Overview

The theme for this year's conference was New Frontiers in Particle Therapy. Objectives for the 6th annual conference were to: Maintain best practices for proton therapy patient selection by recognizing maximum opportunity for toxicity reduction and/or tumor control probability improvement; appropriately identify patients for clinical trials and employ resources to overcome barriers to improve enrollment; determine where and when to implement advanced treatment planning approaches such as Monte Carlo, relative biological effectiveness (RBE), and linear energy transfer (LET); and consider limitations of proton therapy and recognize when applications of dual modality or non-proton therapy options are indicated to achieve optimal patient outcomes.

Target Audience

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

  • Radiation Oncologists

  • Medical Physicists

  • Dosimetrists

  • Residents

  • Radiation Therapists

PTCOG-NA Executive Committee

  • Eugen B. Hug, M.D., President

  • Hesham E. Gayar, M.D., Vice-President

  • Anita Mahajan, M.D., Secretary

  • Carl J. Rossi, M.D., Treasurer

PTCOG-NA Host Committee Members

  • Michael D. Chuong, M.D.

    Director, Clinical Research and Education, Miami Cancer Institute, Miami, Florida

  • Marcio Fagundes, M.D.

    Medical Director, Radiation Oncology, Miami Cancer Institute, Miami, Florida

  • Alonso N. Gutierrez, Ph.D., MBA

    Assistant Vice-President, Chief Physicist, Radiation Oncology, Miami Cancer Institute, Miami, Florida

  • Minesh P. Mehta, M.D.

    Deputy Director and Chief, Radiation Oncology, Miami Cancer Institute, Miami, Florida

PTCOG-NA Conference Planning Committee Members

  • Michael D. Chuong, M.D.

    Director, Clinical Research and Education, Miami Cancer Institute, Miami, Florida

  • Marcio Fagundes, M.D.

    Medical Director, Radiation Oncology, Miami Cancer Institute, Miami, Florida

  • Hesham E. Gayar, M.D.

    Medical Directort, McLaren Proton Therapy Center, Karmanos Cancer Institute, Flint, Michigan

  • Alonso N. Gutierrez, Ph.D., MBA

    Assistant Vice-President, Chief Physicist, Radiation Oncology, Miami Cancer Institute, Miami, Florida

  • William F. Hartsell, M.D., FACR, FACRO

    Medical Director, Chicago Proton Center, Radiation Oncologist, Northwestern Medicine, Chicago, Illinois

  • Eugen B. Hug, M.D.

    Professor, Radiation Oncology, Medical Director, MedAustron Ion Therapy Center, Wiener Neustadt, Austria

  • Anita Mahajan, M.D.

    Radiation Oncologist, Brain Tumor Program, Mayo Clinic, Rochester, Minnesota

  • Minesh P. Mehta, M.D.

    Deputy Director and Chief, Radiation Oncology, Miami Cancer Institute, Miami, Florida

  • Carl Rossi, M.D.

    Medical Director, California Protons Cancer Therapy Center, San Diego, California

BACKGROUND: Differences in proton and photon physics is an underlying reason for differences in biological effectiveness. Photons set in motion delta-electrons, which transfer energy to biological targets. According to Bethe-Bloch formula, an electron has the same LET as a proton travelling with the same velocity. This suggests that differences in energy spectra of electrons and protons are crucial for understanding differences in biological effectiveness. Electron spectra are complex and the term itself is prone to misinterpretation. We define the spectrum unambiguously as the probability distribution of energy of electrons entering a microscopic biological target.

METHODS AND MATERIALS: We account only for electrons that reach the target volume. In previous studies, average LETs were calculated using the source spectra, i.e. distributions of initial electron energies at the point of origin. These are not the spectra of electrons reaching the target. Electrons are mostly produced outside the target and lose some energy before they reach it. Using source spectra overestimates RBE variation with beam energy, NCRP 181. We calculate spectra of electrons entering microscopic volumes by solving an electron transport equation with Monte Carlo.

RESULTS: We report dose- and frequency averaged LETs for x-ray, brachytherapy, and gamma sources. For a 60Co source, our LETD is 4.6 keV/μm, an order of magnitude higher than reported previously, and higher than LET of protons with energies >10 MeV. The latter implies proton RBE<1 at higher energies. Our model (Vassiliev et al. Phys. Med. Biol. 2018) resolves this problem. It substantiates the use of LETF, which in our calculations is 0.40 keV/μm for 60Co.

CONCLUSIONS: We propose a definition of delta electron spectrum for radiobiological modelling and an algorithm for calculating it. We report average LETs for several sources. Our results are very different from those previously reported. They support using LETF instead of LETD.

BACKGROUND: Hypofractionated proton therapy with passive techniques for hepatocellular carcinoma (HCC) may have limitations when tumors are adjacent to organs-at-risk (OARs), which may result in tumor underdosage and lead to inferior local control. We present the first series of HCC patients treated with pencil beam scanning (PBS) intensity-modulated proton therapy (IMPT) using a simultaneous-integrated boost and protection (SIB/SIP) technique to escalate tumor dose while protecting adjacent OARs.

METHODS AND MATERIALS: Sixteen consecutive HCC patients were treated between 2015–2018 with a 15-fraction regimen using IMPT SIB/SIP. SIB/SIP dose levels generally ranged from 37.5 to 67.5 GyRBE to minimize dose to OARs at their respective dose-limiting thresholds (e.g. luminal gastrointestinal organs, chest wall). Hepatotoxicity was defined by a Child-Pugh (CP) score increase of 2 or greater and/or any RTOG grade 3 enzyme elevation. Other toxicities were graded by CTCAEv5.0. Overall survival and local-progression-free survival were calculated using the Kaplan-Meier method.

RESULTS: Patients most commonly had BCLC stage C (50%) and CP-A cirrhosis (71%). Median gross tumor volume (GTV) size was 12.7cm (599cc [228–1617]), and 38% had gross vascular invasion. Median GTV dosimetric parameters included: maximum prescription dose 67.5 GyRBE (60–67.5), mean 62.5 GyRBE (54.0–69.5), D1 68.0 GyRBE (61.6–71.3), and D99 50.4 GyRBE (33.4–67.7). Median liver-GTV parameters included: volume 1403.4cc (805–2130), mean 14.6 GyRBE (11.1–19.6), V30GyRBE of 27% (12%–35%), and V20GyRBE of 32% (21%–47%). At a median follow-up of 447 days (164–894) in alive patients, the median survival and 1-year overall survival was 22 months and 60%, respectively. Local control was 88% with no isolated local failures. Three patients experienced hepatotoxicity with no RILD-related deaths. No acute or late GI grade ≥2 occurred. One patient developed grade 3 chest wall toxicity.

CONCLUSION: In our series of HCC patients with large tumors near OARs, IMPT SIB/SIP results in excellent local control and acceptable toxicities.

BACKGROUND: While hypofractionated (Hypo) radiotherapy (RT) has widely replaced standard fractionated RT in the treatment of early-stage non-small cell lung cancer (NSCLC), major side effects have limited its use in advanced NSCLC. Based on the improved dosimetry of proton therapy (PT), we investigated the HypoPT approach for stage II–III NSCLC.

METHODS AND MATERIALS: Between March 2013 and November 2018, 28 patients from 4 centers were enrolled on a clinical trial of HypoPT with concurrent chemotherapy followed by adjuvant systemic therapy. Patients could be simultaneously enrolled in a phase 1 study and receive doses of 2.5 (n=14), 3 (n=6), 3.53(n=7), and 4 Gy/fraction (n=1) to a total dose of 60 GyRBE according to the open arm and organ-at-risk (OAR) dosimetric constraints. Patients had stage IIA (n=3), IIB (n=3), IIIA (n=15), and IIIB (n=7) NSCLC. CTCAE, v4.0, was used for toxicity assessment. The primary endpoint of the study was 1-year overall survival (OS). The study closed prematurely due to slow accrual.

RESULTS: The median follow-up for surviving patients was 23 months (range, 1–60). The 1- and 2-year OS rates were 89% and 66%, and the 1- and 2-year progression-free survival rates were 70% and 60%, respectively. Three patients died within 3 months of completing HypoPT: 1 from a bronchial hemorrhage; 1 from congestive heart failure following infectious pneumonia and C. Diff colitis; and 1 from paraneoplastic SIADH after completing just 42 Gy at 3.53 Gy/fraction. Additionally, 6 patients died more than 1 year after HypoPT: 5 from disease progression and 1 from a cardiac event.

CONCLUSIONS: In this phase I/II study, HypoPT at 2.5 to 3.53 Gy per fraction to a total 60 Gy (RBE) with concurrent chemotherapy was well tolerated with favorable PFS and OS. A large randomized clinical trial comparing HypoPT with standard fractionated RT or PT is warranted, especially in the setting of consolidation immunotherapy.

BACKGROUND: 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 and treatment; RC diagnosis and re-irradiation records; and toxicities. Outcomes, including overall Survival (OS) and Local Control (LC), were estimated using Kaplan-Meier.

RESULTS: Twenty-six patients (median follow-up 15.3 months) received proton PBSPT Re-RT from 2016–2018: 16 patients w/ recurrent RC [median prior dose 52.2 Gy (43.2–63.0)] and 10 patients w/ de novo RC and variable prior RT (9 for prostate, 1 for ovarian). Median Re-RT dose was 44.4 Gy [(16.0–60.0); 20/26 BID], and 22 received concurrent chemotherapy. Five 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 76.5% (95% CI 66.0–86.9%) and 77.7% (95% CI 68.8–86.6%), respectively.

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

BACKGROUND: Recent trends including proton therapy and reduced-dose cyclophosphamide have been adapted in head and neck rhabdomyosarcoma (HN-RMS) to reduce late morbidity. Our primary goal was to analyze local control and survival outcomes after photon versus proton irradiation in pediatric patients with HN-RMS, with the secondary goal of analyzing the effect of cyclophosphamide dose on disease outcomes.

METHODS AND MATERIALS: This was a cohort study comprising 76 pediatric patients treated with definitive chemoradiation for HN-RMS from 2000 to 2018. Fifty-one patients (67%) were treated with intensity-modulated photon radiation therapy (IMRT) and 25 patients (33%) were treated with proton therapy.

RESULTS: Local failure (LF) at 3 years was 21.8% for parameningeal RMS and 0% for orbital RMS and other head and neck sites (p=0.24). Patients who were treated with protons were more likely to have received reduced dose cyclophosphamide (p<0.0001). The 3-year LF was 10.0% in the IMRT cohort versus 21.6% in the proton cohort (p=0.07). Cyclophosphamide dose was associated with LF: the 3-year LF was 3.9% for patients who received a cumulative dose of >20g/m2 versus 18.4% for ≤20g/m2 (p=0.04). Among patients with parameningeal RMS (n=59), both the cumulative cyclophosphamide dose and dose-intensity were associated with local failure (p=0.01). There were no differences in survival outcomes among the IMRT and proton cohorts. There was a trend toward worse event-free survival in patients with parameningeal RMS who received reduced dose-intensity cyclophosphamide (46.1% versus 67.5%, p=0.11).

CONCLUSIONS: Longer follow-up is needed in the proton cohort, although it appears that the dose of cyclophosphamide, rather than radiation modality, is likely the factor affecting local disease control. Efforts focused on further evaluating the optimal dose of cyclophosphamide or alkylating agents needed to balance disease control with toxicity are needed.

BACKGROUND: Due to the excellent outcomes with image-guided stereotactic body radiotherapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC), and the low treatment-related toxicities using proton therapy, we investigated treatment outcomes and toxicities for delivering hypofractionated proton therapy (PT).

METHODS AND MATERIALS: Between 2009 and 2018, 22 patients with T1–T2N0M0 NSCLC (45% T1, 55% T2) were enrolled and treated with image-guided hypofractionated PT on an IRB-approved phase II clinical trial. The median age at diagnosis was 72 years (range, 58 – 90). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. Nine patients (41%) were treated with 48 GyRBE in 4 fractions for peripheral lesions, and 13 patients (59%) were treated with 60 GyRBE in 10 fractions for central lesions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks.

RESULTS: The median follow-up for all patients was 3.5 years (range, 0.2–8.8 years). The overall survival rates at 3 and 5 years were 81% and 49%, respectively. The cause-specific survival rates at 3 and 5 years were 100% and 75%, respectively. The 3-year local, regional, and distant control rates were 86%, 85%, and 95%, respectively. Four patients experienced in-field recurrences. The median time to local recurrence was 26.5 months (range, 19–47 months). One patient (5%) developed a late grade 3 bronchial stricture that required hospitalization and stent.

CONCLUSIONS: Image-guided hypofractionated PT for early-stage NSCLC provides promising local control and long-term survival with low toxicities. Regional nodal and distant relapses remain a problem.

BACKGROUND: To report clinical outcomes associated with post-prostatectomy PT. Toxicity outcomes for this cohort were recently published.

METHODS AND MATERIALS: The first 100 consecutive patients from 2010–2016 were retrospectively assessed. Biochemical failure (BF; 2 consecutive rises above the nadir), first site of clinical failure – local, regional, and/or distant metastasis (DM) – and overall survival were recorded from start of radiation. BF- and DM-free survival Kaplan-Meier curves were estimated. Cox proportion hazards model was used to assess uni- (UVA) and multivariable association (MVA) with BF; variables with <0.1 were included in the multivariable model.

RESULTS: Median age and months after surgery were respectively 64 years (range 42–77) and 25 (5–216). PT received was 70.2Gy (RBE) (89%), salvage (93%), prostate bed-only (80%), pencil beam scanning (86%), with intensity-modulated radiation therapy (31%), and with androgen deprivation (34%). Median follow-up was 55mo (16–80). BF was noted in 39 patients (39%). Median time to BF was 23mo (5–69). For patients with BF, local failure was eventually noted in 1 (1%) patient at 30mo. Regional pelvic nodal failure was noted in 4 patients (4%) – all treated to the prostate bed-only – at median 32mo (10–38), 2 of whom also had DM. DM occurred in 6 patients (6%) at median 30mo (10–41), 5 with bony and 1 with lung involvement. There was 1 death at 24mo, unrelated to prostate cancer. In summary, 4.5 yr BF free-, DM free-, and overall-survival were 61%, 94%, and 99%, respectively, in this single institution cohort treated primarily to the prostate bed only without androgen deprivation. On MVA, Gleason >7 (HR 3.55, 95% CI 1.83–6.88, p=0.000) and whole-pelvis with prostate bed PT (HR 0.28, 95% CI 0.10–0.79, p<0.016) were associated with BF.

CONCLUSIONS: Post-prostatectomy PT is feasible with comparable clinical outcomes to historical photon outcomes.

BACKGROUND: For most disease sites, level 1 evidence is lacking for proton beam therapy (PBT). By identifying target populations that would benefit most from PBT, prospective registries could overcome the challenges in clinical trials enrollment. Herein, we report clinical outcomes of patients treated with PBT for locally advanced non-small cell lung cancer (LA-NSCLC).

METHODS AND MATERIALS: Data were obtained from the multi-institutional prospective database of the Proton Collaborative Group (PCG). Inclusion criteria of our study were stage III LA-NSCLC, use of PBT, and availability of follow-up data. Survival time was calculated from the start of treatment until death or last follow-up. Kaplan-Meier curves were generated for groups of interest and compared with log-rank tests. Cox regression modeling was used to evaluate the relationship between selected covariates and overall survival (OS).

RESULTS: A total of 195 patients were included in the analysis. PBT alone was given to 93% of patients with a median equivalent dose in 2 Gy fractions (EQD2) of 63.8 Gy(RBE). Pencil beam scanning (PBS) was used in 20% of treatments. Treatment-related grade 3 adverse events (AEs) were rare: one pneumonitis, two dermatitis, and three esophagitis. No grade 4 events were reported. Two grade 5 events occurred, both cardiological, probably unrelated to PBT. The median follow-up time for living patients was 13.6 months and the median OS was 19.0 months. On multivariate analysis, good performance status (HR=0.26, 95% CI 0.15–0.47, p<0.0001), PBS use (HR=0.45, 95% CI 0.20–0.99, p=0.046), and increased EQD2 (HR=0.97, 95% CI 0.96–0.98, p<0.0001) were associated with decreased mortality.

CONCLUSION: PBT appears to yield low rates of AEs with encouraging OS for the treatment of LA-NSCLC. PBS use and increased EQD2 can potentially increase OS. Prospective databases such as the PCG registry could play a key role in the future but need meticulous updates to reflect the clinical reality.

PURPOSE: To evaluate treatment outcomes following definitive or adjuvant high-dose, image-guided proton therapy for patients with skull-base chordoma.

METHODS AND MATERIALS: Between February 2007 and February 2018, 91 patients with a median age of 53 years (range, 22–78 years) with a skull-base chordoma were treated with passively scattered 3D-conformal proton therapy to a median dose of 73.8 Gy(RBE) (range, 69.6–75.6 GyRBE) on a prospectively collected, IRB-approved outcomes tracking protocol.

RESULTS: The median age was 53 years (range, 22–78 years). Two patients received a component of intensity-modulated radiotherapy. Seventy percent (n=64) were men and 30% (n=27) were woman. Eighty-two percent (n=75) of patients had macroscopic disease at the time of radiotherapy; 18% (n=16) had undergone a macroscopic gross total resection. Overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. With a median follow-up of 3.7 years (range, 0.2–10 years), 26 patients experienced disease recurrence, including 26 local, 0 regional, and 1 distant recurrence. The median time to local progression was 2.2 years (range, 0.4–7.0 years). At the time of last follow-up, 66 patients were alive (56 with no evidence of disease progression) and 25 were deceased (18 with disease progression). There were no acute grade 3 toxicities related to the radiation therapy. The 4-year actuarial rates of overall survival, cause-specific survival, local control, and radiation therapy-related grade 3 toxicity-free survival were 83%, 87%, 76% and 83%, respectively.

CONCLUSION: Definitive or adjuvant high-dose passively scattered 3-dimensional conformal proton therapy for skull-base chordoma provides acceptable local control, comparing favorably to historic photon data, with no acute grade ≥3 radiation-related toxicity and an acceptable rate of grade ≥3 late toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

BACKGROUND: Post-prostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality-of-life with proton therapy.

METHODS AND MATERIALS: The first 101 consecutive patients treated with double-scattered proton therapy (DSPT) between 2006 and 2015 were retrospectively reviewed. Seventy-eight patients received DSPT to the prostate bed only. Twenty-three received a DSPT prostate-bed boost following prostate-bed and pelvic-node treatment (3 with conformal 3-dimensional radiotherapy; 20 with intensity-modulated radiotherapy). Ten adjuvant patients received a median dose of 66.6 GyRBE (range, 66.0–70.2). Ninety-one salvage patients received a median dose of 70.2 GyRBE (range, 66.0–78.0). Three patients had a single positive lymph node. Forty-seven patients received androgen deprivation therapy (ADT) for a median of 9 months (range, 1–30). Toxicities (CTCAE, v4.0) were prospectively graded, and patient-reported quality of life data were reviewed.

RESULTS: The median follow-up was 5.0 years (range, 0.8–11.3). Five-year biochemical relapse-free and distant metastases-free survival rates were 69% and 90% for adjuvant patients, 58% and 96% for salvage patients, and 58% and 95% overall. ADT was associated with improvement in biochemical relapse-free survival on univariate analysis (p=0.0286). Acute and late >grade 3 genitourinary toxicity rates were 1% and 6%. No patients had >grade 3 gastrointestinal toxicity. Acute and late grade 2 gastrointestinal toxicities were 5% and 2%. The median and range International Prostate Symptom Score, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 5 (range, 0–33), 7 (range, 2–25), and 100 (range, 42–100), 92 (range, 57–100), respectively at baseline, and 11 (range, 0–34), 5 (range, 4–24), 92 (range, 17–100) and 89 (range, 42–100) at the 5-year follow-up.

CONCLUSION: High-dose post-prostatectomy PT provides effective long-term biochemical control and freedom from metastasis, with low acute and long-term gastrointestinal and genitourinary toxicity.

BACKGROUND: Patients with esophageal or gastroesophageal junction (GEJ) cancers with isolated locoregional recurrences have limited definitive treatment options. Reirradiation with modest photon doses is associated with high toxicity rates. Proton therapy improves normal tissue sparing and may more safely allow reirradiation dose escalation. Outcomes and toxicities from the Proton Collaborative Group registry assessing proton reirradiation for esophageal/GEJ cancer locoregional recurrences are reported.

METHODS AND MATERIALS: This IRB-approved prospective, multi-institutional registry was queried for recurrent esophageal/GEJ cancer treated with a second course of radiotherapy using protons. Baseline demographics, treatment details, outcomes, and toxicities (CTCAEv4.0) were evaluated.

RESULTS: Twenty-five consecutive patients retreated from 7/2012–4/2018 were analyzed. Patients were a median of 70 years (52–82) and predominantly male (88%) and non-Hispanic Caucasian (88%) with adenocarcinoma (68%). Initial stage was: T1–4%, T2–8%, T3–76%, unknown–8%; N0–24%, N1–48%, N2–20%, unknown–8%; stage I–4%, IIA–4%, IIB–24%, IIIA–40%, IIIB–16%, IV–4%, unknown–4%. During their initial treatment (median 50.4/1.8Gy), all received concurrent chemotherapy, and five patients (20%) underwent resection. Median time to recurrence was 14.0 months (4.1–134.0). Proton reirradiation was delivered using uniform scanning or passive scattering (n=21) or pencil beam scanning (n=4) to a median 45.9Gy(RBE) (30.1–60.5) in 12–42 fractions. Eleven patients (44%) received concurrent chemotherapy. Median follow-up from reirradiation completion was 23.1 months among living patients. Fifteen patients died; 6/18-month survivals were 48%/24%. Only two patients (8%) developed locoregional recurrences (9.2 and 11.1 months following reirradiation) both salvaged with surgical resection. Grade 3 toxicities occurred in 20% (anemia=1; anorexia=2; dysphagia=2; esophagitis=2) and grade 2 in 44% (most commonly, fatigue=6). Grade ≥2 esophagitis and pneumonitis occurred in 16% and 0%, respectively. No esophageal fistula/stricture/necrosis and no grade 4–5 events occurred.

CONCLUSION: Proton reirradiation for locoregionally recurrent esophageal/GEJ cancers is feasible, achieves durable local control, and has relatively limited toxicity. Additional prospective investigations and analyses of cumulative dose constraints are warranted.

BACKGROUND: Proton partial breast irradiation (PBI) may decrease morbidity versus photon PBI by allowing superior normal tissue sparing. Single-institutional studies have reported feasibility of proton PBI but with conflicting toxicity results. We report 3-year outcomes of a prospective phase II trial investigating efficacy and toxicity of proton PBI.

METHODS AND MATERIALS: This multi-center Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women age ≥50 years with AJCC stage 0–2, node negative, ER-positive, ≤3cm, non-lobular invasive breast cancer or ductal carcinoma in situ who underwent breast- conserving surgery. Proton PBI was delivered to 40Gy(RBE) over 2 weeks. All received uniform scanning proton therapy except 1 receiving passively scattered protons; ≥2 treatment fields were used. Primary endpoint was progression- free survival. Adverse events were prospectively graded using CTCAEv4.0. BTCOS was used to assess patient-reported quality of life (PRQOL) endpoints and cosmesis (scored 1–4).

RESULTS: Thirty-eight evaluable patients (left-sided=21 [55%]) were enrolled between 2/2013–11/2016. Median tumor size was 0.95cm. Median age was 67 years (50–79). At a median follow-up of 35 months (12–62), all patients were alive, and no patient had local, locoregional or distant disease progression. One patient developed new ER-negative invasive ductal carcinoma of the contralateral breast. Twenty-nine patients (76.3%) received hormonal therapy. Seven grade 2 toxicities occurred (radiation dermatitis=1; lymphedema=1; hot flashes=3; dyspnea=1; fatigue=1). No grade ≥3 toxicities attributable to radiotherapy were observed. Five patients (13%) assigned a BTCOS score of 4 at 1- or 3-year follow-up. Median heart volume receiving 5Gy (V5Gy) was 0%; lung V20Gy was 0% and V10Gy 0.17%.

CONCLUSION: At 3 years, proton PBI provides 100% cancer control for early stage, ER-positive breast cancer with minimal toxicity and acceptable long-term PRQOL. These findings, together with excellent dosimetric sparing of critical organs achieved with proton PBI, provide evidence that protons are safe and effective for PBI.

INTRODUCTION: The treatment of targets with considerable motion is a big challenge in proton therapy, especially for pencil beam scanning (PBS) technique. The interplay effect can be significant particularly for small target treated with hypofractionation or SBRT. Deep inspiration breath hold (DIBH) can't apply to all patients, especially for lung patients with poor lung function. Here we present two SBRT lung cases treated with breath hold at the end of exhale (EoE) using PBS proton therapy.

METHODS AND MATERIALS: Two patients prescribed to receive SBRT lung treatment of 55 Gy in 5 fractions show target motion more than 1.5 cm on their 4DCT images. Both patients could not tolerate DIBH. Repeated CT scans were performed with patient holding their breath at EoE using Anzai respiratory gating system. A 4D movie was created from these BH scans to check the BH reproducibility. An average BH scan was used as the planning CT. Robust optimization was used on all BH scans with 4% range uncertainty and 5 mm setup uncertainty. Layer repainting and volumetric repainting were also used to minimize interplay effects.

RESULTS: Both patients tolerated BH well at EoE. Daily CBCT and verification CT (VFCT) showed good reproducibility of the target location. The average BH duration was around 15 seconds and patient could quickly resume the BH after resting two or three regular breaths. The clinic plan was forward calculated on the VFCT and both target and OAR DVHs remained similar to the nominal plan.

CONCLUSIONS: BH at EoE is a viable option for patient who can't tolerate DIBH, which reduces target motion and mitigate the interplay effect of PBS treatment. Multiple factors should be considered carefully when implementing this technique in clinic, for example, gating system selection, BH reproducibility, image verification during treatment, treatment plan robustness, and beam delivery time etc.

BACKGROUND: Proton therapy may increase the tolerability/effectiveness of concurrent chemo-radiotherapy for locally advanced cancers but is unproven and generally not covered by private insurers. There is very little data on the comparative effectiveness of proton vs. photon chemo-radiotherapy among private insurance patients to guide payers on coverage policies for protons.

METHODS AND MATERIALS: We conducted a comparative effectiveness study of adult non-metastatic cancer patients with non-Medicare private insurance treated with curative-intent proton chemo-radiotherapy vs. photon chemo-radiotherapy from 2011–2016 at Penn. The choice of radiation modality was largely determined by the insurer's proton coverage policy. Data on adverse events (AEs) and survival were gathered prospectively using standardized templates. Primary endpoint was 90-day AEs associated with unplanned hospitalizations (CTCAEv4 grade ≥3 AEs). Secondary endpoints included 90-day grade ≥2 AEs, decline in ECOG performance status during treatment, disease-free survival (DFS), and overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were used for adverse event outcomes and weighted Cox proportional hazards models were used for survival outcomes. Propensity scores were estimated using an ensemble machine-learning approach.

RESULTS: 920 patients were included (178 proton/742 photon). Median age was 57. Disease sites included H&N(25 proton/296 photon); CNS(44/128); lung(41/120), upper GI(34/78), and lower GI/GYN(34/120). Race, Charlson-Deyo comorbidity score, BMI, baseline toxicity, and baseline performance status were similar (p>0.05 for all). In propensity score weighted-analyses, proton chemo-radiotherapy was associated with significantly lower relative risk (RR) of 90-day grade ≥3 AEs (RR 0.51, 95%CI 0.32–0.81, p<0.01) and 90-day grade ≥2 AE's (RR 0.91, 95%CI 0.83–0.99, p=0.03). Decline in performance status (RR 0.85, 95%CI 0.70–1.04, p=0.11) and adjusted DFS and OS all favored proton therapy, but the differences were not statistically significant.

CONCLUSIONS In adults with locally advanced cancer who have private insurance, proton chemo-radiotherapy was associated with significantly reduced acute adverse events causing unplanned hospitalizations, with similar DFS and OS.

BACKGROUND: Definitive chemoradiation (CRT) for anal squamous cell carcinoma (SCC) is curative for most patients. Despite the high conformality of x-ray therapy most patients experience at least grade 2 (G2) acute toxicity as demonstrated in RTOG 0529. Proton beam therapy (PBT) offers significant dosimetric sparing of normal organs in lower dose ranges that may reduce toxicity although there is a lack of published clinical outcomes.

METHODS AND MATERIALS: We retrospectively compared acute toxicity outcomes of patients treated with CRT using protons or x-rays at our institution. Acute toxicity was evaluated per CTCAE version 4.0 criteria and was defined as during or within 90 days of PBT completion. Hematologic toxicity was not evaluable.

RESULTS: Fifty-one non-metastatic anal SCC patients received protons (n=12) or x-rays (n=39). PBT patients were older (median 69 vs. 62 years), more often female (91.7 vs. 76.9%), had more advanced T stage (T3–4: 50 vs. 18%) and less advanced N stage (N1–3: 16.7 vs. 28.2%). Median dose was similar (52.2 vs. 50.4 Gy) as was use of concurrent 5-fluorouracil/mitomycin-C (83.3 vs. 87.2%). PBT was delivered with pencil beam scanning in the supine position for all proton and 48.7% of x-ray patients. Median follow-up was 1.7 months (proton) versus 5 months (x-ray) from start of CRT. The incidence of acute G2 toxicities in proton versus x-ray patients was: GI (16.7% vs. 28.2%); GU (2.6% vs. 12.8%), skin (50% vs. 66.7%), proctitis (50% vs 51.3%). The incidence of acute G3 toxicities in proton versus x-ray cohorts was: GI (0% vs. 2.6%); GU (both 0%), skin (8.3% vs. 7.7%), proctitis (0% vs. 7.7%).

CONCLUSION: Our acute toxicity outcomes with both protons and x-rays are favorable compared to RTOG 0529. Future studies should prospectively evaluate whether PBT leads to clinically significant differences particularly for GI, hematologic, and sexual dysfunction toxicities.

BACKGROUND: Hodgkin lymphoma (HL) is the most commonly diagnosed adolescent cancer; with survival rates exceeding 95%, attention has turned to minimizing long-term morbidity and mortality associated with chemotherapy and radiation treatment (RT). Secondary malignancy (SM) and cardiovascular disease exceed population norms as the leading causes of death in long-term HL survivors, and breast cancer risk increases in a radiation dose-dependent manner. In contrast to photons, protons lack an exit dose, therefore decreasing the volume of heart, lungs, and breasts exposed to RT; this reduction is expected to decrease late toxicities and SM.

METHODS AND MATERIALS: Between 2012–2018, 49 HL patients were treated with protons via passive scatter or pencil beam scanning techniques on an institutional review board-approved outcomes monitoring protocol. Relapse free (RFS) and overall survival (OS) were calculated using Kaplan Meier.

RESULTS: Median age at treatment was 16 years (range 11–21); 61% were female. Fifty-five percent were high risk per AHOD1331; 35%intermediate, 6% favorable, and 4% relapsed/refractory. Most patients were treated according to Children's Oncology Group protocols: AHOD0331 (n=20), AHOD0831 (n=3), or AHOD1331 (n=12). Median dose was 21.6Gy RBE (range 21–36) to the mediastinum (n=46), neck (n=34), axilla (n=5), spleen (n=4), abdomen (n=4), and bone metastases (n=2). Median ipsilateral mean breast dose was 0.51Gy; heart mean dose was 4.51Gy; ipsilateral lung V20 was 8.6%. RFS was 90% and 85% at 2 and 4 years, respectively; OS was 100%. Five patients recurred at a median of 9 months post-treatment (range 3–25) in and out of the field. There were no marginal recurrences. Median clinical follow-up was 24 months. No SMs were reported. Four patients (8%) had transient grades 1–3 toxicities potentially related to RT.

CONCLUSION: Proton treatment resulted in favorable RFS, OS, and low doses to the heart, lungs, and breasts in a pediatric HL population, with low rates of acute and late toxicity.

PURPOSE: This study reports 10-year outcomes on 3 image-guided proton therapy (IGPT) trials for prostate cancer.

METHODS AND MATERIALS: Ten-year outcomes were assessed for 3 prospective trials of IGPT including 89 low-risk (LR), 82 intermediate-risk (IR), and 40 high-risk (HR) patients. Median ages for LR, IR, HR were 64, 68, and 72 years (range, 40–88). Treatment was 78–82 cobalt gray equivalent (CGE) in 39–41 fractions; HR patients also received weekly docetaxel (20 mg/m2) during IGPT and 6 months of androgen deprivation therapy. CTCAE, v4.0, was used for toxicity scoring and the International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) for patient-reported outcomes. Cumulative incidences were calculated for freedom from biochemical progression (FFBP) and toxicity rates with Kaplan-Meier estimates in parentheses for FFBP. EPIC domain score changes considered significant were 4–6 (bowel); 5–7 (urinary irritative/obstructive); 6–9 (urinary incontinence); 10–12 (sexual).

RESULTS: Median follow-up was 11 years. Ten-year FFBP rates for LR, IR, and HR were 96% (96), 93% (91), and 64% (58), respectively. Twenty-five patients had progression at a median time of 9.9. 7.2, and 4.0 years for LR, IR, and HR. With PSA progression, 3 also had local, 4 had nodal, and 6 had distant progression. Eleven of 14 HR patients with progression would now be classified as NCCN “very high risk.” The rate of 10-year grade ≥3 gastrointestinal and urologic toxicity incidences were 0.7% and 4.8%, respectively. Median pretreatment and >8-year IPSS scores were 8 and 6 for LR and IR and 9 and 10 for HR. There were no significant changes in EPIC bowel, urinary irritative/obstructive, and urinary incontinence scores at >8 years compared to baseline.

CONCLUSION: Ten-year clinical outcomes with IGPT remain excellent. Local progression was rare. Most progression occurred in “very high risk” patients. Long-term (>5-year) follow-up is necessary for outcome assessment.

BACKGROUND: Neurocognitive sequelae are well-recognized late toxicities of radiotherapy in children. In this prospective study, we assessed the effects of proton therapy on cognitive function over time in pediatric patients treated for primary central nervous system malignancies with the hypothesis that higher radiation dose to the brain would be associated with impaired cognition.

METHODS AND MATERIALS: Between 2014–19, 26 patients ages 4–21 were enrolled in this prospective trial. Patients completed neurocognitive testing using the National Institutes of Health Toolbox Cognitive Battery (TCB), a novel, validated, computer-based assessment analyzing cognitive function along seven unique domains. Testing was completed at baseline and at annual follow-up visits following completion of radiotherapy. Linear mixed effects models were used to analyze the effects of age, time since treatment, total dose, dose to critical organs at risk, and socioeconomic status on TCB metrics with significant cognitive dysfunction (SCD) defined as a decline in score of >1 standard deviation during follow up.

RESULTS: Of the 26 patients enrolled, 14 received craniospinal irradiation, and 12 were treated with involved-field radiotherapy. Median follow-up was 24 months (range:12–36 months), and at last follow-up median scores declined in overall cognitive function (96.8 v. 92.0, p=0.02) as well as executive functioning (95.8 v. 83.5, p=0.005) and working memory (105.5 v. 96.0, p=0.008) domains. Higher poverty level was associated with greater declines in executive functioning (p=0.03), but no other associations were seen with sociodemographic factors. On dosimetric analysis, brain V50 was most strongly associated with decreased overall cognitive function score (p=0.01), and patients with brain V50 >10% had a higher-odds (OR=6.38, 95% confidence interval: 1.03 – 51.78, p=0.048) of SCD.

CONCLUSIONS: In this study, higher doses of radiotherapy were associated with greater declines in neurocognitive function. By reducing integral dose, proton therapy may help mitigate these sequelae

BACKGROUND: Hyperthermia (HT) has been regularly used as an excellent radiosensitizer with conventional radiotherapy (RT). There is a paucity of safety/efficacy data for the concurrent use of proton therapy (PT) and HT due to the lack of institutions with capabilities for both modalities. We report, herein, the largest, and growing, clinical experience with concurrent Pencil Beam Scanning Proton Therapy (PBS-PT) and HT to date.

METHODS AND MATERIALS: At our institution, PBS-PT has been utilized in over 1,400 patients, of which 30 courses/sites (25 curative, 5 palliative) have been delivered with concurrent superficial-HT in 27 patients. Histologies include sarcoma (n=11), breast (n=9), vulvar (n=1), skin (n=1), mesothelioma (n=1), ovarian (n=1), head/neck (n=1), anal (n=1), and ureteral (n=1) cancers. PBS-PT doses ranged from 36 to 70.2 Gy(RBE) (median 57 Gy[RBE]) including altered/hypo-fractionation. The BSD-500 platform was utilized for all superficial-HT administrations (median 8, range 4–28 HT sessions per course).

RESULTS: With a median follow-up of 7.4 months (range 1–31 months), concurrent superficial-HT and PBS-PT has been well tolerated. There were no acute/subacute grade 4–5 toxicities. Grade 3 toxicity arose in only 5 patients: acute desquamation (n=3), chronic lymphedema (n=2). Grade 1–2 toxicities included radiation dermatitis, pain, hyperpigmentation, and GI disturbance. Twenty-two patients (81.4%) remain alive, while 20 (74.1%) are locally controlled and 18 (66.7%) remain free of disease.

CONCLUSION: Concurrent PBS-PT and superficial-HT is well tolerated. While long-term follow-up and prospective data are needed, superficial-HT has represented a safe adjunct to particle therapy in the largest institutional experience to date with this combination.

*Previously submitted in similar form to the 2019 PTCOG58.

BACKGROUND: Proton Radiography (P-Rad) images provide information on the patient's position within the beam path in addition to the proton water equivalent pathlengths through the patient. A P-Rad can therefore be used for patient alignment as well as a pre-treatment range consistency check. A quantification of the sensitivity of these parameters was performed for a prototype P-Rad system.

METHODS AND MATERIALS: To quantify the alignment accuracy, Monte Carlo simulated P-Rad images of a brain tumor patient were created from CT image sets offset from a nominal position with known translations and rotations. Single proton positions and the residual energy were scored in the P-Rad detectors and processed through an iterative most likely path back-projection algorithm. To quantify the sensitivity to pathlengths changes, actual P-Rad images were acquired of a pediatric head phantom with a 2cm square cavity in the center. Various inserts of known WET were placed in the cavity and compared to the known thickness of the inserts.

RESULTS: Patient alignment results show that the P-Rad images could be used to obtain a positional correction vector in the Lt/Rt, Ant/Post and Sup/Inf directions by an average of 0.0mm, 0.0mm and −0.1mm with a standard deviation of 0.4mm, 0.4mm and 0.3mm respectively. Average angular accuracy in the Yaw, Pitch and Roll directions were −0.1deg, 0.1deg and 0.1deg with a standard deviation of 0.2deg, 0.2deg and 0.5deg respectively. WET consistency results of actual P-Rad images of a head phantom were able to detect pathlengths differences as small as 0.5mm with statistical certainty.

CONCLUSION: P-Rad images in the head region can be used to correct for positional offsets and quantify pre-treatment pathlengths consistency.

OBJECTIVE: To report demographic and clinical characteristics of patients who were more likely to receive proton beam therapy (PBT) than photon therapy from facilities with access to proton centers.

METHODS: We utilized the national cancer database to identify the facilities with access to PBT between 2004 – 2015 and compared the relative usage photons and PBT for demographic and clinical scenarios in breast, prostate, and lung cancer.

RESULTS: In total, 231 facilities with access to proton centers accounted for 16,8323 breast, 39,975 lung, and 77,297 prostate cancer patients treated definitively. PBT was used in 0.5%, 1.5%, and 8.9% of breast, lung, and prostate cases. PBT correlated with a farther distance traveled and longer start time from diagnosis for each site (p<0.05). For breast, demographic correlates of PBT were treatment in the west coast (OR=4.8), age <60 (OR=1.25), white race (OR=1.94), and metropolitan area (OR=2.8). Left sided cancers (OR=1.28), T1 (OR=1.28), N2 (OR=1.71), non-ER+/PR+/Her2Neu- cancers (OR=1.24), accelerated partial breast irradiation (OR=1.98), and hypofractionation (OR=2.35) were predictors of PBT. For lung, demographic correlates of PBT were treatment in the southwest (OR=2.6), metropolitan area (OR=1.72), and Medicare insurance (OR=1.64). Higher comorbid score (OR=1.36), later year treated (OR=3.16), and hypofractionation (not SBRT) (OR=3.7) were predictors of PBT. For prostate, correlates of PBT were treatment in the west coast (OR=2.48), age <70 (OR=1.19), white race (OR=1.41), metropolitan area (OR=1.25), higher income/education (OR=1.25), and treatment at an academic center (OR=33.94). Lower comorbidity score (OR=1.42), later year treated (OR=1.84), low risk disease (OR=1.45), definitive compared to postoperative (OR=6.10), and conventional fractionation (OR=1.64) were predictors of PBT.

CONCLUSION: Even for facilities with established referrals to proton centers, PBT utilization is low, and socio-economic status may be a factor. PBT was more often used with left-sided breast and low-risk prostate cancers, without a clear clinical pattern in lung cancer.

BACKGROUND: Proton beam dosimetry enables far greater sparing of the lungs and heart than possible using photon beams but their use may be limited by skin toxicity if this is not carefully considered. This study investigated skin dose when undergoing chest wall radiotherapy with either photon or pencil beam scanning proton therapy (PBS-PT). Optimization methods in the setting of PBS-PT were used to better match skin doses encountered in photon chest wall irradiations.

METHODS AND MATERIALS: Calibrated film (in-house) and TLD flat packs from the Radiation Dosimetry Services at the MDACC were used on a CIRS phantom in the treatment geometry. Plans were developed using the RayStation TPS for both modalities. The PBS-PT plan used two enface beams with gradient matching to encompass the large field while the photon plan utilized a pair of tangential beams. Skin optimization was accomplished mainly by using a variable minimum radiological depth requirement for the Bragg peaks and evaluated using a skin contour.

RESULTS: Delivery consisting of 28 fractions of a 6 MV beam with 5 mm of bolus every other day resulted in 76% of the prescription dose at the skin as measured by TLDs. PBS-PT plans delivered 91% and 97% of the prescription dose for the skin- and non-optimized plans, respectively when measured by TLDs.

CONCLUSIONS: The dose to the skin during traditional photon chest wall radiotherapy is not 100% of the prescription and therefore such a requirement of proton plans might not be appropriate. Surface dose may be considered in order to achieve acceptable erythema and better cosmesis.

BACKGROUND: In situations, where the high density implant can't be avoided, it is critical to identify its relative stopping power (RSP) before proton beam planning. Herein, we proposed a clinical workflow to estimate the RSP of the high density implants and incorporating it into the clinical practice.

METHODS AND MATERIALS: The RSP of a hip implant system (DePuy CeramaxTM) was investigated as well as several high density materials (Titanium, Tungsten, Platinum, and Al2O3). To estimate the RSP, we use: (1) the software package Stopping and Range of Ions in Matter (SRIM; www.srim.org) (2) the National Institute of Standards and Technology (NIST) online program PSTAR (https://physics.nist.gov) and (3) If a sample implant was available, the RSP was measured. The data calculated by SRIM must be verified by at least either (2), (3), or using both, before using it in clinical plans. During the entire treatment course, the implant location is closely monitored via daily CBCT. If any change was noted, the physician was informed to review the dosimetric effect and to decide whether a re-plan was needed.

RESULTS: The RSP of the Titanium alloy stem and Ceramic cap of the hip implant system was calculated using SRIM. The result was less than 0.8% from the measured value (3.22 vs. 3.22 for the stem, 3.43 vs. 3.46 for the cap). The RSPs of other materials (Titanium, Tungsten, Platinum, and Al2O3) encountered in our clinic were estimated using SRIM and verified by PSTAR, and their discrepancies were within 1%.

CONCLUSION: The proposed clinical workflow is practically achievable, and clinically useful. This is especially important when the high density implant lie inside the target volume and therefore directing beams through target volume could be favored due to improved target volume coverage, plan complexity and robustness.

BACKGROUND: Uncertainty in proton relative biological effectiveness (RBE) may be a cause of radiation-induced normal tissue toxicity. Within late responding tissues such as the spinal cord, risk of radiation necrosis and paralysis resulting from changes in dose delivery and biological effect are of particular concern. Quantification of proton RBE is complex, as this dynamic value is dependent upon many experimental parameters, including linear energy transfer (LET), fractionation scheme and biological endpoint. The purpose of this study was to investigate the dependence of RBE on dose and on position along the Bragg curve in a living mouse spinal cord model.

METHODS AND MATERIALS: Cervical spinal cords of female, 8 week old C57BL/6J mice were irradiated (20–80 Gy; lateral opposed beams) at low-LET (entrance) or high-LET (Bragg peak) positions along the proton curve. Animals were anesthetized and restrained in a custom fabricated set up for treatment. Endpoint was defined as onset of radiation induced myelopathy, while weight and general health changes were recorded weekly. Rotarod tests were used to evaluate motor function on a bi-weekly basis. RBE will be calculated as the ratio of the tolerance dose at 50% effect probability (grade II paresis) upon completion of the study (300 days post irradiation).

RESULTS: Acute toxicities of temporary weight loss and skin abrasions were observed in both cohorts of mice. Forelimb paralysis was manifest in the highest dose groups and accompanied by performance deficits on the rotarod. Preliminary results suggest BP treated mice exhibit a shorter latency time to paralysis.

CONCLUSIONS: Robust characterization of proton RBE in our in vivo spinal cord model is crucial for informing clinical treatment strategies that strive to account for the biological variability of proton therapy in order to reduce short- and long-term side effects to critical organs.

BACKGROUND: Real time treatment is when the patient is imaged, planned and then treated while the patient is not moved from the treatment couch. One of the obstacles to implementation is quality assurance. While the treatment plan may be compared to an independent dose calculation before treatment to verify that the plan is of high quality, there is a challenge to confirm that the treatment machine will properly deliver the plan before treating the patient without actually treating the plan on the machine. Mayo Clinic Rochester, in cooperation with Hitachi Ltd., has developed a Real Time Patient Specific Quality Assurance process (RT PSQA) to mitigate this challenge.

METHODS AND MATERIALS: The workflow for Real Time PSQA is the same workflow as any new plan, except that the DICOM file of the treatment plan is transferred to a QA computer at the time of the Radiation Oncologist and Medical Physicist approval. The plan then enters the treatment preparation process and is eventually transferred to the treatment machine's Work List Manager (WLM) and Treatment Control Station (TCS) just before treatment. From the TCS, the machine format plan is transferred to the QA computer and the data compared to the DICOM plan for consistency and deliverability.

RESULTS: The product allows verification that the same plan that was reviewed by the Radiation Oncologist is the one that is about to be treated and verification of the integrity of the translation of the treatment field into machine code before treatment. Following these two verifications the patient is then treated.

CONCLUSION: Real time adaptive treatment planning requires new approaches to PSQA. The method presented here ensures fidelity of the real time plan at the time of treatment, eliminating the need for separate QA plan delivery and enabling real time treatment.

BACKGROUND: To analyze critical structure dose distributions using I-125 brachytherapy plaques and proton plans generated with a dedicated eye beamline for ocular melanoma treatment.

METHODS: Nine ocular melanoma tumor cases were treated at our institution with I-125 brachytherapy plans (prescribed to 85Gy at tumor apex delivered over 7 days) during proton cyclotron maintenance. Clinically comparable proton plans were generated for the same tumors on the 67.5 MeV eye beamline using EYEPLAN (prescribed to 56GyE in 4 daily fractions). Maximum absolute dose (Dmax) and maximum dose as a percentage of prescription (Dmax/%Rx) were extracted for optic disc (OD), macula, and lens, with the latter metric accounting for differences in prescription values between regimens. Due to the small sample size, distributions were compared using a nonparametric Wilcoxon matched pairs test with statistical significance at p-value<0.05.

RESULTS: Tumors characteristics were as follows [range (median)]: (a) maximum clinical basal diameter [6.7–15.8mm (9.7mm)]; (b) tumor height [1.1–10.75mm (3.4mm)]; and (c) OD-tumor distance [1.2–14mm (4.6mm)]. Dmax to OD was significantly different for protons versus plaques (p=0.01). Median (range) for Dmax OD was 0 GyE(0–52.1GyE) for protons and 40Gy(10–120Gy) for plaques, with 7 proton plans sparing the disc. Dmax/%Rx OD was also significantly different, 0%(0–93) and 47.1%(11.8–141.2) for protons and plaques, respectively (p=0.01). Dmax and Dmax/%Rx to macula was significantly different between protons and plaques, (p=0.01 and p=0.03, respectively) with the latter metric at 56%(0–94) versus 64.7%(11.8–225.9), respectively. Dmax to lens was significantly different at 2.8 GyE(0–56) for protons versus 16Gy(9–90) for plaques, respectively (p=0.02); Dmax/%Rx to lens did not differ at 5%(0–100) versus 18.8%(10.6–105.9), (p=0.37).

CONCLUSION: Dedicated eye proton beam plans demonstrated significantly different dose distributions compared with I-125 plaque plans with increased critical structure sparing and lower median doses for the optic disc and macula for both Dmax and Dmax/%Rx, and Dmax to lens.

BACKGROUND: The accuracy of dual-energy CT (DECT)-derived parametric maps is directly affected by the level of photon noise and image artifacts. Such inconsistency degrades the accuracy of the physics-based mapping technique and affects subsequent processing for clinical applications. In this study, we propose a deep-learning-based method to accurately generate a relative stopping power map (RSPM) as an alternative to physics-based dual-energy approaches.

METHODS AND MATERIALS: We manually segmented head-and-neck DECT images into brain, bone, fat, soft-tissue, lung and air, and then assigned different RSP values into the corresponding tissue types to generate a reference RSPM, which is the training target of our deep-learning model. We proposed to integrate a residual block concept into a cycle-consistent generative adversarial network framework to learn the nonlinear mapping between DECT and reference RSPM. This learning-based RSPM generation method was tested with 18 head-and-neck cancer patients. Mean absolute error (MAE) and mean error (ME) were used to quantify the differences between the generated and reference RSPM.

RESULTS: The average MAE between generated and reference RSPM was 0.031±0.004 and the average ME was 0.015±0.005 for all patients. Comparing to the physics-based method, the proposed method could significantly improve RSPM accuracy and had comparable computational efficiency after training.

CONCLUSIONS: We have developed a novel learning-based method to effectively capture the relationship between DECT data of tissue substitutes and reference RSPM, subsequently used it to generate accurate RSPM, and demonstrated its reliability. The proposed deep-learning-based approach has the potential advantages of producing unbiased and robust RSPM for proton dose calculation.

BACKGROUND: Compared to helical CTs, cone beam CTs (CBCT) have less accurate Hounsfield Units and degrade image quality, limiting their potential use for proton dose calculation. In this study, we developed a learning-based approach to accurately estimate relative stopping power (RSP) from to daily CBCTs, to enable future CBCT-guided online proton dose evaluation and adaptive proton planning.

METHODS AND MATERIALS: We first built a set of multiple paired training images including dual-energy CT (DECT) acquired for treatment planning and CBCT captured during the first treatment fraction. Then a deformable CBCT-DECT registration was performed to reduce anatomical differences between the images. The RSP mapping was generated using physics-based dual-energy approach to serve as training targets (ground truth). We used a cycle-consistent generative adversarial network framework with integrated residual block minimization to learn the nonlinear mapping between CBCT and DECT-based RSP map. This CBCT-based RSP generation algorithm was tested with 22 head-and-neck cancer patients with a leave-one-out cross-validation method. Mean absolute error (MAE), mean error (ME) and normalized cross-correlation (NCC) were used to quantify the differences between DECT-based and estimated RSP maps.

RESULTS: The average MAE and ME were 0.056±0.012 and −0.005±0.031 between DECT-based and CBCT-based RSP maps, and the mean NCC was 0.965±0.009 for all patients.

CONCLUSION: We have developed a novel learning-based method to generate accurate RSP mapping from daily CBCT imaging and demonstrated its reliability. The absolute value agreement and image similarity between DECT-based and CBCT-based RSP maps warrant further study and development of a CBCT-guided adaptive workflow for proton radiotherapy.

MedAustron is a dual particle therapy facility that started clinical operation with protons in December 2016 and is on schedule for the first patient to be treated with Carbon Ion Radiotherapy (CIRT) in July 2019.

Dose constraints for organs at risk (OARs) in carbon ion radiotherapy have been established in the clinical routine of already treating facilities but are, up to now, not completely harmonized.

In CIRT, as compared to photons and protons RT, it is less straightforward to derive dose constraints for OARs from published data especially because of the different RBE models employed.

Dose constraints based on the analysis of clinical outcome in patients treated with CIRT in Japan are available for: visual pathways, brainstem, brain, skin, rectum, duodenum and maxillary bone. These data are based on the Kanai semi-empirical / modified microdosimetric kinetic model (MKM).

Dose constraints based on German clinical data from patients treated with the local effect model (LEM-I) are available for the temporal lobes. Moreover unpublished constraints routinely used in clinical practice in Germany at the Heidelberg Ion Therapy Center (HIT), In Japan at National Institute of Radiological Sciences (NIRS) and at Gunma University (GHMC) and in Italy at National Center for Hadrontherapy (CNAO) have been generously shared by these Institutions.

The translation of mMKM constraints into LEM-I values is being extensively studied in CNAO. Ongoing activities encompass the analysis of toxicity and pattern of relapse in patients treated with Japanese schedule but using LEM-I and recalculation of LEM optimized plans with mMKM.

All these data were reviewed and were used to estimate dose constraints to be used in MedAustron with CIRT employing both a fractionation similar to HIT (3 Gy RBE per fraction at 5 fractions per week to a total of 20-22 fractions) and a fractionation similar to Japanese centers after conversion for different RBE models as performed in CNAO (4.1–4.8 Gy RBE per fraction at 4 fractions per week to a total of 16 fractions).

BACKGROUND: Data on the use of proton therapy for treatment of pediatric high grade glioma is limited. The purpose of this study is to report 4 year disease control.

METHODS AND MATERIALS: Patients aged ≤21 years with nonmetastatic intracranial high grade glioma treated with proton therapy were enrolled in a prospective outcome study. The Kaplan-Meier method was used to calculate survival and control rates.

RESULTS: From 2008 to 2019, 29 consecutive patients with a median age of 11.3 years (range, 2–20.5 years) received a median dose of 59.4GyRBE (range, 54–59.4GyRBE) using passive scatter proton therapy, most commonly with a 1cm initial CTV margin and no CTV expansion for the reduction. Majority of patients had gross total resection (GTR) (79%), while 21% had biopsy/subtotal resection (STR). 83% received chemotherapy. Median tumor size was 3.6cm (range, 1.5–7.6cm). The most common histologies included anaplastic astrocytoma (n=8) and glioblastoma multiforme (n=9). 52% of patients had WHO grade 3 tumors, 34% WHO grade 4, and 14% high grade not specified. With a median follow-up of 2.3 years for all patients and 3.7 years for living patients (range, 0.3–10.9), 4 year overall survival was 62% (95% CI, 41–79%) and 4 year progression-free survival was 52% (95% CI, 33–71%). 4 year local control was 53% (95% CI, 33–73%). 2/6 patients with STR/biopsy and 14/23 with GTR remained free of disease. Median time to local recurrence was 1.1 years (range, 0.05–6.2years). Only one patient developed distant disease without local progression. Two patients developed symptomatic local progression during radiotherapy.

CONCLUSION: Proton therapy for intracranial high grade glioma allows for conformal radiation delivery without marginal failures. Local control remains a challenge. Improved understanding of tumor biology and molecular composition may assist in identifying children with better prognoses who may benefit from advanced radiotherapy techniques that maximize normal tissue sparing.

PURPOSE: Acute skin reactions in patients with head and neck cancer (HNC) receiving radiotherapy are commonly observed. The grade of radiation dermatitis clinically varies according to dose. Concerns for greater skin reaction with proton therapy in head and neck patients have been raised. The purpose of this study is to quantify and verify skin doses relative to the underlying target volume (TV) prescription for patients with HNC receiving intensity modulated proton therapy (IMPT) to the bilateral neck.

METHODS AND MATERIALS: Skin doses were measured at specified locations using TLDs. IMPT plans used a SIB approach (dose range: 5600-7000 CcGE), had been optimized for TV coverage without a specific skin dose constraint, and used three fields (RAO, LAO, and PA). TLD powder packets were placed by a single radiation oncologist at four neck locations: R/L upper (level II) and R/L lower (level IV). TLDs were read following established dosimetry protocol.

RESULTS: The skin doses in the treatment plans were found to be linearly dependent on the distance of the point of interest to the edge of the TV (d). It was found to be 100% or more of the TV dose for d < 2 mm, reducing to about 90% at d=0.5 cm, and to about 70% at d=1.3 cm. TLD doses and the estimated doses from treatment plans agreed within +/−10%, with mean of deviation being close to 1%.

CONCLUSIONS: The skin doses in treatment plans compare reasonably well with TLD measurements on the skin surface. Additionally, skin dose sparing relative to the underlying TV prescription was observed, but varied according to its distance from the TV and the shape of the TV. Planning strategies to further reduce IMPT skin dose without compromising TV coverage are being explored.

BACKGROUND: Uncertainty in the value of relative biological effectiveness (RBE) of proton beam, especially in the distal dose fall off region, is an important consideration in designing safe treatment plans for proton therapy for many brain cancer patients where organs at risk (OARs) are located in the close proximity of target volumes. The purpose of this study is to explore novel strategies that can be used to mitigate the effect of RBE uncertainty in the proton therapy treatment plans for targets in the brain.

METHODS AND MATERIALS: Some of the treatment planning strategies applied to reduce the effect of RBE uncertainty are the use of: (1) suitable beam angles to minimize the dose to OARs from the distal fall off region of the field dose, (2) beam specific planning target volumes (BSPTVs) to force the beam stop further away from the OARs, (3) reduced biological effective doses (BEDs) to OARs by considering approximate higher RBE values in the longitudinal penumbral (LP) region of proton beam, and (4) multiple plans with different beam angles to spread the dose from LP region to different locations.

RESULTS: It was found that the use of the above strategies in designing treatment plans helped to reduce the BED of OARs so as to meet their required dose volume constraints. In many cases, use of multiple plans with different beam angles led to reduced doses to the OARs compared to one plan with limited beam angles while keeping the treatment delivery time same.

CONCLUSIONS: A combination of beam angle selection, use of BSPTVs, use of multiple plans and use of reduced BED dose constraints on OARs located in the longitudinal penumbra region of the proton beam are found to mitigate the RBE uncertainty in proton therapy plans for targets in the brain.

BACKGROUND: Layer and volumetric repainting can mitigate interplay effects, however they become ineffective for respiratory motion beyond 10 mm. In this retrospective study, heterogeneity effects of HFPV for motion greater than 10 mm is investigated.

METHODS AND MATERIALS: Five volunteers' free- and HFPV- respiratory chest wall motion curves were imported into a motion platform holding GAFChromic film which cycled accordingly. Their peak- to-peak free breathing (FB) amplitudes were >10 mm with mean frequency of 6.397 Hz (HFPV) and 0.2318 Hz (FB). Two matched fields were used to deliver a 3GyRBE 12×12cm square pattern. To evaluate uncertainties of hot and cold spot distributions, the plan was optimized as one Bragg peak. One motion curve was used to deliver the plan 5 times under free- and HFPV- motion. The plan was re-optimized to deliver 3GyRBE across a 7.5 cm SOBP. Films were placed at 6, 9, and 12 cm depths for each motion curve. Static films were irradiated for baseline. No repainting was performed.

RESULTS: Compared to free-breathing curves, hot and cold spots reduced from >30 % to <10 % using HFPV. Average Gamma pass rates at 3%3mm for HFPV- and free- breathing were 99.60 % (SD: 0.5) and 76.62 % (SD: 0.65), respectively. Although heterogeneity effects along the SOBP were greater for free-breathing motions, films placed at depths of 12 cm (Gamma: >50 %, SD: >9.0) were statistically different relative to those at 6cm (Gamma: >70 %,SD: >6 %) and 9cm (Gamma: >70 %, SD: >8 %) indicating heterogeneity effects for motion greater than 10 mm can vary along the SOBP while no significant difference was noticed for HFPV.

CONCLUSIONS: HFPV is a novel technique that significantly reduces heterogeneities from motion without repainting. HFPV is an effective technique that can be used to mitigate interplay effects that exist along the SOBP for motions larger than 10 mm.

BACKGROUND: Pediatric patients with rhabdomyosarcoma (RMS) of the bladder rely on definitive radiotherapy to achieve local control with bladder preservation. Proton therapy has been shown to confer dosimetric advantages over conventional photon radiotherapy. Here we describe the simulation, planning, and treatment techniques used to manage pediatric bladder RMS patients with proton therapy.

METHODS AND MATERIALS: With IRB approval, 5 pediatric patients <18y with bladder RMS, treated with proton therapy, were identified. Clinical and radiation treatment planning data were retrospectively abstracted from the electronic medical record.

RESULTS: Median age at simulation was 2.4y (range 1.3–4.9y). Four of 5 presented with de novo disease, and 1/5 presented with a bladder recurrence of a vaginal RMS previously managed without radiotherapy. All had embryonal or fusion-negative disease. Among the 4/5 with de novo presentation, all had Group 3, 2/4 had Stage 2, and 2/4 had Stage 3 disease. In 4/5 patients, simulation and treatment setup was performed with the bladder filled to 50–70 mL via an 8 French urinary catheter, which was then clamped. Four of 5 patients were planned to a total dose of 50.4 CGE; 1/5 was treated to 41.4 CGE. The CTV was asymmetrically expanded to account for proton distal range uncertainty. The bladder, femoral heads, large bowel, and rectum were contoured. Beam arrangements include left and right posterior obliques in 4/5, and 2 left posterior obliques in 1/5. Among the 4/5 patients treated to 50.4 CGE, mean dose to the bladder was 36.6 CGE (±13.5), femoral heads 1.3 CGE (±1.0), and rectum 44.4 CGE (±10.3); average maximum dose to the large bowel was 4.1 CGE (±3.1).

CONCLUSIONS: With attention to simulation, planning, and daily setup, proton therapy can offer pediatric RMS patients accurate, reproducible target coverage and excellent organ-at-risk sparing.

BACKGROUND: Proton therapy has undergone dramatic technical evolution with regard to treatment delivery in the past decade. These advancements, including the evolution from double scattered proton therapy to pencil beam scanning, as well as improved imaging, have expanded the ability to treat more disease sites. This study evaluates the impact of technology changes on both proton therapy and conventional x-ray radiation patient treatment volumes at a center with both modalities available under one roof.

METHODS AND MATERIALS: Between 1/2010 and 2/2018, 21,482 patients were treated with radiation at the Perelman Center for Advanced Medicine protons and/or conventional radiation. Proton therapy was delivered to 5416 patients. Data for each patient were recorded through ARIA and interfaced with Tableau. Volumes of new patient starts (NPS) were tracked by modality, provider, and disease site across multiple fiscal years. Analysis of changes in NPS was performed based on the trends and addition of new technologies.

RESULTS: There has been a 64.2% increase in NPS volume since the opening of the Roberts Proton Center at the main academic site in 2010. As more treatment rooms were opened and the technology was updated, the number of proton NPS gradually increased, until reaching a plateau of about 820 NPS per year. Conventional volumes have increased 20.2% during the same timeframe at this location. Technology advancements have expanded disease site utilization of proton therapy diversifying and expanding treatment from 7 original disease sites in 2010 to 14 in 2018. For example, head and neck cancer NPS volumes increased from 2% to 12.7% with the addition of PBS on the gantry.

CONCLUSIONS: Our analysis shows that the addition of proton therapy to a conventional radiation department increases the overall NPS volumes, having a positive impact on conventional treatment volumes. This volume increase appears to be related to the technology advancements in PBS and imaging instruments.

BACKGROUND: To determine which factors influence insurance approval for patients seen in consultation following breast cancer surgery for whom adjuvant proton therapy (PT) was recommended.

METHODS: 131 insured patients were seen in consultation April 2014–November 2018 and recommended adjuvant PT as part of definitive treatment. 108 patients (82%) had Tis-T2 cancers; 23 (18%) had T3–T4 malignancies. Laterality included right, 26 patients (20%); left, 105 (80%). Four patients with bilateral cancers were lateralized and staged according to the more advanced side. Forty-three patients (33%) had N0 cancers; the remainder had N1–N3. Adjuvant chemotherapy was administered to 97 patients (74%); 72 (55%) received adjuvant hormonal therapy. Insurance status included commercial, 76 patients (58%); Medicare, 41 (31%); and Medicaid, 14 (11%). Ninety-six (73%) had policies that “covered” PT. Insurance “coverage” for PT did not assure approval for PT treatment nor did lack of “coverage” mean PT would not be approved. Factors for multivariate analysis of predictors for insurance approval included T stage (‘Tis-T2 vs T3–T4); N stage (N0 vs N1–N3); laterality (left or bilateral vs right); insurance type (commercial vs Medicare/Medicaid) combined with potential insurance coverage (covered vs not covered); and time period (2014–2016 vs 2017–2018).

RESULTS: Medical review was required for 73 patients (56%); peer-to-peer review for 20 (15%); comparative dosimetry for 34 (26%). One patient (1%) appealed the insurance denial to a federal administrative law judge. Insurance approval stratified by insurance type and coverage included commercial-covered, 52/52 patients (100%); Medicare/Medicaid-covered, 41/44 patients (93%); commercial-not covered, 16/22 patients (73%); and Medicare/Medicaid-not covered, 7/13 patients (54%). Multivariate analysis revealed the following: T stage, p=0.4268; N stage, p=0.4046; laterality, p=0.1070; insurance type combined with potential coverage, p<0.0001; and time period p=0.1647.

CONCLUSION: Laterality and stage were not associated with approval. The only parameter significantly associated with approval was insurance type combined with potential coverage.

BACKGROUND: Robust perturbations are a key component in pencil beam scanning proton therapy plan evaluation. A physicist can evaluate the isocenter shifts, rotations, and range perturbations for a treatment plan to assess the sensitivity of the proton plan to various uncertainties. The production and evaluation of these perturbations can be tedious and time consuming. We have developed a script to automate the calculation of at least 18 unique perturbations and output the DVH data for targets and OARs to an html file for quick and efficient physics evaluation.

METHODS AND MATERIALS: We developed a Python script, run in RayStation, that allows the user to choose setup shifts, range uncertainty, setup rotations, and independent beam isocenter shift perturbations. The user also chooses the targets and OARs to be exported. The script then calculates each of the perturbations in RayStation and exports the data to a JSON file that can be read in html. The output displays each target and OAR DVH for every perturbation on a single graph. The user can turn target and OAR DVH visualization on and off, as well as turn perturbations on and off. The data is also summarized in a table, visualizing the max dose and max dose deviation from nominal for each OAR. For each target, the max dose, max dose deviation from nominal, D95%, and D95% deviation from nominal are shown.

RESULTS: This script has standardized robust perturbation calculation and evaluation across all of dosimetry and physics. Dosimetry can visualize robustness before a plan is complete, allowing more efficient plan improvements and reducing plan failure by physics. Physics evaluation time has been significantly reduced.

CONCLUSIONS: This robust evaluation script has reduced plan failures following optimization, improved perturbation standardization, and reduced evaluation time for dosimetry and physics.

BACKGROUND: Uncertainties associated with CT-derived proton stopping power ratios (SPR) are a limiting factor in exploiting the full benefits of proton therapy. We investigate the feasibility of a model that predicts SPR using MRI-measured material hydrogen densities.

METHODS AND MATERIALS: A model (SPR-H) that related the medium's hydrogen density with its SPR was constructed by considering twenty-two materials taken from the National Institute of Standards and Technology (NIST) database. Subsequently, the model was used to predict the proton range and water equivalent thickness (WET) for nine tissue-surrogate materials of CIRS phantom, and the predicted values were compared with measurements using a multilayer ionization chamber (MLIC), as well as the treatment planning system (TPS) calculated WET. Additionally, a phantom setup was designed and irradiated and for each plug, ion-chamber measured dose was compared to the TPS dose calculations based on SPR-H model. For further validation, proton-density and T2-weighted MRI scans of twelve salt-water solutions with different salt concentrations (hydrogen densities) were used by the SPR-H model, and the model- predicted SPRs were compared with their corresponding MLIC measurements.

RESULTS: MRI pixel values of both scans correlated well with the measured SPRs. For all salt-water solutions and tissues-surrogates (except lung), model predicted SPR and WET were within 3% and 2% of the measurements and TPS predicted values. Additionally, the SPR-H predicted and measured doses were within 1.5% agreement. Larger deviations of 9% for SPR, and 2.6% for dose were observed for lung-tissue.

CONCLUSIONS: SPR predicted by SPR-H model can facilitate dose calculation while reducing range uncertainty in proton therapy.

BACKGROUND: To evaluate the clinical usability of a flat-panel based compact PBS daily QA device for constancy measurements of beam spot characteristics, beam energies, flatness of Spread-out-Brag-peak (SOBP), output, X-ray/proton coincidence, and area uniformity.

METHOD AND MATERIALS: The phantom device is composed of a 20×20cm2 flat-panel imager mounted on a portable frame with removable/re-configurable modules (high density plastic blocks dedicated for energy checks of 100, 150, 200 MeV protons and SOBP flatness checks, RW3 block for PPC05 chamber based output checks). X- ray/proton spot coincidence, spot location accuracy, and area uniformity checks can be performed on open area of the imager. For x-ray/proton spot coincidence checks, 3 types of radio-opaque BBs were evaluated. For spot location checks, maps of spots with 1mm, 2mm and 3mm shifts were acquired and compared to the original maps. For energy checks, maps were acquired and analyzed for modified plans with 0.1 MeV increase/decrease from the 3 energies for a continuous energy degrader system and for 1, 2 and 3 energy steps increases/decreases for a stepped energy degrader system. Detector quenching effect was evaluated with different proton energies. For SOBP flatness evaluations, maps were acquired using a full modulation SOBP delivered through different sections of the wedge block.

RESULTS: The daily QA device detected millimeter changes of spot location and detected 0.1 MeV energy changes with its energy blocks; up to 8% quenching effect was observed from 100 to 227 MeV and can be corrected to obtain water equivalent results. Full-modulation SOBP delivered through thicker half of the wedge block mitigated the impact of quenching effect and rendered flat representations of the SOBP. Area uniformity is within 2%.

CONCLUSIONS: The flat-panel based compact daily QA device is capable of efficient daily checks of x-ray/proton coincidence, beam spot location and energy, area uniformity, and flatness of SOBP.

PURPOSE: To evaluate the dosimetric and radiobiological impact of PB algorithm versus MC algorithm in intensity-modulated proton therapy (IMPT) plans for breast cancer treatment.

METHODS AND MATERIALS: Twenty (20) breast cancer patients (stage T1–T2, post-mastectomy or post-lumpectomy) who received adjuvant proton IMPT radiotherapy to the breast/chest wall and regional lymphatics were included in this study. For each patient, 2 IMPT plans were generated: a PB-optimized plan and a MC-optimized plan. The radiobiological and dosimetric impact of the dose algorithms was assessed. The Poisson Linear-Quadratic model was used to estimate the tumor control probability (TCP). The influence of the model parameter uncertainties on the TCP was tested against different sets of published model parameters. In addition, we also studied the influence of α/β ratios.

RESULTS: The PB-optimized plans significantly under-dosed the target as compared to the MC-optimized plans. The median (range) differences in CTV D95% and CTV Dmean were 3.8% (2.4% - 6.2%) and 2.4% (1.0% - 3.8%) of the prescription dose. The median (range) difference in CTV V95% was 20.8% (0.9% - 41.8%). The TCP was lower in the PB-optimized plans than the MC-optimized plans. The α/β ratios has minimal influence on the calculated TPS. The median (range) of the TCP differences (ΔTCP) were 4% (2% - 6%), 3% (2% - 5%), and 2% (1% - 3%), respectively, when calculated using 3 different model parameter sets. The ΔTCP correlated with the CTV dose difference, and moderately correlated with the CTV volume.

CONCLUSION: Due to the inaccurate dose modeling, PB-optimized plans under-dose the target and therefore yield a lower TCP compared to MC-optimized plans in breast IMPT. The magnitude of the resulting difference in TCP reached 6% in our study.

INTRODUCTION: Paranasal sinus cancers are challenging to irradiate due to proximity to eyes, lenses, optic nerves, chiasm and brainstem. These tumors often have adverse pathologic features, necessitating high radiation doses for cure, which may exceed tolerance of the optic pathways. This is the first known study of paranasal sinus and nasal cavity cancers to evaluate potential dosimetric improvements by using a novel proton therapy modality: Spot-Scanning Proton Arc (SPArc).

METHODS AND MATERIALS: Ten patients with sino-nasal cancer undergoing high dose (60–66 GyE) Intensity Modulated Proton Therapy (IMPT) based on the Single-Field Optimization (SFO) were re-planned with SPArc technique, using Monte Carlo dose calculation. Clinical IMPT plans using multiple static fields, including vertex beams, were compared to SPArc plans using an axial and/or vertex arc with 2.5 degree control point sampling frequency.

RESULTS: With similar target coverage, maximum point doses (in GyE, to 0.03 cm3) for organs at risk were as follows for SFO IMPT versus SPArc plans, respectively: Ipsilateral Lens 12.14 vs 3.71, Contralateral Lens 7.63 vs 2.25, Ipsilateral Eye 46.15 vs 36.55, Contralateral Eye 35.59 vs 27.59, Ipsilateral Optic Nerve 53.69 vs 41.52, Contralateral Optic Nerve 49.44 vs 36.85, Optic Chiasm 39.49 vs 31.32, Brainstem 46.02 vs 31.01 GyE; all with p<0.05.

CONCLUSIONS: SPArc has the potential to significantly reduce maximal dose levels to the eyes by approximately 8 GyE, and to the optic nerves by 12 GyE beyond what was clinically delivered with IMPT plans. SPArc is capable of providing new and clinically meaningful optic pathway sparing, potentially reducing the risk of cataracts and vision loss.

PURPOSE: This study is to quantitatively evaluate the effectiveness of motion interplay mitigation via spot-scanning proton arc (SPArc) therapy for lung stereotactic body radiotherapy (SBRT).

METHODS AND MATERIALS: A set of digital lung tumor (diameter:4cm) phantoms 4DCT with different breathing induced motion in superior inferior (SI) direction (with amplitudes: 5, 10, 15 and 20mm) were created to mimic mobile lung SBRT targets. Two-field Intensity Modulated Proton Therapy (IMPT) plans were generated with single field optimization (SFO) technique and SPArc plans were generated using a partial arc from 180 to 30 degree with sampling frequency of 2.5 degree. Both plans used the same robust optimization parameter with ±3.5% range and 5mm setup uncertainties. 6000cGy relative biological effectiveness [RBE] was prescribed to internal target volume (ITV) in 5 fractions. To assess the breathing induced interplay effect, the 4D dynamic dose was calculated by synchronizing the breathing pattern with the simulated proton machine delivery sequence. Volumetric (IMPTvol_rep) and iso-layered (IMPTiso_rep) repainting technique using IMPT were compared with SPArc treatment respectively.

RESULTS: Target coverage degraded as the tumor motion amplitude increased. SPArc significantly mitigated the interplay effects in comparison with the IMPT without volumetric repainting through all the different motion amplitudes. More specially, the average target D99 degradation were 2.51% (IMPT) vs 0.0% (SPArc) (p=0.001), 4.01% (IMPT) vs 0.10% (SPArc) (p<0.001), 6.61% (IMPT) vs1.29% (SPArc)(p<0.001), 8.40% (IMPT) vs 1.70% (SPArc) (p<0.001) respectively. Target coverage can be compensated by increasing the total number of repainting in IMPTvol_rep and reducing the maximum MU per spot in IMPTiso_rep. The study found that the effectiveness of such motion mitigation using SPArc was about 5 to 7 times of IMPTvol_rep, as well as from 1.0 to 0.4 MU per spot at 2cm motion amplitude. With increased number of repainting, the deliver time increased to 698s in IMPTvol_rep compared to 490s in SPArc.

CONCLUSIONS: SPArc is capable to effectively mitigate the interplay effect in lung SBRT depending motion amplitude.

BACKGROUND: MedAustron is Austria's synchrotron-based dual particle therapy facility under operation with protons since December 2016. Until June 2019, 400 patients were successfully treated in 2 treatment rooms using horizontal and vertical fixed-beam lines. By early 2019 carbon ion acceptance and medical commissioning started. We report on first commissioning results and specificities of MedAustron's carbon ion therapy system.

METHODS AND MATERIALS: Dosimetry equipment was commissioned for carbon ions and used to measure the following beam properties: 242 energies from 120–402.8MeV/n (ranges in water from 2.9cm–27cm in 1mm steps using 2 crossed 1D Ripple Filters), spot sizes (in FWHM at isocenter in air) from 6mm to 10mm. The patient positioning system was designed for non-isocentric, air-gap reduced setups. This allows decreasing treatment penumbra and reducing uncertainty for pencil beam algorithm-based dose calculation using a range shifter (RaShi) mounted in the nozzle. Hence, the beam delivery system as well as the TPS using the LEM-I RBE-model were commissioned for different air gaps from 7cm to 65cm.

RESULTS: Measured ranges in water at isocenter agreed within 0.3mm with the specified. Circular shaped spots (roundness tolerance; 10%/1mm) could be achieved for the whole air gap range. TPS commissioning showed very good results for setups close to the nozzle with and without RaShi. Only for isocentric treatments the carbon pencil beam algorithm cannot model RaShi beams with sufficient accuracy and hence only non-isocentric setups (reduced air gap as for protons) will be used.

CONCLUSION: The commissioning results for the fourth European carbon facility are very promising and the process is on time. TPS commissioning results in non-isocentric patient setup are in very good agreement with measurements. It is the first time that the carbon functionality within RayStation 8B will be clinically used and hence final integrative checks as well as the specifically developed dosimetric e2e audit procedures are performed. Patient start is expected in the first week of July.

PURPOSE: Proton beam therapy treatment planning can be impacted by linear energy transfer (LET). Higher LET is correlated with higher radiobiological effectiveness. This work seeks to investigate the feasibility of enhancing the average LET in the gross tumor volume (GTV) for pancreas cancer treatment with intensity modulated proton therapy.

METHOD AND MATERIALS: The LET enhanced treatment planning optimization was performed with a gradient based and iterative optimization algorithm. Two aspects contributed to LET enhancement. 1) Extra beams from different directions. Additional beams permitted putting Bragg peaks in GTV while maintaining prescription dose. 2) Proton beam spot was iteratively weighted by LET ratio between target and organs at risk during optimization. The resulting LET enhanced optimization plan was compared with the conventional pancreas proton plan that was used to treat the patient. The conventional plans were optimized with two posterior oblique fields and no LET weighting in optimization. All dose and LET was computed by an in-house Monte Carlo.

RESULTS: Average LET could be enhanced from ~2keV/um to 4–5keV/um. The magnitude of LET enhancement depended on GTV size, GTV location with clinical target volume (CTV), robustness of the plans, etc. When additional anterior beams were utilized, LET enhanced plans had additional dose delivered to bowels at low dose level. The highest LET enhancement was achieved in plans with worst robustness to range uncertainties.

CONCLUSIONS: LET enhancement in the GTV was feasible for pancreas cancer proton beam therapy. Various factors including plan robustness and low dose spillage should be taken into account during planning.

BACKGROUND: In the absence of motion management, respiratory tumor motion and the presence of cycle-to-cycle variations greatly degrades the accuracy of radiation targeting. By measuring the volumetric tidal flow, spirometry has been shown to be an accurate surrogate for internal displacement. However, spirometers are prone to drift. We investigate the performance in estimating volumetric tidal flow when integrating higher order information associated with monitoring the entire thoraco-abdominal surface rather than the commonly used technique of monitoring a single patch/point.

METHOD AND MATERIALS: Breathing patterns of five healthy volunteers was recorded simultaneously using two common, non-invasive breathing methods: volumetric tidal flow using spirometry (SDX, Dyn'R, France), and abdominal height displacement with Real Time Position Management (RPM, Varian, USA). Simultaneous to the two measurements, a prototype, research version, optical surface imaging system (AlignRT, Vision RT, UK), was used to capture a dense point- cloud of the thoraco-abdominal surface with a rate of 15fps and reconstructed as a watertight surface on a rectangular grid to perform a principal component (PC) analysis. The RPM signal, and the first three components of the surface were normalized. The first ten seconds of the measurement was used to train a principal least square model to estimate volumetric tidal flow for the remaining 100 seconds.

RESULTS: Both surface surrogates (RPM and VisionRT) showed a high degree of correlation with tidal flow. In comparison to the RPM, a three PC surface model leads to a reduction in estimated tidal flow RMSE by as much as one order of magnitude. One volunteer exhibited a one dimensional breathing pattern with the first surface PC correlated with tidal flow correlated (RMSE=0.001).

CONCLUSIONS: Our study suggest that monitoring the entire surface rather than a single point can lead to improvements when estimating tidal flow, and hence represents a more accurate breathing metric.

BACKGROUND: The accuracy of stopping power ratio (SPR), particularly for low density materials such as lung tissue, is a limiting factor in proton therapy plan robustness. We investigate the potential improvements associated with the use of dual-energy CT (DECT) for estimating SPR of lung tissue samples.

METHOD AND MATERIALS: Single energy CT (SECT) and DECT scans of six sheep and one cow lung tissue samples were acquired on a Siemens SOMATOM Definition Edge CT. SPR images were created for each lung samples from the DECT generated relative electron densities (ρe) and effective atomic numbers (Zeff). To calculate water equivalent thickness (WET), the generated SPR and acquired SECT images were imported into Eclipse (v13.7, Varian Medical Systems, Palo Alto, CA) treatment planning system (TPS). The SPR-to-SPR (straight line with a slope 1) and clinical HU-to-SPR calibration curves were applied to the SPR and SECT image sets, respectively to calculate water equivalent thickness (WET) and SPR of each lung tissue sample. For each sample, the calculated SPR values estimated from SECT and DECT scans were compared with the measurement performed using a multilayer ionization chamber (MLIC).

RESULTS: For all lung tissue samples, for SECT the TPS WET was less than the measured WET by 15% to 28% (average=21.0%). For DECT, the TPS calculated WET values were within ±8% (average=3.1%) of the measurement. Similarly, DECT derived SPR values agreed with the measurements to within ±8% (average=5.22%) for sheep and 0.54% for cow lung tissues, whereas SECT derived values (using HU-to-SPR calibration) deviated from measurement by as much as 38% (sheep: <38%, average=28.34% and cow =18.26%).

CONCLUSION: Our study suggests that using DECT can improve the accuracy of SPR and WET predictions for low density tissues such as lung.

PURPOSE: To assess the role of CT-QA scans for IMPT when treating head and neck malignancies and to determine risk factors associated with the need for adaptive replanning.

METHODS AND MATERIALS: A prospectively collected quality improvement study of patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of an adaptive re-plan by week. Risk factors associated with adaptive re-planning were determined using univariate and multivariate cox models. Logistic regression was used to determine odds ratios.

RESULTS: Of the 160 patients, 79 (49.4%) had verification CT-QA scans which prompted an adaptive re-plan. The cumulative probability of a re-plan by week 1 was 13.7% (95%CI: 8.82–18.9), week 2, 25.0% (95%CI: 18.0–31.4), week 3, 33.1% (95%CI: 25.4–40.0), week 4, 45.6% (95% CI: 37.3–52.8), and week 5/6, 49.4% (95%CI: 41.0–56.6). Predictors for adaptive re-planning were sinonasal disease site (UVA:HR 1.82, p=0.0443; MVA:HR 3.64, p=0.0303), advanced stage disease (UVA:HR 4.68, p=0.0016; MVA:HR 3.10, p<0.05), dose >60 GyE (RBE 1.1) (UVA:HR 1.99, p=0.0035; MVA:HR 2.20, p=0.0079), primary disease (UVA:HR 2.00 vs. recurrent, p=0.0133; MVA:HR 2.46, p=0.0138), concurrent chemotherapy (UVA:HR 2.05, p=0.0023; MVA not SS), definitive intent treatment (UVA:HR 1.70 vs. adjuvant, p=0.0179; MVA not SS), bilateral neck treatment (UVA:HR 2.07, p=0.0340; MVA not SS), and higher number of beams (5 beam UVA:HR 5.55 vs. 1 or 2 beams, p=0.0157; MVA not SS). Maximal weight change from baseline was associated with higher odds of a re-plan (≥3kg OR 1.97, p=0.0438; ≥5kg OR 2.13, p=0.0246).

CONCLUSIONS: An adaptive replan was required for nearly half of patients undergoing IMPT for head and neck malignancies because of unacceptable deviations in the dose distribution. Weekly CT-QA scanning for head and neck cancer patients treated with spot-scanning IMPT is essential.

BACKGROUND: Magnetic resonance imaging (MRI) has been increasingly utilized for target delineation, treatment-response evaluation and plan adaptation of prostate cancer radiotherapy. The purpose of this study is to evaluate the feasibility and accuracy of a deep-learning based synthetic CT(S-CT) generation method for MR-only proton treatment planning of prostate cancer.

METHODS AND MATERIALS: A 2-D U-net was trained from paired CT and T2-weighted MR images of 36 prostate patients to generate S-CT from MR. Ten additional patients, randomly selected from previous-treated patients in our institution, were included in this study. S-CTs were generated from MR T2 images and evaluated against original CTs. The discrepancy of CT number was analyzed in terms of MAE (Mean absolute error). Intensity modulated proton therapy (IMPT) plans with two opposed lateral beams were optimized on the original CT with a prescription dose of 79.2Gy(1.8Gy×44fx). The plans were then calculated on both original CT and S-CT with Monte Carlo algorithm and 1-mm resolution to get the final doses. The dose discrepancy was evaluated by the DVH parameters of target and critical organs, as well as the 3D-gamma passing rate.

RESULTS: The computational time for generating a new S-CT was 3.84–7.65 s. The MAE(mean±Std) between the original CT and sCTs was 30.23±5.53HU. The gamma passing rate (global 3D gamma, 10% threshold) is 93.17%, 99.56% and 99.90 for 1%/1mm, 2%/2mm, 3%/3mm criteria, respectively. The differences in target DVHs were 0.1±0.2% and 0.1±0.3% for D99, D95, respectively. For critical organs, Rectum D5, Bladder D40 and femoral head D2 have a difference of −0.3%±0.8%, 0.1±1.7%, and −0.1±0.2, between S-CT and original CT.

CONCLUSIONS: The proposed U-net can generate S-CTs that are in good agreement with original CTs for proton planning purpose in a few seconds. An efficient MRI-only planning and adaptation workflow is potentially feasible for proton therapy in prostate cancer.

BACKGROUND: Pencil beam proton therapy often has inferior lateral penumbra compared to photon-based therapy at clinically relevant depths. We test the hypothesis that by using layer-by-layer adaptive aperture (AA), it would be possible to achieve sharper penumbra compared to that achieved with conventional photon therapy at typical tumor target depths.

METHOD AND MATERIALS: The Mevion Hyperscan Pencil Beam Scanning system, consisting of an in-line range shifter and layer-by-layer mechanical aperture was used to measure lateral penumbra (distance between the 80%–20% dose levels) of a 10×10cm field at varying depths. Measurements were taken with and without a 10cm-thick bolus and with varying air gaps (AG), with and without AA. This was compared to penumbra from 6MV photons delivered using a Varian Trilogy system.

RESULTS: Most of our Hyperscan treatments require at least a 10cm AG, which can often be reduced to 3cm or less using a 10cm-deep bolus attached to the head. AA reduces measured penumbra by about 1/3 at shallow, clinically relevant depths. Use of 10cm bolus with 3cm AG leads to significant flattening of penumbra by 32% compared to 10cm AG with adaptive aperture, and a reduction of 54% compared to using 10cm AG without adaptive aperture. While 6MV photons have sharper penumbra below 11.5cm for protons without AA at 10cm AG, the sharper lateral penumbra for photons is reduced to depths below 7cm when 3cm AG with AA is used.

CONCLUSIONS: AA permits approximately 30% sharper penumbra at shallower depths clinically applicable for most superficial tumor targets. Use of layer-by-layer AA combined with bolus and smaller AG significantly decreases the depth at which protons start to have tighter lateral penumbra compared to 6MV photons.

BACKGROUND: Range uncertainty is a major limiting factor in precision targeting of charged particle therapy. Ongoing efforts investigating accurate prediction of energy deposition would benefit from knowledge of the actual dose deposited in tumor and normal structures. Current dosimetric techniques measure the total or average energy deposited, but do not capture individual particle energy which may have distinct biological properties depending on its location within the Bragg curve. To address this, we developed a sub-cubic millimeter single particle dosimeter measuring particle flux and individual particle linear energy transfer (LET).

METHOD AND MATERIALS: A 1mm×0.5mm×0.3mm dosimeter consisting of 2,048 sensing elements was designed and fabricated in a 65nm complementary metal oxide semiconductor process. Each sensing element contains a differential pair of 1μm2 photodiodes; a proton hit produces a transient voltage pulse of 9.5–309mV, proportional to particle LET. Pulse duration, monotonic function of the energy deposited (LET), was measured. The sensor was placed in 67.5MeV proton beam (Crocker Nuclear Laboratory, UC Davis). Current (particle flux) was varied from 0.1–3nA and water column thickness (WCT) was varied from 0–3cm. TOPAS was used to simulate sensor response.

RESULTS: LET of individual protons was measured. Increasing beam current from 0.1 to 3nA resulted in a measured particle flux of 1.08×104–2.6×105 protons/s/mm2. At 3nA, the mean LET increased with water column thickness; the Bragg peak was identified at 2.7cm, with a pulse duration 1.76 times that of the entry dose. Flux decreased slightly with increasing WCT and rapidly fell off after the Bragg peak. The tail consisted of a few high LET protons.

CONCLUSION: We have demonstrated single particle LET detection in a clinical proton beam. Direct implantation of these devices can yield real time single particle in vivo dosimetry, improving accuracy of treatment planning and removing range uncertainty even in the setting of tumor and OAR motion.

BACKGROUND: Range uncertainty is a major limiting factor in precision targeting of charged particle therapy. Ongoing efforts investigating accurate prediction of energy deposition would benefit from knowledge of the actual dose deposited in tumor and normal structures. Current dosimetric techniques measure the total or average energy deposited, but do not capture individual particle energy which may have distinct biological properties depending on its location within the Bragg curve. To address this, we developed a sub-cubic millimeter single particle dosimeter measuring particle flux and individual particle linear energy transfer (LET).

METHOD AND MATERIALS: A 1mm×0.5mm×0.3mm dosimeter consisting of 2,048 sensing elements was designed and fabricated in a 65nm complementary metal oxide semiconductor process. Each sensing element contains a differential pair of 1μm2 photodiodes; a proton hit produces a transient voltage pulse of 9.5–309mV, proportional to particle LET. Pulse duration, monotonic function of the energy deposited (LET), was measured. The sensor was placed in 67.5MeV proton beam (Crocker Nuclear Laboratory, UC Davis). Current (particle flux) was varied from 0.1–3nA and water column thickness (WCT) was varied from 0–3cm. TOPAS was used to simulate sensor response.

RESULTS: LET of individual protons was measured. Increasing beam current from 0.1 to 3nA resulted in a measured particle flux of 1.08×104–2.6×105 protons/s/mm2. At 3nA, the mean LET increased with water column thickness; the Bragg peak was identified at 2.7cm, with a pulse duration 1.76 times that of the entry dose. Flux decreased slightly with increasing WCT and rapidly fell off after the Bragg peak. The tail consisted of a few high LET protons.

CONCLUSION: We have demonstrated single particle LET detection in a clinical proton beam. Direct implantation of these devices can yield real time single particle in vivo dosimetry, improving accuracy of treatment planning and removing range uncertainty even in the setting of tumor and OAR motion.

BACKGROUND: Patients undergoing brain irradiation indicate unpleasant chemosensory changes during treatment. The ability to predict when unpleasant changes occur will lead to better patient compliance. This study evaluates the correlation between brain proton irradiation and the effects on the olfactory system.

METHOD AND MATERIALS: Fifteen patients were enrolled in a prospective study. All patients received proton PBS craniospinal irradiation with a posterior fossa boost. Patients depressed a buzzer when taste/odor was detected and again when taste/odor dissipated, for three consecutive days. Monitor units and layer were recorded for each buzz and correlated with dosimetry/treatment layer. A Post-treatment survey identified the negative chemosensory description/intensity. Assessment of the number of overlapping days the taste/odor change occurred and coloration between the layer-defined OS dose and Bragg peak location, in proximity to the OS occurred.

RESULTS: All 15 patients experienced changes in odor and 5 noted changes in taste. 9 patients buzzed after every layer indicating no smell detected during the pause between layer switching. On average, patients indicated the odor/taste was moderate/difficult to tolerate (sewer, burning, chlorine). Mean incidence dose to olfactory structures reported on days 0, 1, 2, and 3 were 0.4, 2.7, 4.9, and 16.5 cGyRBE respectively. This best fits a normal-tissue complication probability model yielding a TD50 of 4 cGyRBE. The number of days which layers overlapped the taste/odor period correlates with the OS proximal to the Bragg peak (p=0.036). For layers causing 100% odor change, the OS was proximal to the Bragg peak 95% for all 3 days. Nasal cavity dose was zero in all cases.

CONCLUSION: During brain irradiation, taste/odor changes correlate with the timing of layer-defined dose delivery to the OS and the location of the Bragg peak proximal to the OS. Radiation-induced chemosensory changes that contribute to the taste/odor changes, during irradiation, may be able to be predicted.

PURPOSE: Using a quantitative decision-support system to estimate the quality of life burden from normal tissue complications (NTCs) after definitive RT for oropharyngeal cancer (OPC), comparing photon and proton RT.

METHOD AND MATERIALS: The normal tissue complication probability (NTCP) for dysphagia, esophagitis, hypothyroidism, xerostomia and oral mucositis was estimated for 33 OPC patients, comparing delivered photon IMRT plans with intensity- modulated proton therapy (IMPT) plans generated using clinical protocols at a collaborating PT center. Plans had equivalent target coverage and robustness optimization was used for IMPT plans. Latencies and durations of NTCs were modeled while accounting for the disease-specific age-, sex-, and smoking status-adjusted conditional survival probability. The quality- adjusted life years (QALYs) lost attributable to each NTC were calculated by assigning quality-adjustment factors based on complication severity. Cost effectiveness was modeled based on the upfront cost of IMPT ($36,659) and IMRT ($20,257), and interventions related to NTCs, with 3%/year discounting of QALYs and long-term costs.

RESULTS: The average QALYs lost from all NTCs were 1.52y and 1.15y for IMRT and IMPT, respectively, with average 0.37y spared with IMPT (95% CI: 0.27y–2.53y). The QALYs spared with proton RT varied considerably between patients, from 0.06 to 0.84 QALYs. Younger patients with p16-positive tumors and ≤10 pack-years smoked had the greatest estimated benefit of average 0.56 QALYs. IMPT cost effectiveness varied greatly between patients with a wide variety of incremental cost effectiveness ratios (ICERs), which are a measure of cost per spared QALY.

CONCLUSION: Using this decision-support tool we identified patients for which IMPT is estimated to have the greatest benefit and would be most cost effective. This can help optimize resource allocation and patient selection for trials aimed at improving the quality of life for OPC patients.

BACKGROUND: Patients with CNS and skull base tumors treated with proton therapy undergo repeated neurocognitive testing as part of our Registry Study. 112 of 114(98%) eligible patients performed the tests. We report on feasibility, patient acceptance, and early results.

METHOD AND MATERIALS: A battery of standardized EORTC tests was employed. The Hopkins Verbal Learning Test (HLTV-R) tests immediate and delayed verbal memory. Trail Making Test Part A and B (TMT-A und B) assesses concentration, processing speed and cognitive flexibility. The Controlled Oral Word Association Test (COWA) evaluates verbal fluency and executive function. The Grooved Pegboard Test evaluates visual motor coordination. Tested time points were at baseline, at treatment completion, at 3, 6,12 months and once yearly thereafter. Testing time for every period were 30 minutes.

RESULTS: The first 4 time points (baseline, treatment end, at 3 and 6 months) were evaluated in 112, 94, 61 and 40 patients. Test completion rates were 99%, 96%, 98%, and 98 % at the time points. No significant differences were found in verbal memory (HVLT-R), cognitive flexibility, executive function (TMT-B) and motor coordination. Between baseline and at 6 months significant worsening was found in speed processing (TMT-A, p=.002), however, significant improvement in verbal fluency (COWA, p=.000).

CONCLUSION: First and early results on neurocognitive function testing after proton therapy demonstrate variable changes of different neurocognitive functions. The tests show high degree of patient acceptance. They are feasible with admissible effort and can be initiated in every center opened in order to collect long term data for neurocognitive toxicity.

HYPOTHESIS: Offering a structured practice CT simulation date to pediatric patients ages 4–9 receiving proton therapy reduces the need for daily anesthesia.

BACKGROUND: For pediatric patients undergoing radiation therapy, it is necessary for the patient to receive a CT scan for treatment planning. The scan requires the child to stay motionless, as does daily treatment. Prior to March 2016, there was no formal process for pediatric patients completing a CT simulation at the Northwestern Medicine Chicago Proton Center. For children aged 8 or less, the staff in the CT department would attempt to get the child through the CT simulation without anesthesia on the day of their consultation. If this was unsuccessful, the patient would undergo CT with anesthesia and proceed with daily anesthesia for treatment.

INTERVENTION: A practice CT was established as of January 16th, 2017. This included a pre-call from the child life specialist (CLS) to evaluate the patient and parent needs and expectations. The day of practice CT simulation, time is scheduled for child life to meet with the patient and the parent. The child life specialist used age appropriate explanations and visual aids to guide the patient through what will happen, then worked with the child throughout CT simulation to help them tolerate the procedure. If patient is unable to tolerate the scan after one or two attempts, the patient will complete the CT simulation, as well as daily proton therapy treatment, under anesthesia.

CONCLUSION: Based on pre-screening, 23 out of 46 children aged 4–9 were determined to be viable candidates for receiving an official practice day. Of these 23 children, 22 have successfully completed their CT simulation, and subsequent treatment, without anesthesia. This translates into a 97% success rate. This processes has reduced the treatment burden on the child and family by eliminating the need for daily anesthesia, thus reducing the total treatment time and treatment cost.

BACKGROUND: For the treatment of rectal cancer, pencil beam scanning proton therapy (PBS-PT) may offer a reduction in radiation exposure to normal tissues compared to 3D-conformal photon radiotherapy (3DCRT). The purpose of this study is to report the clinical implementation and dosimetric analysis of pre-operative short-course PBS-PT (25 Gray in 5 fractions) for rectal cancer.

METHODS AND MATERIALS: This was a retrospective review of ten patients with stage IIA-IVB rectal cancer who received pre- operative short-course PBS-PT between 2018 and 2019. Patients received 25 Gy (radiobiological effectiveness =1.1) in 5 fractions on consecutive weekdays immediately preceding curative-intent total mesorectal excision. Patients were treated supine with a full bladder on a foam pad and knee cushion with vacuum mold immobilization of the legs. Plans were generated using Eclipse treatment planning system (Version 13.7, Varian Medical Systems). The clinical target volume (CTV) encompassed the rectal tumor, mesorectum, and regional lymphatics. PBS-PT plans were generated using single-field optimization with 2 posterior-oblique fields. The goal CTV coverage was V100% ≥ 98%. Robust optimization of CTV coverage was performed with positional uncertainty of +/− 5 mm in x, y, and z directions and range uncertainty of +/− 5%. Verification CT scans were performed on the first 3 days of treatment. Each patient had a backup 3DCRT plan with standard 3–4 pelvic fields generated for dosimetric comparison.

RESULTS: CTV coverage was similar between PBS-PT and 3DCRT plans. PBS-PT had significant reductions in dose to the small bowel, large bowel, bladder, and femoral heads. All 10 patients completed PBS-PT as planned without treatment break or need for replanning. All CT verification scans demonstrated good target coverage with CTV V100 > 95%.

CONCLUSION: Pre-operative short-course PBS-PT has been successfully implemented and offers a significant reduction of radiation dose to normal tissues. Prospective studies are warranted to evaluate if dosimetric advantages translate into clinical benefit.

BACKGROUND: A bilateral post-mastectomy patient diagnosed with right breast cancer was treated with a dual-port tissue expander using intensity-modulated proton therapy (IMPT).

METHOD AND MATERIALS: The dual-port tissue expander (Allox2®, SIENTRA, INC., CA) features two metallic ports in different dimensions: one for saline injection and a second for serous fluid drainage. The dual-port was carefully contoured and its density was overridden based on the information provided by the manufacturer (Grade 2 Titanium casing and Neodymium 35EH magnet). Three single-field uniform dose IMPT plans were generated: a. 2-field non-coplanar, b. 3-field coplanar, and c. 3-field non-coplanar beam arrangements. All plans were inverse optimized and forward calculated using the Monte Carlo dose algorithm. Dosimetric comparisons were evaluated to select the optimum plan for patient treatment. Patient setup and treatment time were also recorded.

RESULTS: A dose cold spot was noted behind the dual-port within the tissue expander. A clinical target volume for evaluation was defined for the chest wall after subtracting the ipsilateral tissue expander and cropping 5 mm from the body surface for skin. The volume receiving 95% of the prescribed dose (V95%) was 98.58% in the 3-field non-coplanar plan, compared with 97.68% and 96.25% for the 2-field non-coplanar and 3-field coplanar plans. The dose cold spots behind the dual-port were compensated best with the 3-field non-coplanar beam arrangement. All three beam arrangements resulted in comparable normal tissue doses; ipsilateral lung V20% ranged 15.4–16.4% and heart mean dose ranged 0.81–0.87 Gy(RBE). The patient was treated with the 3-field non-coplanar plan and aligned with dual-port contours for daily IGRT.

CONCLUSIONS: The 3-field non-coplanar plan provided excellent target coverage for a patient with a dual-port tissue expander. Treatment time increased to ~ 30 minutes compared with 15 minutes (one field per fraction) in patients with a single-port tissue expander.

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 dem