment, developed in-house. Finally, hardware and software tools are provided to conduct the daily beam quality assurance and to analyze the results with respect to historical data.

In this presentation, the hardware and software design choices that were made to meet the objectives described above while meeting stringent criteria with respect to safety, treatment delivery accuracy and treatment efficiency and beam availability, are discussed.


Implementation of chair in fixed carbon-ion beamline to treat head/neck cancer at seating position: I. hexapod 6-axis parallel positioner

W.C. Hsi1, R. Zhou2, X. Zhang2, F. Yang2, Z. Wang2, S. Yinxiangzi3, J. Sun3

1University Florida Health Proton Therapy Institute, Radiation Oncology, Jacksonville, USA, 2Sichuan University, College of Physical Science and Technology, Chengdu- Sichuan Province, China, 3Shanghai Proton and Heavy Ion Center, Department of Medical Physics, Shanghai, China

Multiple fixed-beamline carbon-ion fields in patient's sagittal plane provided clinical acceptable target doses with carbon-ion high dose-gradient and enhanced radiobiological effectiveness. However, non-planar fields with a 20-degree title angle to patient's transverse plane could achieve better dose-sparing of organs-at-risk. To have non-coplanar fields, a non-gantry solution by utilizing isocentric rotating chair as a patient positioner can be equivalently to a heavy/expensive gantry solution; having large 60-degrees title angle but is rarely used in actual treatments. Two distinctive conceptual approaches; referred as parallel (PM) and series mechanism (SM), were used to manufacture a positioner. The advantages and pitfalls using either PM or SM approach for a seating positioner was evaluated under the realistic constraints in our fixed particle beamline as shown in Fig 1. A robot system based on SM approach was found an interference occurring between robot arm and patient's leg rest. Based on PM approach, a compact Stewart Hexapod platform allows +/- 20-degree title but its translation displacement was highly reduced. By adding 3D translation and 360 rotation modules, combined Hexapod system can full perform the displacements over a 500 mm cubic treatment volume with 20-degree tilt and 360-degree rotation as shown in Fig. 2. For each subunit, its elastic deformation was simulation and its mechanical accuracy was evaluated by a laser-based tracking system. The validation of positioning accuracy for fully assembled chair was conducted to placing a head phantom at clinical treatment condition. An accuracy of ±0.8mm and ±0.6 degrees over 500mm treatment volume was achieved.


Study of optimizing treatment delivery with an add-on mini-ridge filter for synchrotron-based proton beam scanning system

X. Li1, C. Zhiling2, P. Yuehu2, G. Mengya3, K. Haiyun3, L. Qi3, Z. Zhentang2

1Shanghai APACTRON Particle Equipment Co.- Ltd, research and development department, Shanghai, China, 2Shanghai Advanced Research Institute, Shanghai Synchrotron Radiation Facility, Shanghai, China, 3Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China

Aim: A synchrotron-based proton therapy system in the Shanghai Ruijin Hospital Proton Center is currently under beam commissioning. It consists of two pencil beam scanning treatment rooms (1 horizontal beam and 1 half-rotating gantry), one eye treatment room and one experimental room. To reduce the number of energies to generate a smooth SOBP while minimizing the impact of plan qualities, the design of an add-in mini-ridge filter (MRF) has been studied on the dose uniformity in the SOBP and beam delivery efficiency.

Methods: To reduce the total treatment time for large volumes or motion mitigation, different design of add-on MRF has been simulated in TOPAS. Using these simulations, Monte Carlo data were generated for TPS commissioning. For each design, dose uniformity, lateral and distal penumbras in water phantom or clinical case for shallow and deep target with and without MRF will be compared. Beam delivery time will be analyzed.

Results and Conclusions: For synchrotron-based proton beam scanning system, the use of an add-on MRF is significantly beneficial to reduce the number of energies to obtain a smooth SOBP and shorten treatment times for some cases. But the design and choice of MRF is important to balance treatment time and normal tissue dose.

References: 1. Weber U and Kraft G 1999 Design and construction of a ripple filter for a smoothed depth dose distribution in conformal particle therapy Phys. Med. Biol. 44 2765–752. 2. Perl J, Shin J, Schumann J. TOPAS: an innovative proton Monte Carlo platform for research and clinical applications. Med Phys. 2012 Nov; 39:6818-37.


Dosimetric evaluation of range shifter designs based on beam data generated from GEANT4 code

Y.H. Lin1, H.Q. Tan1, L.K.R. Tan1, K.W. Ang1, J.C.L. Lee1, S.Y. Park1

1National Cancer Center Singapore, Department of Radiation Oncology, Singapore, Singapore

Range shifter is used in pencil beam proton therapy for treating shallow targets. It degrades the beam energy by shifting the spread-out Bragg peak close to the patient's surface. Our upcoming proton therapy system produces a nominal minimum energy beam of 71.3 MeV, which corresponds to a range of 4 cm in water equivalent thickness. In this work, Monte Carlo simulation with the GEANT4 code is used to simulate the beam data with three different thickness of range shifters for an asymmetry field size scanning range. The beam data of different proton energies are simulated in (i) voxel water phantom of 0.1 mm resolution to generating the integrated depth dose, and (ii) voxel air phantom of 0.2 mm resolution to calculate the beam spot size at isocenter. The beam data is input into Eclipse Treatment Planning System (version 13.7), to further evaluate the dosimetric impacts on a few clinical cases. Parameters such as homogeneity index and conformity index are used for quantifying the dosimetric differences of using these three range shifters. Since accurate modelling of range shifter allows us to calculate the beam spot size entering the patient, we would have better understanding of the implementation of range shifter in our pencil beam scanning system and avoid any potential pitfalls that may arise from our own design of range shifter. We foresee this work to be helpful for other upcoming proton centers that would use a similar system.


Study of parameters and errors affecting performance of synchrotron-based proton beam scanning system

G. Mengya1, L. Xiufang2, K. Haiyun1, L. Qi1, P. Yuehu2, C. Zhiling3, Z. Zhentang3

1Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China, 2Research and Development, Shanghai APACTRON Particle Equipment Co-Ltd, Shanghai, China, 3Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China

Aim: To optimize the overall performance of a Synchrotron-based Proton Beam Scanning System (SPBSS) during the commissioning, spot scanning parameters and errors in beam delivery has been studied extensively.

Methods: A synchrotron-based proton therapy system (Shanghai Advanced Proton Therapy project, SAPT) is currently under beam commissioning. A SPBSS simulation platform has been developed to calculate resulting dose distribution in water phantom or patient cases, as well as beam delivery time for specified parameters. Major parameters variations may cause dose error, including spot position error, beam size variation due to slow extraction spill characters and spot weight errors. Based on the GEANT4 Monte Carlo calculations and beam measurements data, a set of data libraries and parameters, which represent the various combination of major performance or error contributors, has been determined and used as base data for the treatment planning system-matRad1 and SPBSS simulation. Their individual and combined effect against treatment planning spot configuration and optimization method on the dose distribution is quantified.

Results: The configuration of SPBSS and treatment planning parameters are trade-offs between the system reliability, treatment efficiency and plan quality. Comprehensive relations between selected parameters are visualized with plots.

Conclusions: To speed up the commissioning as well as provide a baseline for machine tuning, the relation between those TPS parameters, imperfections of beam delivery system and resulting dose errors has been studied to find optimal configuration sets for performance optimization of representative treatments.


Analysis of treatment planning statistics for the first Mevion HYPERSCAN proton therapy system

K. Milkowski1, D. Pang2, M. Jones1

1Mevion Medical Systems, Engineering, Littleton, MA, USA, 2MedStar Georgetown University Hospital, Radiation Oncology, Washington D.C., USA

Purpose: To analyze the first 9-months of system data from the first clinical HYPERSCAN (S250i) system to determine the extent of the treatment space being utilized.

Method: Anonymized DICOM Plans and Records for the first 9-months of treatment have been collected and analyzed for content. This includes investigating the number of treatment beams for each plan, as well as the typical energies and treatment angles most used by these beams. The plans were also inspected for whether or not they utilized the Adaptive Aperture.

Results and Conclusion: There were 156 beam fields analyzed spanning March to December of 2018. The typical treatment plan for the first S250i system contained 2 treatment fields (average 2.17) and all beams utilized the adaptive aperture for a sharper penumbra. The most common treatment angle was a 90-degree lateral, followed by 155-160 degree posterior obliques (see Fig 1). Despite the nominal 227MeV energy of the Mevion S250i system, the highest energy used in any treatment field was only 213MeV and in excess of 95% of beams were delivered entirely using energies of 200MeV or less (see Fig 2).

At the highest level, the treatment plans prescribed for the Mevion S250i system are quite similar to those most commonly employed by the original Mevion S250 scattering system in number of beams, treatment angles and energies used. Anonymized DICOM treatment plans and records can be a valuable tool for generating treatment statistics for making efficiency optimizations and future design considerations.


Response to ambient temperature of a dose monitor in particle beam therapy

M. Mizota1, Y. Tsunashima1, T. Himukai1, R. Ogata2, T. Uno2

1Ion Beam Therapy Center- SAGA HIMAT Foundation, Physics, Tosu, Japan, 2Accelerator Engineering Corporation, SAGA-HIMAT Office, Tosu, Japan

Background: For a vented ion chamber, the output varies depending on changes in both temperature and barometric pressure, so it is necessary to correct its output. The ambient temperature is adjusted to be constant using the air conditioner, but it may change somewhat depending on the operation state of the equipment used for the particle beam therapy. We confirmed whether the change in monitor output due to ambient temperature can be represented by well-known atmospheric correction coefficient.

Methods: Under certain irradiation conditions, the absorbed dose per dose monitor output (Gy/Count) can be obtained by a combination of a dose monitor (a vented ion chamber) located at the snout and a Farmer type ion chamber placed at the isocenter. The temperature of the location of the ion chamber of the Farmer type was kept almost constant, and the output (Gy/Count) was measured by changing the temperature near the dose monitor by operating the air conditioner. Regarding the temperature near the dose monitor, the sensor of thermometer was located in the place as close as possible.

Results: A considerable time delay was seen in the change in output of the dose monitor compared to the change in ambient temperature.

Conclusion: Chambers require time to reach thermal equilibrium with their surroundings. In a situation that the ambient temperature is changing, therefore, an appropriate correction should be necessary considering the time response determined from the positional relationship between the dose monitor and the thermometer in the irradiation equipment.


Design and test of an octupole scanning magnet for proton therapy

L. Ouyang1, B. Jia2, D. Li1

1Shanghai Institute of Applied Physics- Chinese Academy of Sciences, Power Supply, Shanghai, China, 2Shanghai Institute of Applied Physics, Power Supply Department, Shanghai, China

Proton beams have several features that make them very effective in radiation therapy applications. These include high dose localization as well as high biological effect around the Bragg peak. Moreover, magnetic scanning methods allow one to spread an ion beam to an exact image of a complex tumor shape. The ion scanning system usually consists of two magnets, each scanning horizontal and vertical directions independently. This paper discusses the design for a novel octupole magnet design that provides beam deflection over a dipole field which can be set up at any azimuthal angle in the volume of the magnet bore. A test of the static and dynamic performance of the octupole scanning magnet has been performed using Hall probes and coils to measure the field inside the magnet and the results are presented in this paper.


Managed Beam Service (MBS) provided by Muir PT: A novel way of delivering proton beams utilizing mechatronics

K. Paul1, F. Vernimmen2

1Cork University, Engineering, Cork, Ireland, 2Cork University Hospital, Radiation Oncology, Cork, Ireland

The current beam delivery system serving multiple treatment rooms has been a fixed accelerator (cyclotron/synchrotron) extracting a beam into a fixed beam line going to a number of adjacent treatment rooms, usually 3-4. Most treatment rooms have rotating 360-degree gantries for flexible beam delivery. The 360 degree These gantries are large, expensive and not only do the treatment rooms need radiation shielding but so also does the beam line itself. This current delivery system traditional approach has a substantial upfront capital strain and high ongoing operational cost.

Muir PT is offering the first Managed Beam Service (MBS) using a new mechatronics concept to re-engineer the proton therapy delivery system - with an 20% current system80% reduction in physical size even for the standard 6 room modular configuration. All equipment including shielding is factory assembled and delivered to hospital site pre-certified. Lead time from order to delivery is one year. Muir PT will make the Managed Beam Service (MBS) available to Healthcare Providers on a pay-per-treatment basis at the equivalent per treatment cost of Photon Therapy; that is, on a pay per treatment basis. This Managed Beam Service (MBS) delivers is assured outcomes in a manner that avoids upfront capital strain for the Healthcare Provider and covers the facility's operations and maintenance cost.


Shorter treatment time by intensity modulation with a betatron core extraction

M. Pullia1, S. Savazzi1, V. Lante1, S. Foglio1, M. Donetti1, L. Falbo1, L. Casalegno1

1CNAO, Technical Department, Pavia, Italy

The CNAO (National Center for Oncological Hadrontherapy) main accelerator is a synchrotron capable to accelerate carbon ions up to 400 MeV/u and protons up to 250 MeV. Three treatment rooms are available and are equipped with horizontal beam lines; one of the treatment rooms also features a vertical treatment line to allow additional treatment ports. All of the beamlines are equipped with a pencil beam scanning system for dose delivery. With such a dose distribution technique, particles are sent to different depths by changing the energy from the synchrotron and are moved transversally by means of two scanning magnets. The number of particles to be deposited in each position varies strongly within the same iso-energetic layer. In order to maintain the required precision on the number of particles delivered to each spot, the intensity is reduced when spots that require low number of particles are present in a layer. A method to shorten the irradiation time based on variable intensity within the same layer is presented. This method can be used also with a betatron based extraction scheme. The results of preliminary implementation and test are reported.


Development and dosimetry of the 25 MeV proton irradiation line of the PRECy platform for radiobiology studies

M. Rousseau1

1Université de Strasbourg, IPHC, Strasbourg, France

In vitro and in vivo research platforms with protons that reflect patient's irradiation conditions are needed. A 25 MeV cyclotron usually producing radio-isotopes, was used for developing such a platform for radiobiology studies.

An homogeneous irradiation field with a suitable proton flux is obtained by means of an aluminum diffusion sheet, then is extracted in air. The size of the irradiation field is defined using collimators (from 2 mm to 18 mm diameter) depending on the radiobiological studies. To allow energy modulation of the proton beam, a set of varying Al thicknesses is used to obtain a power range of 4.03 to 24.85 MeV.

Various dosimetric measurements have been made to validate this platform. An accuracy of less than 4% was measured on the total dose deposition with a heterogeneity of less than 1% on the diameter of the irradiated field

In conclusion, experimental results demonstrate that our 25 MeV proton platform is operational and allows precision irradiation for preclinical research in vitro and in vivo with a dose rate ranging from 0.1 Gy / min to 50 Gy / s and a range in LET for in vitro measurement from 2 to 10 MeV/micron.


Advanced beam delivery technology for carbon ion radiotherapy

K. Shinomiya1, T. Yazawa1, Y. Iseki1, Y. Kanai1, Y. Hirata1, J. Powers2

1Toshiba Energy Systems & Solutions Corporation, New Technology Project Engineering Department, Kanagawa, Japan, 2Toshiba America Energy Systems Corporation, Nuclear Technology Applications, Charlotte, NC, USA

Carbon ion radiotherapy (CIRT) has progressed internationally in countries such as Japan, China, Italy and Germany, with substantial clinical experience. The PTCOG particle therapy patient statistics data updated to the end of 2017 indicates that there were 25,702 patients treated with carbon ions. The National Institute of Radiological Sciences (NIRS) in Japan has been a leading center in the clinical application since 1994, and has treated nearly half of this total population, with 11,964 patients treated through March 2018, representing substantial clinical and medical physics experience. The Toshiba technologies have been developed with the close collaboration and experience of the NIRS.

Toshiba provides CIRT technology which features:

  1. compact rotating gantry with superconducting (SC) magnets,

  2. ultra-compact scanning system,

  3. 3D fast scanning irradiation with energy variation,

  4. respiratory-gated irradiation with markerless fluoroscopic tracking.

These devices make it possible to treat moving tumors with gating and fast rescanning, which is the world's first application with scanning beam (Figure 1). Toshiba also provided the CIRT rotating gantry at NIRS, which applies SC magnets in the beam line for more effective bending, allowing reduction of the overall size of the device; clinical operation of the gantry started in May 2017. Using SC magnet technology and the ultra-compact scanning system, the size of the gantry has been further reduced in the on-going projects for Yamagata University and Yonsei University to be comparable to proton gantries (Figure 2). This presentation will provide insight on these state-of-the-art devices for CIRT delivery.


Monte Carlo study of short-lived isotopes production for online dose verification in particle therapy

A. Solovev1, A. Chernukha1, V. Saburov1, P. Shegai2, S. Ivanov3, A. Kaprin4

1A. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Radiation biophysics, Obninsk, Russian Federation, 2National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Center of innovative radiological and regenerative technologies, Obninsk, Russian Federation, 3A. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Administration, Obninsk, Russian Federation, 4National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Administration, Obninsk, Russian Federation

Online dose monitoring in particle therapy is a crucial part of a modern era technology. Hadrons travelling through matter may interact with atoms using strong nuclear force. One of the results of these interactions are the beta-emitting isotopes with various lifetime. The 3D distribution of the resulted annihilation gamma rays is well corresponded with the initial Bragg curve. These events ultimately lead to the practical range and dose verification of the initial particle beam in matter.

In this study we simulated using Geant4 the production of short-lived (half-life < 1 min) and long-lived isotopes from monoenergetic beams of protons and carbon ions in homogeneous phantoms of water, PMMA and ICRU tissue. In this study we demonstrate that the production of short-lived isotopes and its annihilation gammas is enough to be registered on the top of long-lived background for ideal detectors. We suppose that registration of gamma lines from short-lived isotopes between the spills of synchrotron extraction might be useful to reconstruct dose within the single spill inside the human body.

Overall, the online dose verification is a promising part of a modern era technology for particle therapy offering a great extent to currently existing quality assurance procedures. In vivo dose verification might be useful for designing new therapeutic schemes and regimes of particle therapy.


Normalization of secondary radiation doses in proton radiotherapy: Can we do it in a better way?

L. Stolarczyk1,2, N. Mojżeszek2, O. Van Hoey3, J. Farah4, C. Domingo5, V. Mares6, O. Ploc7, S. Trinkl8, R. Harrison9, P. Olko10

1Skandionkliniken, Medical Physics Group, Uppsala, Sweden, 2Institute of Nuclear Physics, Cyclotron Center Bronowice, Kraków, Poland, 3The Belgian Nuclear Research Center SCK•CEN, Institute for Environment- Health and Safety, Mol, Belgium, 4Paris-Sud University Hospitals-, Radiology and Nuclear Medicine Department, Le Kremlin-Bicêtre, France, 5Universitat Autònoma de Barcelona, Departament de Física, Barcelona, Spain, 6Helmholtz Zentrum München, Institute of Innovative Radiotherapy, Neuherberg, Germany, 7Nuclear Physics Institute of the CAS, Department of Radiation Dosimetry, Prague, Czechia, 8Federal Office for Radiation Protection, External and internal dosimetry- biokinetics, Oberschleissheim, Germany, 9University of Newcastle upon Tyne, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom, 10Institute of Nuclear Physics, Division of Applications of Physics, Kraków, Poland

Currently in the literature unwanted doses related to proton radiotherapy are normalized only to the treatment dose. This prevents a close comparison between different experiments since the results are strongly dependent not only on the experimental setup but also on primary beam energy, target size and location.

As a continuation of EURADOS WG9 study (Mojżeszek, 2017), environmental doses from stray neutrons and γ-rays for a PBS treatment technique were collected as a function of field size, beam range and modulation width. The experiment was carried out in the Cyclotron Center Bronowice (Poland) using TEPC (HAWK) and six rem-counters (WENDI-II, LB6411, a regular and an extended-range NM2B). Detectors were positioned around an RW3 (30cm x 30cm x 60cm) phantom at seven points inside the IBA gantry room with a PBS dedicated nozzle.

H*(10) strongly depends on the detector position, with the largest values along the beam direction. Furthermore, variations of neutron H*(10) were observed with changes in range and field size. H*(10) for 10cm2 field size and 10cm modulation varied between 7.0μSv/Gy at range 15cm and 25.4μSv/Gy at range 30cm at 2.25m distance and 135-degree angle with respect to the beam axis. Moreover, the presence of a range shifter increases unwanted doses by almost a factor of 2.

The presented results may help in understanding H*(10) variation with beam parameters such as dose, energy, modulation width or field size and finally in the development of analytical models of secondary radiation doses implemented in treatment planning systems.


Dosimetric evaluation of commercial proton spot scanning Monte Carlo dose calculation in small fields for ocular tumors

A. Toltz1, Z. Nevitt2, C. Bloch1, T. Wong2, P. Taddei1, J. Saini2, R. Regmi2

1University of Washington, Radiation Oncology, Seattle, WA, USA, 2Seattle Cancer Care Alliance Proton Therapy Center, Physics, Seattle, WA, USA

Motivation: Ocular treatment with proton therapy is conventionally delivered on a dedicated beam-line, providing the advantage of sharp lateral and distal dose-falloffs. Newer pencil beam scanning-only proton centers lack dedicated beam-lines and thus do not treat ocular lesions. We report the development of an extended-snout-applicator (ESA) that retrofits with spot scanning snouts to provide the dosimetric and physical benefits of a dedicated snout for ocular radiotherapy.

Methods: A commercial Monte Carlo (MC) dose calculation algorithm for proton spot scanning was compared to measurements with the ESA in water using a microDiamond detector, PinPoint chamber, and Gafchromic film. Output factor, range, and lateral profiles at varying depths were assessed for proton beams of range 4 cm and 6 cm in tissue and five small circular fields varying from 1.0 cm – 3.0 cm in diameter.

Results/Conclusion: Ranges of pristine Bragg peaks in water (R80) were found to agree to within 0.5 mm (RMSE = 0.2 mm) and 0.8 mm (RMSE = 0.3 mm) for 4 cm and 6 cm ranged beams, respectively, between measured and calculated R80 for all fields. Preliminary results show greater than 95% pass rate between all measured and calculated lateral profiles (gamma criteria: 2%, 2 mm). Initial analysis shows good agreement (within 3%) for output factors for both beam ranges for all but the smallest field size (under investigation), supporting clinical implementation of the ESA for the treatment of ocular tumors.


Design considerations of the range shifter in a scanning nozzle for the compact superconducting cyclotron SC200

M. Wang1, S. Yuntao1, Z. Jinxing1

1University of Science and Technology of China, Science Island Branch of Graduate School, Hefei, China

The compact superconducting cyclotron SC200 for proton therapy is designing by ASIPP and JINR will able to accelerate protons to the energy 200 MeV with the maximum beam current of 400 nA. The beam energy is modulated using a degrader, which can reduce the energy between 70∼190 MeV. In order to apply the pencil beam scanning (PBS) technique to tumors located proximal to the minimum range, a range shifter is needed to insert in the nozzle to degrade the beam energy. However, the range shifter will broaden the proton beam and effect the dose distribution in the patient. In this paper, a range shifter model designed for the nozzle of SC200 was introduced and its influence on the proton beam was studied in detail. First, the investigation of range shifters of various material composition affect spot size in different geometries was performed. Then, using the analytic approximation and Monte Carlo methods, the effects of the gap between the range shifters and the mounting errors on the proton beam were carefully evaluated. Moreover, the mechanical analysis of the PBS nozzle with range shifter was performed using the SolidWorks. The results show that the polyethylene is the desirable shifter materials and designed model can meet the clinical requirement. Besides, the results presented here may prove useful for range shifters design of other research groups.


End to end simulations of the Clatterbridge Eye Proton Therapy beamline

J.S.L. Yap1,2, M. Hentz3, J. Silverman3, S. Jolly3, S. Boogert4, L. Nevay4, A. Kacperek5, R. Schnuerer1,2, J. Resta-Lopez1,2, C. Welsch1,2

1University of Liverpool, Physics, Liverpool, United Kingdom, 2Cockcroft Institute, Quasar Group, Warrington, United Kingdom, 3University College London, UCL High Energy Physics, London, United Kingdom, 4Royal Holloway University of London, John Adams Institute, London, United Kingdom, 5The Clatterbridge Cancer Center, The National Eye Proton Therapy Center, Wirral, United Kingdom

The world's first hospital proton beam therapy facility, based at the Clatterbridge Cancer Center, UK has successfully provided treatment for ocular cancers over the past 30 years. A 60 MeV beam of protons is produced and transported through a passive delivery system which enables the precise delivery of uniform dose at the target site. In addition to the long history of clinical use, the facility supports a rich program of experimental work and as such, there is a need for an accurate and reliable simulation model to fully characterize the beam. We present recent developments of a complete end-to-end simulation model of the Clatterbridge beamline, from the extraction point of the cyclotron all the way to the treatment nozzle. A comprehensive model of the delivery system was developed using the Monte Carlo simulation toolkit Geant4 and expanded to include precise CAD models of the treatment beamline. Upstream of the treatment room, an extensive beam dynamics study was performed to determine beam parameters utilized with the accelerator design code Beam Delivery Simulation (BDSIM). Experimental measurements were carried out to validate the accuracy of the simulated beams of both codes and findings were implemented in the combined model. The consolidation of information of the entire beamline is achieved through the superior geometry modelling and beam transport capabilities of BDSIM and recent results are discussed. The final model is anticipated to be available for wide use as a verified, standard simulation model for all related work performed with the Clatterbridge proton therapy beamline.


Physical design of gantry delivery system for SC200 superconducting proton cyclotron

X. Zeng1, J. Zheng1, M. Li1, M. Wang1, M. Han2, Y. Song1

1Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, China, 2Hefei CAS Ion Medical and Technical Devices Co., Ltd, Hefei, China

The SC200 superconducting proton cyclotron is a key project supported by the local government of Hefei, China and the Chinese Academy of Sciences. The project is based on an isochronous superconducting cyclotron that provides a 200 MeV fixed-energy proton beam. Such energy can be continually adjusted between 70 and 190 MeV using a wedge graphite degrader. The proton beam is then directed through beam transport system into gantry. In this paper, we present a new isometric gantry with downstream scanning nozzle scheme. For a 360-degree gantry, a double-waist round beam at the coupling point ensures the gantry beamline optics remain identical at all angles of rotation. Based on waist to waist theory, Beam line reverse, Round-beam method and TRANSPORT code, the emittance, momentum spread and maximum field and gradient was therefore determined. Moreover, the orbit distortion correction has been calculated with response matrix and SVD algorithm based on Madx. The results indicate that its physical design is reasonable and feasible. It can transfer the proton beam from 70 to 200 MeV to isocenter with a momentum spread no more than 1%. Currently the main components of gantry delivery system have been completed, such as magnets, mechanical structure and treatment nozzle. The magnetic fields of dipole and quadrupole magnets have been measured by hall mapping system and rotary coil measuring system. Testing of the mechanical part of gantry has also been done, whose deviation at the iso-center is extremely accurate and meets the design requirements of less than 1 mm.


Research and development of beam transport system of SC200 superconducting proton cyclotron

J. Zheng1, X. Zeng1, Y. Song1, M. Li1, M. Wang1, M. Han2

1Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, China, 2Hefei CAS Ion Medical and Technical Devices Co., Ltd, Hefei, China

The dedicated new medical facility SC200 with one gantry treatment room and one fixed beam room is under development in ASIPP (Institute of Plasma Physics Chinese Academy of Sciences). A 200 MeV/500 nA proton beam will be extracted from an isochronous superconducting proton accelerator. And then the beam transport system will guide the accelerated beam to one treatment room at a time. To enhance compact form of beam line, the main trunk line based on the beam optics design will be achromatic by 63-degree dipole magnets for minimum area. The layout of beam transport system is mainly consisted of a series of discrete magnets such as dipoles, quadrupoles and steering magnets. The beam transport system also employs an energy selection system, including an energy degrader which can modulate the proton beam energy from 200 to 70 MeV continuously, two collimators which can adjust beam emittance to 16π mmmrad, and a momentum slit. Currently the main components of beam transport system have been completed such as magnets, degrader, beam monitors, gantry and treatment nozzle. Moreover, the magnetic fields of dipole and quadrupole magnets have also been measured by hall mapping system and rotary coil measuring system. Testing of the mechanical and control aspects of degrader, gantry and treatment nozzle system has also been done separately. In the next stage, we will focus on system commissioning such as the measurement of the beam profile, position, current, loss, energy and energy spread.

Physics: Beam Delivery and Nozzle Design Poster Discussion Sessions, PTC58-0111

Proton range uncertainty due to momentum deviation

S. Shiraishi1, K. Furutani1

1Mayo Clinic, Radiation Oncology, Rochester, MN, USA

In an accelerator, dispersion relates beam momentum offset to positional beam displacement. Because spot position is continuously monitored during treatments using a spot position monitor (SPM) and large deviations abort beam delivery, dispersion at the SPM can set an upper bound on delivered momentum deviation. Our institution uses a Hitachi PROBEAT V synchrotron that delivers beams of 70 to 230 MeV to four treatment rooms with gantries. The SPM is in the nozzle, approximately 0.5 meters upstream of the treatment isocenter. We measured dispersion at the SPM by varying the magnetic field strengths of all transport line optics, which effectively changed the beam's momentum offset, δ. For all four gantries, dispersions of 230 MeV beams were measured for a gantry angle; in one gantry, dispersions of 70 and 140 MeV beams were also measured. Momentum offset corresponding to ±1 mm shift was converted to fractional range uncertainty. When dispersion was approximately zero at the SPM, dose rate measurements were used to identify momentum deviation that could reach the patient. The measured dispersion was both energy- and gantry-dependent. Shifts in beam positions as functions of δ for 230 MeV beams are shown in Fig. 1 (a); range uncertainty varied from 0.4% to 1.9% across the four gantries. The corresponding plot for the three different energies is shown in Fig. 1 (b); range uncertainties varied from 0.7% to 1.1%. Future work will involve dispersion measurements at other gantry angles to set an upper bound of momentum deviation that can reach the patient.


Using non-linear beam optics to shape the lateral penumbra of a proton beam: Proof of concept

A. Holm1, S. Korreman2, J.B.B. Petersen1

1Aarhus University Hospital, Medical Physics, Aarhus C, Denmark, 2Aarhus University Hospital, Department of Oncology, Aarhus, Denmark

Background: Pencil-beam scanning (PBS) is often used in proton therapy to allow for multi-field optimization with fluence modulation without patient specific field-shaping devices. PBS may, however, result in a larger lateral penumbra (LP) than techniques utilizing aperture blocks for field shaping. Beam apertures or MLCs, may be used to reduce the LP, but may also increase the ambient neutron flux. As an alternative solution, non-linear beam components can be used to shape the beam without introducing high Z components in the beamline. This study compares the LP of a pencil beam to an octupole-shaped beam.

Materials and Methods: A generic proton beamline with five quadrupoles and one octupole has been simulated using TraceWin for beam envelope computations and Monte Carlo simulations of the lateral beam distribution at the ISO-center (1.000.000 protons). All beamline input parameters, e.g. current, energy and beam spot sizes, are comparable to that of clinical delivery systems. The beamline was optimized for maximal sharpening of the lateral vertical penumbra. The lateral fall-off (LFO) is estimated by the 20%-80% distribution width.

Results and Conclusion: Examples of beam distributions and vertical beam profiles (VBPs) are shown in fig. 1. It is evident that the VBP changes from Gaussian-like to box-like when the octupole is switched on. The LFO for two energies, three spot sizes, and two octupole modalities are summarized in table 1. It has been demonstrated that with a simple beamline containing an octupole, the LP of a proton beam can be significantly reduced without using any collimation.


Stereotactical fields applied with a modified pencil-beam scanning nozzle and collimating apertures

C. Bäumer1,2, C. Fuenstes3, M. Janson4, A. Matic5, B. Timmermann6, J. Wulff1

1West German Proton Therapy Center, Medical Physics, Essen, Germany, 2DKTK – Deutsches Konsortium für Translationale Krebsforschung, Site Essen/Düsseldorf, Heidelberg, Germany, 3IBA pt, Clinical Solutions, Louvain-la-neuve, Belgium, 4RaySearch Laboratories, Proton Planning, Stockholm, Sweden, 5IBA pt, Local Team Essen, Essen, Germany, 6West German Proton Therapy Center, Department of Particle Therapy, Essen, Germany

The small fields employed in stereotactical radiation therapy require sharp lateral dose gradients, which are difficult to realize with the proton pencil beam technique. This holds especially true to shallow-seated tumors which require a range shifting block for energy degradation. The current work demonstrates a technical concept based on a slight modification of the pencil beam scanning mode of the IBA Universal Nozzle. A range shifter (6.3 g/cm2) is inserted in the beam path mounted in the wheel originally designed for the double scattering mode with a distance to the isocenter of 171 cm. Collimating brass apertures were mounted in the Snout180 extension. Proton fields were delivered in a service mode disabling the interlocks of the clinical mode. Lateral profiles were measured with the Lynx2D scintillation detector in conjunction with RW3 build-up plates and with EBT3 film. A beam model of the nozzle was established in the treatment planning system RayStation. Dose distributions were simulated with the Monte Carlo dose engine of RayStation. The experimental results show an 80%-20% lateral dose fall-off of 1.4 mm – 1.8 mm in air and 1.9 mm – 3.0 mm for water equivalent depths between 5 mm and 56 mm. In the figure lateral profiles with a 130 MeV field, 3 cm square aperture and air gap of 5 cm are presented as an example (measurement indicated by red line [1.9 mm lateral dose fall-off], simulation by green line). The measured lateral dose fall-off agrees with the simulated one on average within 0.1 mm.


Comprehensive approach to reduce proton dose application time with PBS

D. Meer1, S. Psoroulas1, T. Lomax1, D.C. Weber1,2,3

1Paul Scherrer Institut, Center for Proton Therapy, Villigen PSI, Switzerland, 2University Hospital Zurich, Department of Radiation Oncology, Zurich, Switzerland, 3University Hospital Bern, Department of Radiation Oncology, Bern, Switzerland

A reduction of the dose application time opens up new treatment options in proton therapy (PT), such as the treatment of mobile tumors during a single breath-hold, the efficient application of hypofractionation or to mitigate motion effects by rescanning. Ultimately, shorter irradiation times provide benefits for both patient comfort and the PT-workflow.

The irradiation time is primarily determined by the available dose rate at the iso-center. In addition, the duration depends on the reaction times of the fast scanning actuators as well as the time for the energy change. We will exploit the availability of high proton currents from the cyclotron and the minimal dead time of line scanning to optimize the field application time.

The PSI Gantry 2 provides typical energy changes faster than 100ms. The beam current from the cyclotron can be precisely modulated in less than 1ms. Beam intensity losses in the energy degrader system can be at least partially reduced at low proton energy with a different degrader material [1]. By combining the different technologies, our goal is to irradiate fields for small tumor volumes <250ml in less than 10s and to integrate it safely into clinical operation.

The effective irradiation time depends strongly on the geometry of the dose distribution, particularly so for re-scanning, which have dose-distribution with low spot doses that may benefit from line scanning [2]. Increasing the dose rate is particularly advantageous for high field doses such as hypofractionation. [1] A Gerbershagen et al 2016 Phys.Med.Biol. 61 N337. [2] G Klimpki et al 2018 Phys.Med.Biol. 63 145006.

Physics: Commissioning New Facilities, PTC58-0064

Commissioning of McLaren Proton Therapy System

B. Arjomandy1, B. Athar1, B. Tesfamicael1, A. Bejarano Buele1, J. Deemer1, V. Kozlyuk1, K. VanSickle1

1Karmanos Cancer Institute at McLaren-Flint, McLaren Proton Therapy Center, Flint, MI, USA

Introduction: McLaren Proton Therapy Center (MPTC) is equipped with a Radiance 330TM synchrotron which is capable of pencil beam delivery (70-330 MeV). The treatment rooms are equipped with a robotic couch for patient positioning and half gantry for beam delivery. The in-room imaging system is capable of acquiring planar and CBCT images while mounted from an independent x-ray gantry.

Methods and Material: The ionization depth doses for 70 to 250 MeV were measured using PTW water tank and Bragg peak chambers. An IBA Lynx was used to measure the beam sigma at isocenter as well as at four different positions relative to isocenter. The IAEA TRS 398 protocol was used to calibrate the delivered dose. The dose distribution was verified using gamma index analysis. The dose calibration and dose distribution were verified by IROC Houston for a prostate phantom. The gantry mechanical isocentricity was measured using an in-house fabricated device. Isocentricity shifts are accommodated by correcting the treatment couch positions for gantry sag for various gantry angles.

Results: The ranges of proton beams are verified to be within 0.5 mm of the tabulated CSDA values. The spots circularity is verified to be within 10% in X and Y axis. The positional accuracy of the spots is within 1.5% of the planned map. The gantry isocentricity is within 0.5 mm radius after couch correction.

Conclusion: The gamma analysis of dose distributions had a passing rate of >95% for 2%/2mm. Independent verification by IROC has verified our beam delivery calibration and accuracy.


Radiation safety and workload determination at the Groningen Proton Therapy Center (GPTC)

R. Bolt1, M.J. van Goethem1, J. Langendijk1, A. van t Veld1, S. Both1

1University of Groningen- University Medical Center Groningen, Department of Radiation Oncology, Groningen, Netherlands

Purpose: The UMCG-PTCG facility opened in Jan-2018 as a two-gantry proton facility. We report on the validation of the MCNPX-MC-simulations (F.Stichelbaut [1]) based shielding design relative to measurements .

Materials and Methods The beam usage was determined based on manufacturer (IBA,Belgium) provided logfiles (Fig.1) for a mix of pediatric, intra-cranial and Head & Neck (shallow located) targets . We performed measurements and determined dose outside the treatment rooms as a function of the facility workload. Stray radiation levels were logged at pre-determined locations using a FGH-40 with an Wendi-2 neutron detector during beam-on time. The Wendi-data was correlated to beam usage data based on time-stamps. Measurements during beam-off time were used to correct for fluctuations in background radiation, as background dose rate fluctuations have the same order as the stray dose rate.

Results and Discussion The log-file analysis made it possible to monitor beam usage on a day-by-day basis. Our actual beam usage increased approximately three times compared to our initial case-mix (which included deep seated targets, such as lung, prostate). In part, this increase may be explained by changes in the patient case-mix, we treat mainly shallow indications (H&N, CSA), resulting in lower energies and higher losses in the degrader/ESS. However, even at this increased yearly workload the measured radiation levels around our treatment rooms are well below the MC-predicted level of 100μSv/year.

Conclusion: The MC based shielding calculation-based predictions are conservative, overestimating the shielding requirements, even if the shallow targets increasing the cyclotron workload are predominantly treated.1) F.Stichelbaut IBA, private communications.


Feasibility study of multi-vendor integration between Eclipse, Mosaiq and ProteusOne system

K.L. Chen1, B. Wlodarczyk2, H. Wu1

1Willis-Knighton Cancer Center, Radiation Oncology, Shreveport, LA, USA, 2IBA, Proton Therapy, Louvian-La-Neuve, Belgium

Introduction: The popularity of compact proton therapy systems has increased in recent years, especially among existing established radiation oncology facilities that seek proton therapy as an addition to their service. With various combination of applications available from different vendors, this study aims to evaluate the workflow feasibility to integrate Eclipse treatment planning system (TPS), Mosaiq oncology information system (OIS), and ProteusOne proton therapy system (PTS).

Materials and Methods: The beam data acquired for existing TPS commissioning were entered in Eclipse TPS (version 15.5). In addition to depth dose curves and spot fluence profiles, Eclipse TPS requires beam lateral spreader (scanning magnets) information provided by IBA. Current Eclipse TPS provides nonlinear universal proton optimizer (NUPO) algorithm and proton convolution superposition (PCS) algorithm for optimization, and is capable for robustness optimization. Beam data validation is done by measuring absolute dose in a solid water phantom using a PPC05 parallel chamber. A prostate plan composed of two opposite lateral beams was created and imported into Mosaiq (version 2.64). The plan was delivered with IBA AdaptDeliver and dose distributions were obtained with MatriXX PT ion chamber detector array for gamma analysis.

Results: The absolute point dose measured in the solid water was 0.08 CcGE (-0.04%) different comparing to the TPS calculated dose. The average gamma analysis for the prostate plan at three different depths using 3% dose and 3 mm distance-to-agreement criteria showed 95% passing rate.

Conclusion: This study demonstrated that it is possible to integrate IBA ProteusOne with Eclipse TPS and Mosaiq OIS accurately.


Medical physics commissioning of SAPT therapy system

Z. Chen1, L. Shen2, D. Li3, Z. Zhao4

1Shanghai Advanced Research Institute- CAS- China, Shanghai Synchrotron Radiation Facility, Shanghai, China, 2Shanghai Advanced Research Institute- CAS, Shanghai Synchrotron Radiation Facility, Shanghai, China, 3Shanghai Institute of Applied Physics- CAS, Center for Applied Accelerator, Shanghai, China, 4Shanghai Advanced Research Institute- CAS- China, Shanghai Synchrotron Radiation Facility SSRF, Shanghai, China

A synchrotron-based proton therapy system in the Shanghai Ruijin Hospital Proton Center is currently under beam commissioning. It consists of two pencil beam scanning (PBS) treatment rooms (1 horizontal beam and 1 half-rotating gantry room), one eye treatment room and one experimental room. The accelerator and beam delivery systems are developed by scientists and engineers from Shanghai Synchrotron Radiation Facility (SSRF), Chinese Academy of Science, funded by Shanghai Advanced Proton Therapy project (SAPT). The Ruijin Hospital is responsible for the clinical. It's expected to be the first hospital-based proton therapy center for joint-research and development in China.

The PBS system has started commissioning in the horizontal-beam room before the end of 2017. The eye treatment system (cooperated with PSI, Switzerland) and rotation gantry has been installed and the commissioning is planned in the first half of 2019.

A brief overview of the SAPT therapy system, commissioning method and status will be reported. The therapy system performance and commissioning experience will be discussed.


What is the representative spot size to be used in the treatment planning system?

A. Fredh1, A. Bolsi1, F. Belosi1, N. Fachouri1, L. Placidi1, T. Böhlen1, J. Hrbacek1, A. Lomax1, D.C. Weber1, S. Safai1

1Paul Scherrer Institut, Center for proton therapy, Villigen PSI, Switzerland

Purpose: In Eclipse, a single spot size is defined for each energy, which is then assumed to represent the spot size for all positions and gantry angles with that energy. This work investigates the best definition of such a reference spot size.

Methods and Material: Measurements were performed on a Varian ProBeam facility using Varian (IAS), IBA (Lynx) and in-house scintillating-foil-CCD (CCD1) systems, and were compared using single central spots for 17 energies. Additionally, spot sizes were measured with the IAS for a central and 48 equally spaced spots over the full scan range (25x35cm) at 4 gantry angles (0°, 90°, 180° and 270°) and for 10 different energies. X and Y sigmas were then calculated for each, and the minimum and maximum sigma for each energy compared to the mean value and sigma of the central spot at 270°.

Results: The measurements with three devices show maximum deviations below 3% (Figure1). Table 1a summarizes the mean spot sigma for each energy and the difference of the max/min spot sizes compared to this mean. Sigmas of the central spots at 270°, and max/min differences to this, are reported in table 1b. X and Y sigma for all the measured spots deviate <9.5% from the mean value at the same energy, whereas when using the central spot at 270° as reference, deviations are up to 15% for high energies.

Conclusion: The energy specific mean spot size, averaged over 4 gantry angles and all spot positions, can be considered the most representative spot size for the ProBeam system.


Current status and future prospects of a carbon ion therapy facility project of Yamagata University

Y. Ieko1, T. Iwai1, K. Nemoto1, K. Suzuki1, T. Kanai1, Y. Miyasaka1, M. Harada1, H. Yamashita1, I. Kubota1, T. Kayama1

1Yamagata University, Faculty of Medicine, Yamagata, Japan

Construction of seventh carbon-ion therapy facility in Japan, East Japan Heavy Ion Center, Faculty of Medicine, Yamagata University, is near completion. The building is 45 m × 45 m × 27 m cubic design, smallest facility in the world, and connects directly to general hospital. A main synchrotron accelerator (a maximum energy of 430 MeV/u) with newly designed dipole magnets is located on the basement floor. There are two treatment rooms, horizontal and 360° rotating gantry, on the 2nd floor. Rotating gantry is even smaller than NIRS gantry using the superconducting technique and shortened scanning system. We chose RayStation (RaySearch Laboratories AB) as the treatment planning system which has very fast dose calculation engine to accurately calculate dose. In 2019, building construction and system installation will be completed, and acceptance testing and clinical commissioning will begin. After the commissioning work, first patient will be treated in spring 2020.


Preliminary range validation of two proton calculation models in Eclipse

M.F. Jensen1, P. Bræmer-Jensen1, P. Randers1, C.S. Søndergaard1, O. Nørrevang1, V.T. Taasti2

1Aarhus University Hospital, Danish Center for Particle Therapy, Aarhus N, Denmark, 2Memorial Sloan Kettering, Cancer Center, New York, NY, USA

The treatment planning system Eclipse offers two proton dose calculation models; analytical proton convolution superposition (PCS) and Monte Carlo (AcurosPT). The two models use different Hounsfield unit (HU) to stopping power ratio (SPR) conversion strategies and are therefore validated separately. PCS uses the standard HU look-up table (HLUT) to SPR, while AcurosPT uses a HLUT to mass density. The HLUTs are created from the same stoichiometric calibration and the calculation models are created from the same base data.

We present a preliminary range validation study. CT scans of a pig femur bone sample including marrow were acquired with a dual energy CT scanner, Edge (Siemens Healthineers, Forchheim, Germany) using Twin-beam mode. Pseudo mono-energetic images were generated with the Siemens Mono+ algorithm at 90 keV. The water equivalent thickness (WET) of the sample was measured at four different positions with a single proton spot at 220 MeV using a multi-layer ionization chamber (Giraffe, IBA Dosimetry). In Eclipse, the WET was determined by the difference in range between the integrated depth-dose curves with and without the sample for both models. All calculations were performed at the measurement positions and hereafter displaced by 1 mm in 4 directions perpendicular to the beam using robust evaluation and the Eclipse API. Both PCS and AcurosPT overestimate the WET with an overall average WET difference for PCS of 2.8% and for AcurosPT of 5.2%. Ongoing investigations are performed to further evaluate this by measuring through various homogeneous soft tissues as well as heterogeneous samples.


Commissioning of the synchrotron-based eye treatment therapy system in Shanghai Advanced Proton Therapy Project

H. Kong1, Z. Chen2, C. Yin2, M. Gu2, M. Liu2, Z. Zhao2

1Shanghai Institute of Applied Physics- Chinese Academy of Sciences, Department of Beam Measurement and Control, Shanghai, China, 2Shanghai Advanced Research Institute-Chinese Academy of Science, Department of beam measurement and control technology, Shanghai-China, China

The synchrotron-based proton therapy system in the Shanghai Advanced Proton Therapy Project (SAPT) is now under commissioning in Shanghai, China. There are four treatment rooms (one experiment room, one eye treatment room, one fixed-beam treatment room and one gantry room) in SAPT. In collaboration with the Center for Proton Therapy (CPT) at PSI, the design of the eye treatment nozzle and patient position system is same as that of OPTIS2 at PSI. However, to adapt the double scattering irradiation system to the SAPT synchrotron accelerator and therapy control system, a new irradiation control and verification system has been designed and implemented. It's very important to keep the beam quality and safety as same as the original system in PSI. For the patient, it's also important to keep the treatment time as short as possible while the SAPT synchrotron is quite different with the cyclotron and degrader at PSI. This report will introduce the overall design, implementation and preliminary commissioning result of the eye treatment room. We expect this treatment room will be the first dedicated proton eye treatment room in China.


Scanned proton beam performance and calibration on the Shanghai Advanced Proton Therapy Facility

H. Shu1,2, Y. Chongxian1,2, Z. Haiyang3, Z. Juan1,2, L. Ming1,2, Z.. Manzhou1,2, Z. Liying1,2, C. Kecheng1.2, D. Xiaolei1,2

1Shanghai Institute of Applied Physics, Chinese Academy of Sciences2019 Jialuo Road, Shanghai, China, 2Shanghai Advanced Research Institute, Chinese Academy of Sciences, No.99 Haike Road, Zhangjiang Hi-Tech Park, Pudong Shanghai 201210, China, 3Shanghai APCTRON Particle Equipment,2019 Jialuo Road, Shanghai, China

The Shanghai Advanced Proton Therapy Facility (SAPT) is a hospital-based facility constructed since December of 2014 and the first scanned proton beam line with a fixed horizontal nozzle was commissioned in October of 2017. The energy of proton beam is from 70MeV up to 235MeV extracted from a synchrotron accelerator, and the maximal scanning area of 40×30 cm2 (U×V) can be attained at the iso-center. In this article, the proton beam commissioning activities and the dose calibration for primary monitor chamber are described. The beam performance qualities according to the IEC-62667 medical standard were investigated, including the spot size in air, spot position, depth dose curves, profiles with various energies in water, and homogeneity of the scanned field as well. Consequently, the performance of main dose monitor has been studied and calibrated with each pseudo-monoenergetic proton beam individually. The calibration procedure is similar to the IAEA TRS-398 recommendation but being applied to a different effective measurement point to enable determination of dose to water in the plateau region. The measured dosimetric parameters could be as part of the clinical commissioning and quality assurance program to treat the patient.


Commissioning a proton therapy pioneer facility in Spain

A. Mazal1, J. Castro1, J. Freire1, M. Cremades1, L. Moral1, P. Rico1, C. Ares1, R. Miralbell1

1Quironsalud, Protonterapia, Pozuelo- Madrid, Spain

A proton therapy center is under construction in Madrid as part of the two pioneer centers in Spain (46.5 Mhab, 500 000 km2). It will be a Proteus one single room facility operated by the group Quironsalud-Fresenius (46 hospitals, 23 linacs, high complexity). The equipment will include a Mosaiq OIS, Raysearch TPS and a double energy CT scan. The equipment rigging has been performed on November 2018 and the first patient is planned at the end of 2019, with 3.5 years ramp-up to achieve figures in the order of 400 pats/year, including hypo-fractionated schemes. A team is being built with experts from abroad and internal training with a planned ratio of 27/400 staff/patients per year. National recommendations are being prepared by the SEOR (Spanish Society for Radiation Oncology). A combined approach is under discussion with other centers having a close schedule, with common initiatives to validate gold standard data, share human and material resources to optimize commissioning efficiency, to warranty training and to share expertise.


Beam commissioning of HIMM facility

J. Shi1, J. Yang1, J. Xia1, X. Zhang1, B. Wang1, Q. Li2, X. Liu2

1Institute of Modern Physics- Chinese Academy of Sciences, Accelerator Department, Lanzhou, China, 2Institute of Modern Physics- Chinese Academy of Sciences, Medical Physics Department, Lanzhou, China

Heavy ion medical machine (HIMM) is the first Chinese heavy ion accelerator facility developed for cancer therapy. The facility contains two ECR ion source, a cyclotron injector, a synchrotron, 5 nozzles and the beam delivery systems. It can provide the carbon beam with energy from 120-400 MeV/u and intensity from 1e7 ppp (particle per pulse) to 1.2e9 ppp in each nozzle. The uniformity of the radiation field in the terminals is better than 106% after scanning. The results of the HIMM beam commissioning are reported in this paper.


Design the prototype of environmental inspection robot in radiation control area: An example of the proton therapy cyclotron control area

C.C. Sung1, W.P. Chen2, T.Y. Liao1

1Kaohsiung Chang Gung Memorial Hospital, Proton Therapy Center, Kaohsiung, Taiwan, 2National Kaohsiung University of Applied Sciences, Department of Electrical Engineering, Kaohsiung, Taiwan

In order to reduce the radiation dose of workers, The high-radiation control area monitoring and inspection work, need to consider the allowable value of personnel radiation, the current high-radiation control area relies on monitoring equipment to operate, but it still depends on the location of the photographic equipment, the image resolution, and its environmental changes such as temperature cannot be immediately sensed, and the most basic work, such as the cleaning of dust, still depends on manpower.

Therefore, this study proposes a cleaning robot that maps large indoor spaces using laser scanning and can avoid obstacles. The chassis of the robot has independent primary wheels and auxiliary wheels as power and support. Direct current is employed to power the vacuum cleaner and the robot's drive motor, to prevent power loss. An indoor facility undergoes three-dimensional laser scanning, and the cleaning space is then mapped through matrix graphics; The distance to the wall, measured by the laser rangefinder, is employed as a reference for the correction of the robot's movement. The proposed robot was shown to clearly identify obstacles through laser scanning and successfully avoid them during the cleaning process to complete the task along the pre-planned route. It can reduce the radiation dose of workers and monitor the high-radiation control area.


Clinical commissioning of heavy-ion treatment facility Osaka-HIMAK

M. Takashina1, N. Hamatani1, T. Tsubouchi1, M. Yagi2, T. Kanai1, J. Mizoe3

1Osaka Heavy Ion Therapy Center, Division of Medical Physics, Osaka, Japan, 2Osaka University, Graduate School of Medicine, Osaka, Japan, 3Osaka Heavy Ion Therapy Center, Division of Radiation Oncology, Osaka, Japan

The purpose of this work is to ensure safe operation of the new carbon ion therapy system Osaka-HIMAK (Heavy-Ion Medical Accelerator in Kansai).

Osaka Heavy-ion Therapy Center has three treatment rooms. Two of them (room 2 and 3) have horizontal and vertical ports, and another one (room 1) has horizontal and 45-degree ports. The two ports in the same room share a nozzle, which includes dose monitors, range shifters and ripple filters, and moves between the ports rotating around the isocenter. The respiratory-gated irradiation system is introduced in the room 1 and 2, and in-room CT will be installed in the room 2. The clinical commissioning had been done for the patient positioning system, the respiratory-gated irradiation system (and method), the beam delivery (raster scanning) system, and the treatment planning system (RayStation Doctor for delineating targets and organs and evaluating dose distributions, and VQAPlan for planning). We adopt the mixed-beam model as the biological model for treatment planning, and the so-called Schneider's method to derive the conversion table between CT value and the relative stopping power ratio.

The clinical commissioning of the room 3 had been completed by 15 October 2018, and the first treatment was carried out in 16 October. The treatment in the room 1 and 2 were also started sequentially after the clinical commissioning of each room was completed.

The eleventh carbon ion therapy facility had safely started the treatment in October 2018.


Preparing for helium therapy

U. Titt1, D. Mirkovic1, P. Yepes2, Q. Wang2, D. Grosshans3, M. Bangert4, H.P. Wieser4, R. Mohan1

1University of Texas- M. D. Anderson Cancer Center, Radiation Physics, Houston, TX, USA, 2Rice University, Physics, Houston, TX, USA, 3University of Texas- M. D. Anderson Cancer Center, Radiation Oncology, Houston, TX, USA, 4DKFZ, Physics, Heidelberg, Germany

Charged particle therapy utilizing helium ions is currently being discussed as a viable alternative to carbon therapy, particularly for pediatric therapy. Ongoing technological advances may provide novel designs of treatment machines compact enough to fit into facilities of the same size as for proton therapy. To understand the challenges and possible benefits of a helium facility, we started to investigate several aspects related to a helium beam line and treatment planning with helium beams.

A Monte Carlo model characterizing a heavy ion beam line, similar to equipment used in Japan and in Europe, was employed to investigate the properties of helium beamlets in air and in a water-phantom. The range in water, longitudinal and lateral dose profiles, as well as spot sizes and energy distributions of primary and secondary particles along the central axis were the first parameters to be investigated. The impact of (passive) beam line components, such as energy filters, beam profile and spot position monitors, resulting in additional scattering, secondary particle production etc., are being evaluated in detail. We will use the data to configure the ‘matRad' treatment planning system in order to evaluate the clinical properties of helium therapy plans.

In the future, we plan to design and perform high precision clonogenic essays, and small animal experiments in order to determine the biological effectiveness of helium compared to protons and carbon ions.


Status and evolution of the TOP-IMPLART Project

M. Vadrucci1

1Enea, Development of Particle Accelerators and Medical Applications, Frascati RM - Italy, Italy

The TOP IMPLART is a compact proton linac dedicated to cancer therapy. The accelerator up to 150 MeV is under construction. It consists of a commercial 7 MeV proton Linac produced by AccSys-Hitachi, operating at the frequency of 425MHz, and of a 3-GHz medium energy segment using commercially available S-band RF power systems. This machine is characterized by a small output beam size, a short beam pulse width and a high repetition rate, making it similar to the electron linacs used for cancer therapy. The TOP IMPLART peculiarities results in a compact design with reduced facility and operating costs with respect to conventional accelerator employed in the cancer proton therapy systems. In this paper the state of the art and the objectives of the TOP IMPLART project are described.


Current status and future plan of HIMM in China

G. Xiao1, X. Cai1, Q. Li1, J. Shi1, G. Li1, Y. Yuan1, R. Lu1, X. Zhang2, G. Sun2

1Chinese Academy of Sciences, Institute of Modern Physics, Lanzhou, China, 2Chinese Academy of Sciences, Lanzhou Kejintaiji Corporation Ltd., Lanzhou, China

A hospital-based tumor therapy facility HIMM (Heavy-Ion-Medical-Machine) was developed, and two demo centers of heavy-ion-tumor-therapy facility HIMM were built in Wuwei and Lanzhou, Gansu, China, respectively. HIMM Wuwei is the first homemade heavy ion accelerator for tumor therapy with independent intellectual property rights. HIMM Wuwei got the first beam in December 2015, and then received registration detection by the authorized third part including performance test, electrical safety test, EMC test, software (including treatment planning system TPS) test and environment test and so on. Since 2014 China Food and Drug Administration (CFDA) issued many new supervision regulations of medical devices. With thousands sets of medical electrical components, heavy ion therapy facility is considered the largest medical equipment in the world, and the registration detection is a huge effort and very time-consuming. HIMM Wuwei passed the examination of CFDA and obtained the qualified report of the authorized third part in April 2018. According to the regulations of national medical device supervision in China, the clinical trials of 47 patients were followed after passing the registration detection. HIMM Wuwei started the patient treatment on November 6, 2018. The first clinical trials with carbon beams were carried at vertical+horizontal treatment terminal with uniform scanning and horizontal treatment terminal with spot scanning. The clinical trials of 47 patients are planned to be finished in February 2019, and the follow-up visit of three months will be followed thereafter.


Commissioning of the Shanghai Advance Proton Therapy

M. Zhang1, L. Deming2, O. lianhua3

1Shanghai Advanced Research Institute-CAS, Accelerator Physics and RF, Shanghai, China, 2Shanghai Institute of Applied Physics, Accelerator Application, Shanghai, China, 3Shanghai Advanced Research Institute, Power Supply, Shanghai, China

Shanghai Advance Proton Therapy (SAPT) is a dedicated facility based on synchrotorn for cancer treatment in China. The commissioning of the accelerator started at the end of April 2017, and the proton beam has been already transported to the treatment room. This paper shows the commissioning results of synchrotron and transport line.

Physics: Commissioning New Facilities Poster Discussion Sessions, PTC58-0113

Physical characteristic measurements for the neutron beam generated by the linac-based neutron source for BNCT in University of Tsukuba

H. Kumada1, K. Takada2, S. Tanaka1, Y. Matsumoto1, F. Naito3, T. Kurihara3, K. Nakai1, A. Matsumura1, H. Sakurai1, T. Sakae1

1University of Tsukuba, Proton Medical Research Center, Tsukuba- Ibaraki, Japan, 2Gunma Prefectural College of Health Sciences, Department of Radiological Technology, Maebashi- Gunma, Japan, 3High Energy Accelerator Research Organization, J-PARC Accelerator Division, Tsukuba- Ibaraki, Japan

Introduction: The University of Tsukuba is being developed a linac-base neutron source (iBNCT) for boron neutron capture therapy (BNCT). The device had been completed to produce and we have carried out the commissioning and conditioning to generate neutron beam with the high current proton beam. Fig.1 shows the linac of the iBNCT neutron source device. At present, various characteristic measurement experiments have been performed to verify the practicability and applicability of the neutron beam to actual clinical trials using the device.

Materials and Methods: Various neutron irradiation experiments with a rectangular water phantom were performed. For the measurement of the thermal neutron flux, gold wires were set inside the phantom. And many TLDs were also set in the phantom to measure gamma-ray dose rate distribution. In the experiments, average proton beam current was set to 1.4 mA. We had also evaluated degradation characteristic for beryllium target.

Results and Discussions: Both of the maximum values for thermal neutron flux and for gamma-ray dose rate were approximately 7.8 e + 8 (n/cm2s) and 1.8 Gy/h at 2 cm depth in the phantom, respectively. And the beryllium target had received over 2,000-coulomb proton beams until now, but neutron intensity has not decreased at all. This received proton amount is comparable to the amount that can emit neutrons that can treat more than 500 patients.The results for the experiments demonstrated the device can produce proper epithermal neutron beam applicable to BNCT treatment. Based on the results, we plan to perform the non-clinical study.


Clinical commissioning of the first proton therapy facility in India

D. Shamurailatpam1, K. P1, N. Mp1, M. A1, G. Kg1, R. T1, S. C2, R. J2

1Apollo Proton Cancer Center, Medical Physics, Chennai, India, 2Apollo Proton Cancer Center, Radiation Oncology, Chennai, India

Our aim is to summarize the clinical commissioning of first proton therapy (PT) facility in India. The Apollo Proton Cancer Center (APCC) is a three-room PT facility equipped with ProteusPlus, Leoni 6D Robotic couch, RayStation-TPS and MOSAIC-OIS. ProteusPlus comprises a C230 isochronous cyclotron, dedicated pencil beam scanning nozzle, orthogonal kV-planar imaging and CBCT for image guidance. All tests related to electro-mechanical, safety, imaging and proton beam characteristics and their short-term reproducibility were carried out following protocol from IBA and the Atomic Energy Regulatory Board of India and results were within the prescribed tolerance limit.

The measurement of IDD, spot profile at different air-gaps, and absolute MU calibration were performed from 70.18-226.2 MeV in 5 MeV increment following recommendation of RayStation beam-modelling guide and were commissioned both for pencil beam and Monte Carlo algorithm. Mass-density to HU calibration curve of 85cm bore CT (AcquilonLB) were studied using CIRS head and thorax phantom for single and multiple inserts of inhomogeneity for three scanning protocol with and without metal artefact reduction algorithm and were commissioned in RayStation. Validation of TPS were performed through absolute and planar dose measurement. End-to-End test were performed using Head&Neck anthromorphic phantom. Accurate delivery of planned dose and stress test were performed for five clinical sites from AAPMTG-166 patient database. Planned and measured fluence at different depths agrees with gamma values of 3%at3mm above 95% (mean 98.3,SD=1.4).

The performance of PT facility at APCC is well within the prescribed limit and will provides an access to patients from India and neighbouring countries.


From commissioning to treatment with the ProteusOne at the Normandy Particle Therapy Center

T. Tessonnier1, A. Rozes1, P. Dutheil1, A. Batalla1, A. Vela1

1Center François Baclesse, Radiation Oncology, Caen, France

The Normandy Particle Therapy Center (CYCLHAD) began treating patients with the Center François Baclesse (CFB) in July 2018 using the IBA Proteus One solution after three weeks of acceptance testing and two-month commissioning. After 5 months, more than 20 patients have completed their treatment. The CYCLHAD center Proteus One is equipped with the IBA S2C2 (superconducting synchrocyclotron), a 220° compact gantry, stereoscopic imaging system and a 6D Leoni Orion System robotic couch.

This work summarizes and presents the various steps of the system characterization as well as machine and patient specific quality assurance (QA) program.

The proton beam system characterization and calibration presented were performed in order to comply with the RayStation treatment planning system (TPS) (RaySearch Laboratories) requirements:

  • Integral depth dose (IDD) measurements

  • Single spot measurements

  • Absolute dose calibration

Among the validation tests presented, several volumes (3x3x3cm3, 6x6x6cm3, 10x10x10cm3) centered at different depth were generated and compared to measurements with several detectors. Further testing with anthropomorphic head phantoms were performed.

Patient and Machine QA procedure, and the time needed to performed them, will be presented.

These validations tests and QA procedure ensure the reliability of the proton system for clinical activities.


Proton radiation beam matching and patient transfer workflow among rooms in a multi-vendor software environment: Conveniences, challenges, and potential solutions

S. Rana1, J. Bennouna1, A. Gutierrez1

1Miami Cancer Institute, Radiation Oncology, Miami, FL, USA

Purpose: Proton radiation beam matching option is available for a multi-room proton therapy center. The purpose of this work is twofold: First, as the first proton center to become clinical with a unique combination of RayStation, ARIA, and adaPT-IBA-system, we highlight the challenges and potential solutions for patient transfer workflow among different beam matched rooms in a multi-vendor software environment. Second, we present the comprehensive dosimetric results of proton beam matching for an IBA ProteusPLUS PBS proton system.

Methods: The measured proton beam matching parameters for each treatment room include: spot profile, absolute dose output, integral depth dose, range and modulation, and patient-specific QA results of various clinical cases. PBS proton and imaging (kV-planar and CBCT) machines are configured in RayStation, ARIA, and adaPT to facilitate patient transfer from one room to another.

Results: Although three gantries are beam matched dosimetrically, several challenges and potential solutions related to patient transfer among rooms were identified within ARIA and IBA system. Our current beam matching measurements include energies from 70-225 MeV with an increment of 5MeV. The spot size and range measurements among rooms were found to be within ±5%/±0.25mm and ±1mm, respectively, of each other. Absolute dose output was within ±2% with exception at lower energies. More comprehensive measurements at every 2.5MeV and various gantry angles are underway.

Conclusion: Beam matching provides the convenience of treating the same patient in any given room. However, patient transfer among rooms using ARIA and adaPT is non-trivial with several in-house solutions including changes in machine configurations.


Dosimetric verification at the Wuwei Heavy Ion Therapy Center using anthropomorphic phantoms

Q. Li1, P. He1, X. Liu1, G. Shen1, Z. Dai1, Y. Ma1, W. Chen1, G. Xiao2

1Institute of Modern Physics- Chinese Academy of Sciences, Medical Physics, Lanzhou, China, 2Institute of Modern Physics- Chinese Academy of Sciences, Nuclear Technique, Lanzhou, China

The facility of Heavy Ion Medical Machine (HIMM) at the Wuwei Heavy Ion Therapy Center has passed the inspection of China's Food and Drug Administration. To demonstrate the suitability of the HIMM facility for clinical trial, dosimetric verification using anthropomorphic phantoms was conducted for treatment plans under the dose delivery with uniform pencil beam scanning. The head-and-neck section and thoracoabdominal part of an anthropomorphic phantom with Farmer chambers were scanned under a planning CT scanner with 1.5mm slice thickness, respectively. Using the two-set CT images acquired, virtual planning target volumes were delineated in ways that the chamber's sensitive volume was located in the center, proximal end and distal end of the target volumes, respectively. Then treatment plans were designed using a carbon-ion radiotherapy treatment planning system, which was dedicatedly developed for HIMM. The treatment plans were executed in the HIMM facility and dose measurements were taken. Additionally, respiratory signals were virtually produced and gating irradiation was conducted for a plan using the thoracoabdominal phantom. The deviations between the planned and measured doses were less than 1.70% for the centers of the spread-out Bragg peaks (SOBPs), 3.20% for the proximal positions and 5.44% for the distal ends, respectively. In the case of the respiratory gating irradiation, the dose divergence was less than 0.3% in the center of the SOBP; however, the irradiation time compared to that without gating increased by a factor of 2. Thus, the passive beam delivery of the HIMM facility dosimetrically meets the requirements for subsequently clinical trial.


Proton beam matching

J. Lambert1, J. Clorley2, J. Pandey3, C. Chirvase3, M. Osborne4, E. Ilsley4, I. Di Biase1, J. Pettingell1

1Rutherford Cancer Centers, Group, UK wide, United Kingdom, 2Rutherford Cancer Center, South Wales, Newport, United Kingdom, 3Rutherford Cancer Center, North East, Bedlington, United Kingdom, 4Rutherford Cancer Center, Thames Valley, Reading, United Kingdom

In conventional radiotherapy linacs are beam matched to allow patients to be treated on different machines for ease of scheduling or in the event of downtime. In proton therapy this has proved to be more difficult, in part due to the difference in hardware and the beam optics between the cyclotron/synchrotron and different treatment rooms. With the advent of standardised hardware for single room centers it may now be more feasible to beam match proton therapy gantries.

The beam properties that need to be matched include the spot size, shape of the Bragg peak, range, and dose per MU, all of which are as a function of energy. How well they match will determine if a patient can be treated at a different site for their entire treatment, a few fractions in the event of downtime or if a replan is necessary before any treatment.

We are aiming to have a network of proton therapy sites that are all beam matched with patient plans created using a single beam model. Measurements performed at three of the sites will show if this is possible or if patients could be treated for a limited number of fractions during downtime at one site.


Design and construction of accelerator-based boron neutron capture therapy facility with multiple treatment rooms at Southern Tohoku BNCT Research Center

T. Kato1,2, K. Hirose3, K. Arai1, T. Motoyanagi1, T. Harada1, A. Takeuchi1, R. Kato1, H. Tanaka4, T. Mitsumoto5, Y. Takai3

1Southern Tohoku BNCT Research Center, Department of Radiation Physics and Technology, Koriyama, Japan, 2Fukushima Medical University, Preparing Section for New Faculty of Medical Science, Fukushima, Japan, 3Southern Tohoku BNCT Research Center, Department of Radiation Oncology, Koriyama, Japan, 4Institute for Integrated Radiation and Nuclear Science- Kyoto University, Department of Medical Physics, Kumatori, Japan, 5Sumitomo Heavy Industries Ltd., Department of Particle Accelerator, Tokyo, Japan

Purpose: To describe the design and construction of an accelerator-based boron neutron capture therapy (AB-BNCT) facility with multiple treatment rooms at the Southern Tohoku BNCT Research Center (STBRC).

Materials and Methods: AB-BNCT system at the STBRC is equipped with a cyclotron-based epithermal neutron source (C-BENS), which consists of a cyclotron accelerator (HM-30), a beryllium neutron production target, and a beam shaping assembly (BSA). We developed a remote patient transport system (RPTS) for workers to reduce the work time in the treatment room under the condition of remaining activities just after an irradiation. We studied the feasibility of this system and carefully designed optimum layout to realize patient flow and workflow efficiently.

Results: We designed the upside-down Y shaped beamline configuration, in which HM-30 and two treatment rooms are assumed to be located on a top and bottoms, respectively. To reduce the activities caused by thermal neutron, BSA is surrounded by LiF-loaded polyethylene blocks and low-activation concrete. The measured out-of-field thermal and fast neutron dose profiles were in good agreement with calculated ones using MCNPX. It was also confirmed that the RPTS could be operated up to 9 m apart from the RPTS without any problems.

Conclusion: We successfully established the environment of BNCT as one of a division of a general hospital without a sense of incongruity in comparison to an environment of conventional radiotherapy. The AB-BNCT system described in this study confirmed to specifications and is being used for BNCT in a hospital.

Physics: Absolute and Relative Dosimetry, PTC58-0203

GATE/Geant4 as a Monte Carlo simulation toolkit for light ion beam dosimetry

M. Bolsa-Ferruz1, H. Palmans1,2, A. Carlino1, M. Stock1, L. Grevillot1

1EBG MedAustron GmbH, Medical Physics, Wiener Neustadt, Austria, 2National Physical Laboratory, Radiation Dosimetry, Teddington, United Kingdom

Solid-state dosimeters are good candidates in light ion beam dosimetry due to the possibility of reducing the scoring volume down to sub-millimeter size. In contrary to ionization chambers, their relative effectiveness (RE) (i.e. energy and LET dependence correction) must be considered. The aim of this work is to determine the RE and the water-to-medium stopping power ratio (sw,med), which are necessary to derive dose to water from detector signal. For this purpose, the GATE/Geant4 Monte Carlo simulation platform [1] is used. Several detectors (alanine, films and optically stimulated luminescent detectors (OSLD)) are studied in clinical conditions. An analytical expression for the sw,med was determined as a function of the energy deposition scored by GATE/Geant4 and the water and medium mass stopping powers of the particle. A new tool for the computation of the RE was implemented in GATE. The capabilities of GATE for the determination of sw,med have been demonstrated. For alanine and aluminium oxide (Al2O3), the sw,med is varying by up to 2% and 10%, respectively, over the depth-dose profile. Currently, the dose distributions corrected by the sw,alanine and REalanine are being compared with those obtained with ionization chambers and alanine pellets (measurements acquired during medical commissioning of the proton beam line at MedAustron [2]). Subsequently, the validation of the sw,alanine and REalanine calculation for the carbon ion beam line will be performed during the second quarter of 2019. References: [1] Sarrut, D., et al.” Medical physics 41.6Part1 (2014). [2] Carlino, A., et al. Physics in Medicine & Biology 63.5 (2018):055001.


Energy dependence of LiF detectors in proton beam dosimetry

Y.S. Chen1, S.W. Wu1, H.C. Huang1, H.T. Wang1, C.Y. Yeh1, H.H. Chen1

1Chang Gung Memorial Hospital at Linkou, Proton and Radiation Therapy Center, Taoyuan, Taiwan

For patient dose monitoring purpose, the thermoluminescent detectors (TLDs) can easily report any interesting dose point as in-vivo dosimetry. However, the energy dependence may cause significant TLD measurement perturbation in proton beam dosimetry, especially for low energy beams. The purpose of this study is to evaluate the energy dependence on TLD measurement in protons.

Two types of TLD chips, TLD100 (LiF: Mg, Ti) and MCP100 (LiF: Mg, Cu, P) placed in HDPE phantom at 2 cm depth, were irradiated with 70-230 MeV of proton beams. The energy dependence was evaluated in terms of relative efficiency, which is the ratio of the emitted luminesce light intensity per unit dose for proton and 6 MV photon beam. The proton mean energy was calculated by GEANT4 Monte Carlo simulation code with various incident beam energies. The relation between the relative efficiency and proton mean energy can be established and used for energy dependence correction in proton beam dosimetry.

The measurement results from TLD100 and MCP100 were converted to relative efficiency. The relative efficiency of TLD100 and MCP100 in 70-230 MeV of proton beams ranged from 1.00 to 1.15 and 0.50 to 0.93, respectively. Accurate dose measurement using TLDs can be achieved by adopting appropriate relative efficiency correction, especially for different TLD types.


Development of a bone-equivalent material for the dosimetry of proton therapy beams

H. Cook1, G. Royle1, H. Palmans2, A. Lourenço2

1University College London, Medical Physics and Biomedical Engineering, London, United Kingdom, 2National Physical Laboratory, Radiation Physics, London, United Kingdom

Currently, tissue-equivalent materials have only been optimised for photons and electrons. Therefore, this research project has been proposed to develop tissue-equivalent materials that are suitable for proton therapy, so a uniform or anthropomorphic phantom can be created for the dosimetry of proton therapy beams.

So far four bone-equivalent materials, Hard cortical SB5, CIRS Cortical bone, Accura Bluestone and NPL bone material, have been compared to ICRP cortical bone at both 60 MeV and 200 MeV. Results have been calculated from an analytical model and FLUKA models which allow for the theoretical calculation of key dosimetric parameters; including mass stopping power, range, scattering length and fluence correction factors. SB5 and CIRS materials perform best out of the four materials. However, the results can have a 2-3% inaccuracy depending on what dosimetric parameter is being considered. Tissue-equivalent materials have been shown to be less tissue-equivalent at higher energies due to the increased difference in nuclear interactions.

The next stage of research is to test experimentally those currently available as well as newly developed materials against real bone samples with a proton therapy beam. Laterally integrated dose as a function of depth will be measured with ionization chambers in a water phantom. Gafchromic film (EBT3) will be used to investigate scattering properties. The test will obtain relative measurements of the bone-equivalent materials against cortical pig bone samples. These measurements will be compared to results collected via an analytical model and FLUKA model to determine the bone-equivalence of these materials.


Towards a synchrotron dedicated system for range control through Prompt Gamma Spectroscopy: Experimental results from p, He-4, C-12, O-16 beams

R. Dal Bello1,2, P. Magalhaes Martins1,3, G. Hermann4, T. Kihm4, M. Seimetz5, S. Brons6, J. Seco1,2

1German Cancer Research Center - DKFZ, Biomedical Physics in Radiation Oncology - E041, Heidelberg, Germany, 2University of Heidelberg, Department of Physics and Astronomy, Heidelberg, Germany, 3Instituto de Biofísica e Engenharia Biomédica - IBEB, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal, 4Max Planck Institute for Nuclear Physics, Heidelberg, Germany, 5Instituto de Instrumentación para Imagen Molecular - I3M, CSIC-Universitat Politècnica de València, València, Spain, 6Heidelberg Ion Beam Therapy Center - HIT, University Hospital Heidelberg, Heidelberg, Germany

Beam monitoring techniques aim to retrieve the position of the Bragg peak in the target in order to mitigate the planning limitations caused by the range uncertainties. This critical issue applies to all the beam species used in ion beam therapy. We propose the use of Prompt Gamma Spectroscopy (PGS) to provide on-line and in-vivo beam tracking for 1p, 4He, 12C and 16O beams. Our system includes a spectroscopic unit based on CeBr3 and BGO scintillating crystals, a scintillating fibres beam trigger and an advanced FADC/FPGA data acquisition system for high speed digitalization. The development of the system focusses on the application of PGS in synchrotron-based facilities. Such system is applicable not only to the clinical beam species (1p and 12C), but also to the ones in research phase (4He and 16O) . The preliminary results show excellent performances in the detection of the gamma radiation over the full energy spectrum for all beam species (Figure 1). We observed a significant widening of the spectral lines when increasing the mass of the projectile, which should be attributed to the Doppler broadening. Moreover, we measured a strong correlation of the residual range of the primary 12C particles with the intensities of the discrete reactions (Figure 2). Future work will include a complete characterization of the system and the systematic measurement of the energy dependent cross sections


2D radiophotoluminescence imaging for dosimetry of charged particle beams

M. De Saint-Hubert1, J. Swakon2, L. De Freitas Nascimento3

1Belgian Nuclear Research Center SCK-CEN, Unit Research in Dosimetric Applications, Mol, Belgium, 2Institute of Nuclear Physics Polish Academy of Sciences, CCB – Cyclotron Center Bronowice, Krakow, Poland, 3Belgian Nuclear Research Center SCK-CEN, Unit Research in Dosimetric Applications, Mol, Belgium

2D film dosimetry in charged particle therapy is important for mail auditing of proton therapy (PT) centers where 2D dose information is important to verify beam homogeneity and geometry and 2D imaging of the Bragg peak to check proton energy/range. Film dosimetry using the commercial gafchromic EBT3 films face challenges because of the density of ionizations i.e., linear energy transfer (LET), changes when penetrating through material. Luminescence materials have been studied as potential candidates for 2D dosimetry and radiophotoluminescence (RPL) detectors recently gained attention.

In SCK•CEN a stable 2D RPL dose scanning system was developed requiring limited corrections for image reconstruction, with a sub-millimeter spatial resolution (0.86 ± 0.10 mm). The Al2O3:C,Mg films demonstrated a dynamic dose response between 0.1 Gy and 100 Gy while the luminescence efficiency decreased as a function of high LET beams (1H, 4He, 12C, 28Si and 56Fe).

The feasibility of 2D Bragg curve imaging has been demonstrated for a 61.3 MeV 40 mm diameter broad proton beam using a wedged phantom [De Saint-Hubert et al, Radiation Measurements 2019]. Next an algorithm is implemented to correct for the film's luminescence efficiency dependence with improved 2D Bragg peak imaging for an accurate analysis of the beam parameters. RPL sheets are irradiated in different PT beams and phantoms (wedged and stacked) in combination with Monte Carlo simulations.

The objective of this work is to demonstrate the feasibility of 2D RPL films (Al2O3:C,Mg) for optimized 2D film dosimetry in charged particle beams and its application in PT auditing.


Theoretical study of physical parameters of fundamental importance in reference dosimetry for hadron therapy

V.B. Tessaro1, F. Poignant2, B. Gervais3, M. Beuve2, M.E. Galassi4

1Universidad Nacional de Rosario- Instituto de Física Rosario and Université de Lyon 1, FCEIA - Departamento de Física- Escuela de Cs. Básicas- Biomedical Physics Group and Institut de Physique Nucléaire de Lyon, Rosario, Argentina, 2Université de Lyon 1, Institut de Physique Nucléaire de Lyon, Villeurbanne, France, 3CEA/CNRS/ENSICAEN/Université de Caen-Basse Normandie UCBN, Center de Recherche sur les Ions- les Matériaux et la Photonique CIMAP/GANIL, Caen, France, 4Universidad Nacional de Rosario and Instituto de Física de Rosario, FCEIA - Departamento de Física- Escuela de Cs. Básicas. Biomedical Physics Group, Rosario, Argentina

The reference dosimetry in hadron therapy is based in the detection of secondary electrons generated by the ionization of the gas contained in ionization chambers. To determine the dose in liquid water, conversion factors such as W-values (mean energy expended by the incident particle to form an electron-hole pair after complete dissipation of its initial energy) in the gas of the ionization chamber are necessary. This physical parameter represents an important source of uncertainties in hadron therapy [1]. In a recent work [2] we studied the W-values by electron, proton and antiproton impact on vapor and liquid water. We used two different methods to take into account the slowing down of the primary particle and all the secondary electrons generated: the Monte Carlo code MDM (which does an event-by-event tracking of all particles, the primary and the secondary electrons) and the Fowler Equation (based in the Continuous Slowing Down Approximation). The results are in very good agreement with experimental data for water vapor and with values obtained by other authors for liquid water. In the present work, we calculate W-values by proton impact on the gases that compose the air extending the theoretical methods developed in [2]. Results obtained for proton energies from 0.5 to 100 MeV are in very good agreement with experimental data. In future work, these models will be extended to calculate W-values for other ions used in hadron therapy. References: 1) IAEA-TRS 398 (2005).

2) Tessaro, Poignant, Gervais, Beuve, Galassi. Nuclear Inst. and Methods in Physics Research B, (2018)


Disagreement of measured small-field output with treatment planning system for a Varian ProBeam system

J. Harms1, C.W. Chang1, R. Zhang1, Y. Lin1, K. Langen1, T. Liu1, M. McDonald1, L. Lin1

1Emory University, Department of Radiation Oncology and Winship Cancer Institute, Atlanta, USA

Purpose: For pencil-beam scanning protons systems, in-air non-Gaussian halo can significantly impact output at small field sizes and low energies. Since the halo is typically not modelled in treatment planning systems (TPS), this can potentially lead to significant differences in planned and delivered treatment. Here, we report the magnitude of such disagreements.

Methods: A CC04 small-volume ion chamber was used to measure absolute output from a ProBeam nozzle in water, and the results were validated with a diamond detector. Field sizes from 2-20 cm were employed with energies ranging from 70-240 MeV. Measurements were taken at the water surface and at half-range for each proton energy. Raystation 8A's clinical Monte Carlo algorithm was used for output modeling.

Results: The extent of the halo is shown in Fig. 1, where plots at Z300 show the spot size just after the protons leave the snout, and Z0 shows the spot size 300 mm downstream. Fig. 2 shows the output measurements exhibit a 4-5% disagreement with the TPS for the 2 cm field with 100 MeV, and an 8% disagreement in output for the 2 cm field with 70 MeV.

Conclusions: We found that the clinical TPS overestimated output by as much as 8% for small field sizes of 2 cm at extremely low energy of 70 MeV. The in-air halo of low energy extension to 2-3 cm diameter may potentially lead to underdosage of patients treated with small fields.


A high throughput method for in vitro proton cell irradiation

M. Howard1, J. Denbeigh1, N. Remmes1, E. Debrot2, M. Herman1, C. Beltran1

1Mayo Clinic, Radiation Oncology, Rochester, MN, USA, 2University of Wollongong, Center for Medical Radiation Physics, Wollongong, Australia

Background: Though proton therapy has become a well-established radiation modality, continued efforts are needed to improve our understanding of the molecular and cellular mechanisms during treatment. Such studies are challenging, requiring many resources. The purpose of this study was to create a phantom that would allow for multiple in-vitro experiments to be irradiated simultaneously with a spot scanning proton beam.

Methods: The setup utilized a modified patient couch top coupled with the robotic arm for submillimeter positioning. An acrylic phantom was created to hold four 6 well cell culture plates, at two different positions along the Bragg curve, in a reproducible manner. The proton treatment plan consisted of one large field encompassing all four plates with a monoenergetic 76.3 MeV posterior beam (fig. 1). For robust delivery, a mini pyramid filter was used to broaden the Bragg peak (BP) in the depth direction. EBT3 radiographic film was employed to validate absolute dose, using our in-house GPU-based Monte Carlo for LETd correction and provide secondary dosimetric evaluation.

Results: Due to beam divergence, variable proton path lengths in acrylic proximal to the cell plates resulted in film dosimetry ±1.4% for dose delivered across the length of each plate at the BP, with negligible difference in the entrance region.

Conclusion: The proposed proton irradiation setup allows for four plates to be simultaneously irradiated with two different portions (entrance and BP) of a 76.3 MeV beam. Dosimetric uncertainties across the setup are within + 2%.


The doses of scattered photon and neutron on cardiac implantable electronic devices in scanning proton therapy to right neck

Y.Y. Huang1, S.H. Tsai1, C.C. Sung1, F.M. Fang1, C.C. Huang1

1Kaohsiung Chang Gung Memorial Hospital, Radiation Oncology, Kaohsiung, Taiwan

Purpose: Patients with dependent cardiac implantable electronic devices (CIED) should avoid proton therapy to thorax due to high risk of malfunction resulted from secondary neutron production by proton beam. However, there was limited literature to evaluate the neutron dose on CIED in proton therapy for head and neck cancer. This study aimed to measure the doses of scattered photon and neutron on the surface site of CIED in scanning proton therapy to right neck.

Materials and Methods: A treatment planning of scanning proton therapy using right-anterior-oblique field and right-posterior-oblique field to treat right side head and neck cancer with 200cGy per fraction was adopted. On the bilateral infraclavicular surface areas of RANDO phantom, the Electronic Personal Dosimeters (DMC 3000 with Neutron Module) were set to simulate the ipsilateral and contralateral sites of CIED. We recorded the values of H10-gamma and H10-neutron detected by the dosimeters in proton therapy.

Results: The mean doses of H10-gamma and H10-neutron were 0.033 mSv and 0.530 mSv per fraction at left infraclavicular area and 0.024 mSv and 0.210 mSv per fraction at right infraclavicular area. Notably, both doses of scattered photon and neutron at left side were larger than those at right side despite the proton therapy to right neck.

Conclusion: The doses of scattered photon and neutron at bilateral infraclavicular areas were low; however, the doses at left side were unexpectedly larger than those at right side. The electrocardiogram monitoring during proton therapy and program analyzing after treatment should not be completely waived.


Reconstruction of physical and biological dose distributions of carbon-ion beam through deconvolution of longitudinal dosimeter responses

N. Kanematsu1, T. Inaniwa1, S. Yonai1, H. Mizuno1

1National Institute of Radiological Sciences, Department of Accelerator and Medical Physics, Chiba, Japan

Purpose: This is a theoretical simulation study for proof of concept of radiochromic film dosimetry to measure physical and biological doses without plan-based quenching correction for patient-specific quality assurance of carbon-ion radiotherapy.

Methods: We took a layer-stacking carbon-ion beam comprised of range-shifted beamlets. The dosimeter response was simulated according to an experimental quenching model. The beam model followed a treatment planning system. The beam was decomposed into finely arranged beamlets with weights estimated by deconvolution of longitudinal dosimeter responses. The distributions of physical and biological doses were reconstructed from the estimated weights and were compared with the plan. We also evaluated the sensitivity to measurement errors and to erratic delivery with an undelivered beamlet.

Results: The reconstructed physical and biological doses accurately reproduced the simulated delivery with errors approximately corresponding to the measurement errors. The erratic beam delivery was easily detectable by comparison of biological dose distribution to the plan.

Conclusions: We have developed a method to measure physical and biological doses by longitudinal dosimetry of quenched response without using plan data. The method only involves a general optimization algorithm, a radiobiology model, and experimental beamlet data, and requires no extra corrections. Theoretically, this approach is applicable to various dosimeters and to proton and ion beams of any delivery method, regardless of quenching or biological effectiveness.


Thermoluminescence sheet-type dosimeter for in vivo skin dosimetry in passive scattering proton therapy

T. Kato1,2, T. Sagara2, Y. Yamazaki2, M. Kato2, S. Oyama2, M. Murakami3

1Fukushima Medical University, Preparing Section for New Faculty of Medical Science, Fukushima City, Japan, 2Southern Tohoku Proton Therapy Center, Department of Radiation Physics and Technology, Koriyama, Japan, 3Southern Tohoku Proton Therapy Center, Department of Radiation Oncology, Koriyama, Japan

Purpose: Considering skin sparing is important in passive scattering proton therapy (PSPT), in which small number of fields may cause high entrance dose. In vivo skin dosimetry (IVSD) is desirable to perceive actual skin dose, however, the methodology of IVSD has not yet been established so far. Newly developed thermoluminescence sheet-type dosimeters (TLSD) are particularly suited for applications in IVSD because of their ease of use, and capability of adjusting size. We investigated the utility of TLSD for IVSD in PSPT.

Materials and Methods: Lithium triborate (effective atomic number 7.3) is the main component of TLSD (TOYO Medic Ltd., Tokyo, Japan). To evaluate the basic characteristics for proton beams such as dose linearity, uniformity, and energy dependences, unmodulated and modulated proton beams are irradiated to TLSD in parallel or perpendicular to the beam axis in the water phantom. Furthermore, to measure the actual range shift of the proton beam due to TLSD insertion in the field, the proton depth-dose curve measurements were obtained to determine water equivalent thickness (WET) with or without TLSD attached to the entrance wall of the water phantom.

Results: The dose response was found to be linear up to 10 Gy. The percent depth-dose and dose profile measured with TLSD well reproduced the results with ionization chamber. The WET without protective sheet was estimated to be approximately 0.2 mm.

Conclusion: Although there are some needs for improvement, the impact on range error is almost negligible in IVSD, new TLSD is suitable to be used as IVSD tools in PSPT.


Preparing for clinical translation of raster-scanning helium ion-beam therapy: Dosimetric validation with an anthropomorphic head phantom

S. Mein1, T. Tessonnier2, B. Kopp3, A. Mairani4

1German Cancer Research Center DKFZ, Translational Radiation Oncology, Heidelberg, Germany, 2Center François Baclesse, Radiation Oncology, Caen, France, 3University Hospital Heidelberg, Radiation Oncology, Heidelberg, Germany, 4Heidelberg Ion-Beam Therapy Center HIT, Radiation Oncology, Heidelberg, Germany

By 2020, the Heidelberg Ion Therapy Center (HIT) will launch the first clinical raster-scanning particle therapy program using helium ions (4He), which exhibit favorable physical and biophysical properties intermediate of the clinically used proton and carbon ion beams. To support clinical operations, development of the first treatment planning system (TPS) for 4He ions is currently underway. Recent works established a FLUKA Monte Carlo-based Treatment planning platform (MCTP) and an in-house GPU-based dose engine (FRoG) for the four ions available at HIT (1H, 4He, 12C and 16O). Preliminary validations compared spread-out Bragg peaks in water against measurements as well as patient dose calculations against gold-standard Monte Carlo simulations, demonstrating excellent agreement.

In this work, dose calculation and optimization performance is evaluated for 4He ion beams. Through rigorous dosimetric study in clinical-like and worst-case scenarios (using the CIRS Proton Therapy Dosimetry Head Model 731-HN and a RANDO Alderson half-head phantom, respectively), both 1D and 2D measurements are acquired with a 24 PinPoint ionization chamber block and an OCTAVIUS® 1000SRS prototype detector. Dose prediction performance using both analytical and Monte Carlo methods for 4Heion beams will be validated for the HIT clinic. Preliminary results (Fig. 1) demonstrate excellent agreement between FLUKA MC and FRoG against measurements, with absolute percent dose deviations 1.71(±1.09)% and 0.84(±0.61)% for FLUKA MC and FRoG, respectively.


Dosimetric comparison of techniques for left-sided breast and regional lymph node radiotherapy

C. Pembroke1, T. Joslin-Tan2, R. Maggs2, J. Lambert3, K. O'Neil3, P. Barrett-Lee1, J. Staffurth4

1Velindre Cancer Center, Clinical Oncology, Cardiff, United Kingdom, 2Velindre Cancer Center, Physics, Cardiff, United Kingdom, 3Rutherford Proton Partners, Physics, Newport, United Kingdom, 4Cardiff University, Radiation oncology, Cardiff, United Kingdom

Background: Irradiation of internal mammary (IMNI) nodal volumes have demonstrated significant survival gains in high-risk axillary node positive breast cancer. There are, however, concerns that increases in irradiated volumes may offset this benefit and optimal delivery solutions are being investigated.

Purpose: A dosimetric study for comparison of intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and spot scanning proton beam therapy (PBT) for patients receiving IMNI.

Method: Axillary (1–4) and IMN volumes were contoured as per ESTRO guidelines on 10 CT datasets in patients previously treated in deep inspiratory breath-hold (DIBH). IMRT (four-field), VMAT (two 200° arcs), and PBT (anterior and 'en-face' beams) plans were created with the aim to treat the breast (40Gy [100%]) and regional nodes (36Gy [90%]) in 15 fractions.

Results: VMAT and PBT plans met all mandatory objectives compared with only 7/9 IMRT plans. PBT plans had lower mean heart dose (0.6Gy ± 0.4 [1 SD]), left lung V17Gy (11% ± 1.6), and contralateral breast (0.1Gy ± 0.1) than IMRT (4.4Gy ± 0.6 / 30.9% ± 3.3 / 2.7Gy ± 0.5) and VMAT (4.1Gy ± 0.4 / 32.1% ± 1.4 / 3.2Gy ± 0.1) while achieving better coverage:

  • Breast PTV V38Gy: 99.1% ± 0.5 [PBT]; 94.1% ± 2.8 [IMRT]; 96.7% ± 1.7 [VMAT].

  • IMN PTV V36Gy: 99.6% ± 1.1 [PBT]; 93.2% ± 2.3 [IMRT]; 98.5% ± 1.6 [VMAT].

  • L1-L4 PTV V36Gy: 99.7% ± 0.6 [PBT]; 93.2 ± 3.2 [IMRT]; 98% ± 1.4 [VMAT].

Conclusion: This study demonstrates the dosimetric benefits of PBT over both photon modalities for IMNI. Further work investigating clinical correlation is necessary.


Does the relative effectiveness of Gafchromic EBT3 films in different proton beam qualities depend on the absorbed dose?

A. Resch1, P. Heyes1, D. Georg1, H. Palmans2, H. Fuchs1

1Medical University of Vienna, Radiotherapy, Vienna, Austria, 2MedAustron Ion Therapy Center, Medical Physics, Wiener Neustadt, Austria

Purpose: The response of Gafchromic EBT3 films depends on the beam quality of protons, often quantified by the dose average linear energy transfer (LETd). We experimentally investigated if this relative effectiveness (RE) is, in addition, dose dependent.

Material and Methods: RE was defined as the apparent film dose divided by the delivered dose and experimentally characterized in an SOBP ranging from 3.0 to 3.5cm in depth at different dose levels. To enlarge the LETd range, a low LET beam (nominal energy: 252.7MeV) was superimposed in two of the 1Gy iso-dose experiments (labeled ‘b2′ and ‘b3′). The delivered dose was simulated using GATE/Geant4 employing a validated beam model and normalized to measurements with a reference ionization chamber in the SOBP. Stacks of 5-6 films were placed in the center of a lateral 7x7cm2 field at different depths in water. Films were calibrated at low LETd, in the entrance plateau of a single-energy 179.2MeV proton beam.

Results: At a constant absorbed dose of 1Gy, RE decreased from 1.0 to 0.6 for LETd from 0.8 to 14keV/μm, respectively (Fig 1). Increasing the absorbed dose from 2 to 10Gy increased the RE by 20%, whereas this increase was almost negligible (±2%) from 0.5 to 2Gy, i.e., in the linear dose regime of the films.

Conclusions: The RE is a function of beam quality and the absorbed dose level. LET quenching decreases with increasing dose, particularly for high doses.


Effect of perturbation factors and I values using multicenter calibration factor data in reference dosimetry of ion beams

M. Sakama1, M. Hideyuki2, N. katsuhisa3, Y. Wataru3

1National Institute of Radiological Sciences, Medical Physics Section, Chiba, Japan, 2National Institute of Radiological Sciences, Radiation Quality Management Section, Chiba, Japan, 3Association for Nuclear Technology in Medicine, Dosimetry Calibration Center, Chiba, Japan

Currently, the calibration of ionization chambers for reference dosimetry is performed using cobalt 60 gamma rays, and the beam quality correction factors for the beam quality used by each user are used. Many data on the perturbation factors of various ionization chambers against cobalt 60 gamma rays have been reported using experiments and calculations, and new results have been reported due to the development of the Monte Carlo simulation. However, these results are not necessarily consistent due to differences in the Monte Carlo code and simulation system used. In recent years ICRU 90 reported new physical values such as I value and w value. Using the multicenter calibration factor data over the past 6 years by the Japanese secondary standard dosimetry laboratory, the perturbation factors with 10 types of cylindrical ionization chambers and 7 types of parallel plate ionization chambers were evaluated. Based on the results, the change of the absorbed dose was calculated including the influence of new I values by the ICRU 90. For the cylindrical ionization chambers the differences in the absorbed dose were close to IATA TRS 398 as a result, mainly due to the influence of new I values. For the parallel plate ionization chambers, the difference tended to be smaller than IAEA TRS 398 except for some ionization chamber mainly due to the evaluated perturbation factors against cobalt 60 gamma rays. To improve accuracy, further analysis and simulation should be required.


Microdosimetry with a 3D silicon on insulator (SOI) ‘mushroom’ detector in a low energy proton beamline for radiobiological experiments

A.T. Samnøy1, K.S. Ytre-Hauge1, M. Povoli2, A. Kok2, A. Summanwar2, T. Linh3, A. Rosenfeld3, E. Malinen4,5, D. Röhrich1

1University of Bergen, Physics and Technology, Bergen, Norway, 2SINTEF, Microsystems and Nanotechnology, Oslo, Norway, 3University of Wollongong, Center for Medical Radiation Physics, Wollongong, Australia, 4University of Oslo, Physics, Oslo, Norway, 5Oslo University Hospital, Department of Medical Physics, Oslo, Norway

Introduction: The relative biological effectiveness (RBE) of protons depends on the linear energy transfer or lineal energy. Measurements of lineal energy spectra are however rarely performed in conjunction with proton radiobiological experiments due to lack of suitable high spatial resolution microdosimeters. The aim of this study was therefore to apply a novel silicon based microdosimeter to measure microdosimetric spectra in a low energy proton beam used for radiobiological experiments.

Method: A 3D silicon on insulator (SOI) “mushroom” detector with a sensitive volume array was used in a 14.8 MeV proton beam line. The depth dose distribution and multiple lineal energy spectra were measured by sequential introduction of polyamide absorbers with 16 μm thickness. The depth dose measurements were compared to measurements with an Advanced Markus ionization chamber (IC; PTW Freiburg, Germany). The dose–mean lineal energy spectra were compared to Monte Carlo simulations (MC) performed with GATE.

Results: The measured depth dose distributions with the mushroom detector and the IC were in good agreement. The dose-mean lineal energies were in relatively good agreement with MC simulations, with an expected elevation towards the Bragg peak. The measured dose-mean lineal energy converted to tissue, y_D, ranged from 7 keV/ μm without absorbers to 18 keV/μm at the Bragg peak and to a maximum of 26 keV/μm at the distal dose fall-off region.

Conclusion: The obtained lineal energy spectra indicate that the novel 3D SOI “mushroom” detector can be used to characterize radiation quality of proton beams for radiobiological experiments with low energy protons.


PMMA and silica optical fiber response to 16.5 MeV proton beams

J. Asp1, A. Santos2, S. Afshar V.1, W.Q. Zhang1, E. Bezak3

1University of South Australia, School of Engineering, Adelaide, Australia, 2The University of Adelaide, School of Physical Sciences, Adelaide, Australia, 3University of South Australia, School of Health Science, Adelaide, Australia

Introduction: Recently, many reports have indicated optical fibres as ionisation quenching free detectors. The aim of this project is to develop a fiber-optic-based dosimetry system for proton beam monitoring. The system allows for small size dosimetry with a fast dose-rate measurement. In these initial experiments, the radioluminescence (RL) generated in optical fibres exposed to proton beam irradiation is investigated as a function of proton dose rate.

Methods: Two optical fibres were compared: poly methyl methacrylate (PMMA) and silica. An Ocean Optic spectrometer was used to analyse the optical spectrum emitted through the different optical fibres. Irradiations were performed using a 16.5 MeV proton beam (GE PETtrace cyclotron) with proton beam currents ranging from 0.1 nA to 120 nA.

Results: The optical spectra differed significantly between the two fibre types. PMMA emitted light at a wavelength of 450 nm, while the silica spectrum showed two peaks; one peak at 460 nm and one at 650 nm. In the case of PMMA, the emission spectrum was observed to significantly change as irradiation continued, shown to correlate with possible photodarkening within PMMA. For the silica fibres, the intensity of both peaks was observed to increase as irradiation continued, the ratio of the two peaks were observed to be proportional to the dose-rate.

Conclusion: Spectral changes were observed in PMMA and silica optical fibres when exposed to 16.5 MeV protons. In PMMA fibres, these changes were observed to be due to photodarkening. While the ratio in silica fibre peaks were dose-rate dependent.


Ion recombination and polarity correction factor for thimble and parallel plane type ionization chambers in proton pencil beam scanning

D. Shamurailatpam1, M. a1, G. k1, K. p1, N. mp1, R. t1, S. c2, R. j2

1Apollo Proton Cancer Center, Medical Physics, Chennai, India, 2Apollo Proton Cancer Center, Radiation Oncology, Chennai, India

Accurate determination of absorbed dose to water following IAEATRS-398 formalism demand prior knowledge of ionization chamber (IC) correction factors (CF). This study investigate ion recombination (Ks) and polarity (Kpol) CF for three types of ICs in proton pencil beam scanning (PBS), where the dose rate is much higher than conventional photon radiotherapy.

Ionization measurement from 10×10cm2 mono-energetic layer of proton energy 70.2-226.8MeV were carried out in water phantom at 2-8cm depths, using Roos-type parallel plate chamber (PPC05) and two thimble ICs (FC65PandCC13). Proton were delivered in continuous PBS mode from dedicated nozzle of an Isochronous-cyclotron based ProteusPlus. Ks were determined using two-voltage methods (150Vand300V), while Kpol were calculated from the ionization measured at ±300V.

As the energy increases from 70.2 to 226.8 MeV, value of Ks also increases (Figure1) from 1.0070-1.0280 for FC65P and 1.0034-1.0287 for CC13. For PPC05, Ks remains nearly constant with mean(SD) of 1.0016(0.0003). All chambers showed minimal effect on biasing voltage (Figure2) with mean(SD) Kpol at 1.0009(0.0009), 1.0005(0.0005) and 0.9998(0.0006) for FC65P, CC13 and PPC05 respectively. Ks and Kpol for FC65P IC measured at variable depths and fixed depth of 2cm resulted similar value with maximum deviation of ±0.588% and ±0.117%.

In conclusion, Ks varies largely with energy for thimble IC and if not accounted properly can contribute an absolute dose error of up to 2.5%. The polarity effect remains minimum for all ICs. PPC05 showed least Ks value, insensitive to proton energy and can be consider as reference detector for absolute dose measurement in water.


Developing film dosimetry to benchmark dose distributions in dynamically collimated pencil beam scanning proton therapy

B. Smith1, M. Pankuch2, C. Hammer1, D. Hyer3, L. DeWerd1, W. Culberson1

1University of Wisconsin-Madison- School of Medicine and Public Health, Medical Physics, Madison, WI, USA, 2Northwestern Medicine Chicago Proton Center, Medical Physics, Warrenville, IL, USA, 3University of Iowa, Radiation Oncology, Iowa City, IA, USA

Aim: GafchromicTM EBT3 film may serve as an excellent dosimeter to benchmark highly conformal dose distributions achieved using dynamic collimation in PBS proton therapy treatments. However, special consideration must be given to properly characterize the observed LET dependence of film. This work focuses on the development of novel methods to characterize the variability in the film's response that are specific to the conditions of an intended treatment field.

Methods: A set of SOBPs were delivered using the IBA UN beamline at the Northwestern Medicine Chicago Proton Center. A film calibration with a Co-60 source at the University of Wisconsin Accredited Dosimetry Laboratory was determined and used to convert net optical density change (netΔOD) to absorbed dose to water for this project. This response was characterized to the dose-averaged LET calculated at each measurement depth using a benchmarked Monte Carlo model.

Results: The changes in the film's SOBP response were linear with increasing LET and appeared independent over the range of netΔOD changes studied. This favors the assumption that a single, well-established calibration curve can be used with LET-based correction factors to account for film saturation.

Conclusion: The dose response characteristics and the associated uncertainty has been quantified for EBT3 film dosimetry for a variety of different clinical beam qualities. Its use in quantitative 2D dosimetry in high LET proton environments is promising. However, care must be taken to consider how the context of the film's measurement relates to its calibration as it can impact the overall measurement uncertainty.


Radiochromic films in charged particle beams

F. Van den Heuvel1, M. Brooke1, F. Fiorini1

1University of Oxford, Oncology, Oxford, United Kingdom

Radiochromic films have been shown to display under response to radiation containing higher–LET particles. The mechanism is thought to be the occurrence of multiple interactions within a sensitive volume of the film, which are then counted as a single interaction. While the effect can readily be measured and many groups have done so in the past a predictive algorithm allowing cross calibration in other modalities is lacking. This paper presents a theoretical treatment of the problem, provides a means to predict the amount of quenching for a given particle at a given energy. Finally, we present a comparison of measured quenching with our methodology. In earlier work from one of our group members the theoretical quenching was determined using a Monte Carlo simulation of an experiment where a stack of 26 EBT-3 films were irradiated using a SOBP treatment with 16 different energies. The quenching was measured by measuring the dose on each film and comparing this to the calculated value.


A new array detector for dose measurements in laser generated ultrashort proton beams used for radiobiology experiments

R. Vasilache1, M.A. Popovici2, M. Straticiuc3, L. Craciun4, C.E. Matei5, M. Radu6

1Canberra Packard SRL, Department of R&D, Bucharest, Romania, 2Bucharest Polytechnical University, Faculty of Applied Sciences, Bucharest, Romania, 3National Institute for Nuclear Physics and Engineering ‘Horia Hulubei'—IFIN-HH, Applied Nuclear Physics, Bucharest - Magurele, Romania, 4National Institute for Nuclear Physics and Engineering ‘Horia Hulubei'—IFIN-HH, Radioisotopes and Radiation Metrology, Bucharest - Magurele, Romania, 5National Institute for Lasers- Plasma and Radiation Physics- Bucharest, Lasers Department, Bucharest - Magurele, Romania, 6National Institute for Nuclear Physics and Engineering ‘Horia Hulubei'—IFIN-HH, Physics of Life, Bucharest, Romania

One of the research directions at the ELI-NP research infrastructure in Romania, using 10 PW lasers, is to provide more insight regarding the biological effectiveness of the proton beams. One major problem is the in-beam dosimetry for these experiments, not in the least due to the extreme shortness of the pulses. Due to the specifics of the laser pulse, the proton beams generated by laser acceleration have a length of only a few nanoseconds, which means that measurements with ion chambers will be affected by large recombination correction factors. Measuring those recombination factors through the usual method is not an option because the laser frequency is rather low (0.1 Hz is to be achieved) and, at least in the beginning, the pulses will not be highly repeatable). Therefore, we have developed an array of four chambers, each polarised at a different voltage. The chamber array is now being tested in various charged particle fields, and the present paper shows the results obtained in a 19 MeV proton beam from the TR19 cyclotron from NIPNE, Magurele. In order to determine the distance between the chambers, FLUKA simulations were used to calculate the reciprocal influences of the four chambers. The recombination correction factor was then determined in the 19 MeV beam, first by the classical method than using the array detector and the differences between the two are presented. We can safely conclude that the array can be used with good results for the dosimetry in ultrashort pulses of proton beams.


Prompt gamma-ray imaging for real-time in vivo range/dose verification in proton and carbon ion therapy

M. Xiao1, S. Paschalis1, P. Joshi1, T. Price2

1University of York, Department of Physics, York, United Kingdom, 2University of Birmingham, School of Physics and Astronomy, Birmingham, United Kingdom

In vivo range verification is desirable to understand the range uncertainties, minimizing beam delivery errors during hadron therapy. The aim of this project is to develop a novel prompt gamma-ray imaging (PGI) detector prototype for the absolute and relative range verification of hadron therapy, which can be used in clinical routine. Our group is dedicated to develop a novel PGI detector based on a group of scintillator crystals (Luteium Fine Silicate) that coupled with silicon photomultipliers (SiPMs), see picture1. A physical tungsten collimator will be applied for the PG profile along the depth of a PMMA/water phantom. In the meantime, the proton dosimetry can be estimated by a scintillator-fibre based microprobe, see picture2, that is inserted to the phantom. The measurements from both detectors will be used for the determination of the relationship between “Bragg peak” and PG peak. We have done the preliminary test of those detectors at university of Birmingham with proton beam at 36MeV and obtained the time-of-flight information and a fall-off profile with an 8ns timing window and a 3 - 4.5MeV energy window. There are two more experiments coming in the next couple of months in Birmingham and KVI, Netherlands (150MeV proton beam and 90MeV/n carbon ion beam). More results can be presented by that time. The final aim of range verification is dose verification, so Monte Carlo (MC) Geant4 simulation tool has be applied for our experimental setup and Machine learning method will be applied as we build our project database.


Dosimetric effects of a cranial Ti mesh for intensity modulated proton therapy

J. Yu1, A. Gutierrez1, M. Mehta1

1Miami Cancer Institute, Radiation Oncology, Miami, FL, USA

Purpose: Surgical titanium (Ti) meshes may be present in brain patients who receive intensity modulated proton therapy (IMPT). The purpose of this study is to quantify the dosimetric effects of a common Ti mesh.

Methods and Materials: IMPT plans were created in a solid water phantom with a Ti mesh(203mm, 203mm, 0.6mm) inserted at 0.5cm depth(Fig1). Two CTVs were located at 0.3 and 1.5cm depth below the mesh(Fig2). The TPS can take into account Ti by assigning material composition and density of Ti to the mesh. The IMPT plans were calculated with and without Ti override. Dose calculation grid and CT resolution were both 1mm. A multiple chamber array detector was used to measure the absolute 2-dimensional (2D) dose below the mesh at various depths from 0.6 to 6.7cm. Both pencil beam(PB) and Monte Carlo(MC) algorithms were used for dose calculation.

Results: For the calculated dose, the largest dose differences occurred downstream of the mesh at the distal edge of the target volume. The dose fall-off with Ti override was approximately 0.5 mm faster than the fall-off without Ti override. The differences between PB and MC were within 0.2 mm range. For the measured dose, the gamma (3%/3mm) passing rate was above 97%, and was within 2% difference for the absolute point dose.

Conclusion: Dose perturbation caused by the cranial Ti mesh for an enface beam appears small. The change of range caused by the mesh is within 1mm, which is the CT resolution and dose calculation grid limitation.

Physics: Absolute and Relative Dosimetry Poster Discussion Sessions, PTC58-0433

Range control through Prompt Gamma Spectroscopy with CeBr3 scintillators: Experimental evaluation of the spectroscopic unit in presence of He-4 beams

R. Dal Bello1,2, P. Magalhaes Martins1,3, J. Graça4, G. Hermann5, T. Kihm5, J. Seco1,2

1German Cancer Research Center - DKFZ, Biomedical Physics in Radiation Oncology - E041, Heidelberg, Germany, 2University of Heidelberg, Department of Physics and Astronomy, Heidelberg, Germany, 3Instituto de Biofísica e Engenharia Biomédica - IBEB, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal, 4German Cancer Research Center - DKFZ, Electronic Development Laboratory - E073, Heidelberg, Germany, 5Max Planck Institute for Nuclear Physics, Heidelberg, Germany

Ion beam therapy could offer superior dose distributions compared to conventional therapy. However, the high dose gradients make the plans sensible to uncertainties. Among the consequences, large tumor margins are applied and sub-optimal treatment angles are chosen. Prompt Gamma Spectroscopy (PGS) has been demonstrated as an online and in-vivo absolute range monitoring technique for proton beams. This is possible by correlating the intensities of the discrete spectral lines produced by the energy-dependent nuclear inelastic interactions with the residual range of the beam. Therefore, the efficient detection of the gamma spectrum is the fundamental requirement for PGS. In this work, we investigate PGS in presence of 4He beams at clinical relevant energies and intensities. We present the experimental evaluation of a spectroscopic unit based on CeBr3 scintillators, which combine high energy resolution, low intrinsic activity and accurate timing. The experimental setup includes an advanced FADC/FPGA based system for high-rate digitalization. The results show the capability of the system to detect efficiently the discrete reactions over the full energy spectrum (Figure 1). We observed excellent performances in the low energy component, which open the possibility to detect discrete lines unique to metal implants, e.g. titanium. Finally, a robust statistical analysis based on the F-Test determined whether a thin metal insert was placed in the beam direction. The introduction of secondary detectors for noise reduction relaxed significantly the statistic requirements. In such a case, we require a factor 2.5 less events to converge below the 1% significance level (Figure 2).


Hadron beam time tracker for time-of-flight measurements of prompt-gamma

P. Magalhaes Martins1,2, R. Dal Bello1,3, G. Hermann4, T. Kihm5, M. Seimetz6,7, J. Seco1,3

1German Cancer Research Center - DKFZ, Biomedical Physics in Radiation Oncology, Heidelberg, Germany, 2Institute of Biophysics and Biomedical Engineering - IBEB, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal, 3University of Heidelberg, Department of Physics, Heidelberg, Germany, 4Max Planck Institute for Nuclear Physics, n/a, Heidelberg, Germany, 5Max Planck Institute for Nuclear Physics, n/a, Heildelberg, Germany, 6Instituto de Instrumentación para Imagen Molecular I3M, Valencia, Spain, 7CSIC-Universitat Politècnica de València, n/a, Valencia, Spain

Prompt gamma imaging (PGI) is nowadays a well-established technique for range control in particle therapy. However, the arrival time information of the particles needed for PGI is still affected either by accelerator related proton bunch drifts against the radio frequency in cyclotron facilities or by the irregular time microstructure of ion beams extracted in synchrotron facilities. Several solutions have been proposed to circumvent this issue, e.g. bunch monitors or hodoscopes. None of them have been capable so far to