BackgroundThis study compares survival rates, recurrence patterns, toxicity, and treatment cost in patients with hepatocellular carcinoma (HCC) treated with either transarterial chemoembolization (TACE) or proton beam radiotherapy (PBT). MethodsSubjects with untreated HCC meeting Milan or San Francisco transplant criteria were recruited. Subjects were randomized to receive PBT (n = 36) or TACE (n = 40). Proton therapy was administered in 15 fractions over 3 weeks to a total dose of 70.2 Gy. TACE was repeated until complete or maximal response. The primary outcome measure was overall survival (OS). Secondary end points were progression-free survival (PFS), local control (LC), toxicity, and cost. ResultsOf the 76 randomized patients, 74 were assessed for outcome measures. The 2-year OS for PBT versus TACE was similar at 68%, 95% confidence interval (CI), 0.54-0.86, and 65%, 95% CI, 0.52-0.83 (p = .80), however, median PFS was improved for PBT versus TACE (not reached vs. 12 months, p = .002). LC was improved with PBT versus TACE (hazard ratio, 5.64; 95% CI, 1.78-17.9, p = .003). Days of posttreatment hospitalization were 24 for PBT and 166 for TACE (p < .001). Total mean cost per patient for treatment and posttreatment care revealed a 28% cost savings for PBT. ConclusionsPBT and TACE yielded similar OS for treatment of HCC, but PFS and LC were improved with PBT compared to TACE. Patients treated with PBT required fewer courses of treatment, fewer posttreatment hospitalization days, and reduced cost of treatment compared to TACE. These data support the use of PBT as a viable treatment alternative to TACE for patients with HCC within transplant criteria.

IMPORTANCE For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. OBJECTIVE To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). DESIGN, SETTING, AND PARTICIPANTS This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy O ncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. EXPOSURES Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. MAIN OUTCOMES AND MEASURES The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. RESULTS The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs <= 39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). CONCLUSIONS AND RELEVANCE Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

In this high-quality database from a prospective phase III clinical trial, cytoplasmic β-catenin and cytoplasmic active β-catenin are statistically significantly associated with OS and DFS and with OS, respectively, independent of other known prognostic factors. In agreement with one previous publication, high levels of cytoplasmic β-catenin, which is transcriptionally silent, were associated with a reduced risk of death. The significant magnitude of these effects makes them clinically relevant, warranting further investigation. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), U24CA196067 (NRG Specimen Bank) from the National Cancer Institute (NCI).

Tumor expression of SMAD4 is significantly associated with better clinical outcome, specifically lower DM and higher DFS and OS, in tumor samples from a large, phase III randomized trial of resectable pancreatic cancer.

PURPOSE:To determine whether a hypofractionated proton therapy regimen will control early-stage disease and maintain low rates of side effects similar to results obtained using standard-fraction proton therapy at our institution.MATERIALS AND METHODS:A cohort of 146 patients with low-risk prostate cancer according to National Comprehensive Cancer Network guidelines (Gleason score <7, prostate-specific antigen [PSA] <10, tumor stage of T1-T2a) received 60 Gy (cobalt Gy equivalent) of proton therapy (20 fractions of 3.0 Gy per fraction) in 4 weeks, a dose biologically equivalent to standard fractionation (44-45 fractions of 1.8 Gy to a total of 79.2 to 81 Gy in 0 weeks). Patients were evaluated at least weekly during treatment, at which time documentation of treatment tolerance and acute reactions was obtained. Follow-up visits were conducted every 3 months for the first 1 years, every 6 months for the next 3 years, then annually. Follow-up visits consisted of history and physical examination, PSA measurements, and evaluation of toxicity.RESULTS:The median follow-up time was 42 months (range, 3-96 months). Acute grade 2 urinary toxicity occurred in 16% (20/120) of the patients; acute grade 2 or higher gastrointestinal toxicity was seen in 1.7% (2/120). At 9 months, 1 patient had late grade 3 urinary toxicity, which resolved by 12 months; no grade 3 gastrointestinal toxicities occurred. The 3-year biochemical survival rate was 99.3% (144/145). The median time to PSA nadir was 30 months.CONCLUSION:Hypofractionated proton therapy of 60 Gy in 20 fractions was safe and effective for patients with low-risk prostate cancer.

Background Because early-stage breast cancer can be treated successfully by a variety of breast-conservation approaches, long-term quality of life (QoL) is an important consideration in assessing treatment outcomes for these patients. This study compares patient-reported QoL outcomes among women with stage 0-2 disease treated via lumpectomy followed by whole breast irradiation (WBI) or partial breast proton irradiation (PBPT). Methods In this cross-sectional study, 129 participants evaluated QoL several years post-treatment by responding to subjective instruments, including established scalar questionnaires and self-report measures. Responses were averaged between the two groups. Results At 6.5 years (median) postdiagnosis, participants' demographic, and clinical characteristics were similar. Patient-reported outcomes were reported as mean scale scores for the two groups, all displaying significant differences favoring PBPT, including: cosmetic breast cancer treatment outcome scale (BCTOS) (PBPT mean 1.45, WBI mean 1.88, P < 0.001); breast pain (PBPT mean 1.30, WBI mean 1.67, P < 0.05); breast texture (BPT mean 1.44, WBI mean 1.91, P < 0.001); clothing fit (PBPT mean 1.06, WBI 1.46, P < 0.001); fatigue (PBPT mean 2.24, WBI mean 3.77, P < 0.002); impact of daily life fatigue on personal relations (OBPT mean 0.83, WBI mean 2.15, P < 0.001); and self-consciousness (appearance dissatisfaction) (PBPT mean 1.38, WBI mean 1.77, P < 0.004). Conclusion Patients' responses suggest that PBPT is associated with improved overall QoL compared to standard whole breast treatment. These self-perceptions are reported by patients who are 5-10 years post-treatment, and that PBPT may enhance QoL in a multitude of interrelated ways.

Background: Biopsy fi ndings of percentage of positive biopsy cores, percentage of cancer volume, and maximum involvement of biopsy cores have been shown to have prognostic value and correlate with magnetic resonance imaging (MRI) fi ndings of extracapsular extension and seminal vesicle invasion.The relationship of these prognostic biopsy factors to MRI fi ndings of the presence of a dominant lesion, has not yet been investigated.Methods: Sixty-fi ve patients with intermediate risk prostate cancer were included in a retrospective cohort.MRI was acquired using either 1.5 Tesla (T) with endorectal coil or a 3 T MRI unit.Findings of extracapsular extension, seminal vesicle invasion, and presence and number of dominant lesions were noted.T-test and Cox regression statistical analyses were performed.Results: Patients with one or more dominant lesions on MRI had a signifi cantly higher mean percentage of positive biopsy cores (56.7% vs 39.8%, p=0.004), percentage of cancer volume (23.5% vs 14.5%, p=0.011) and maximum involvement of biopsy cores (62.9% vs 47.3%, p=0.027) than those without a dominant lesion on MRI.On multivariate analysis, only percentage of positive biopsy cores remained a statistically signifi cant predictor for a dominant lesion on MRI (Hazard Ratio 1.06 [95% CI 1.01-1.12;p=0.02]), whereas prostate-specifi c antigen, clinical T-stage, Gleason score, percentage of cancer volume, and maximum involvement of biopsy cores were not signifi cant predictors of a dominant lesion on MRI.Receiver-operator characteristic analysis was done and a cutoff value of >=50% was chosen for percentage of positive biopsy cores, >=15% for percentage of cancer volume, >=50% for maximum involvement of biopsy cores. Conclusion:Percentage of positive biopsy cores was found to be a signifi cant predictor for the presence of a dominant lesion on MRI.This fi nding is hypothesis-generating and should be confi rmed with a prospective trial.

PURPOSE:This prospective cohort evaluated patients with acoustic neuroma treated with proton irradiation at Loma Linda University Medical Center. A dose of 50.4 Gy in 28 fractions was given to improve hearing preservation while maintaining tumor control.PATIENTS AND METHODS:Ninety-five patients were treated from March 1991 to March 2008. Fractionated proton radiotherapy at daily doses of 1.8 Gy was employed. Patients were treated to 1 of 3 total doses: 59.4 Gy, used initially for patients without serviceable hearing; 54 Gy, used for patients with serviceable hearing through October 2000; and 50.4 Gy used since 2001 for patients with serviceable hearing. Survival and local control were calculated using the Kaplan-Meier method. Logistic regression analysis was preformed comparing dose, tumor size, and tumor location with hearing preservation.RESULTS:Ninety-four patients were assessable; the median follow-up was 64 months. Five-year local control rates for the 59.4 Gy, 54 Gy, and 50.4 Gy groups were 95%, 97%, and 92%, respectively (P = .80); the overall 10-year actuarial control rate was 90%. Cranial nerve injuries occurred in <5% in all groups. Four-year actuarial rates of hearing preservation were maintained in 44% of patients treated with 54 Gy and 64% treated with 50.4 Gy (P = .284). On multivariate analysis, initial tumor diameter (≤1.5 cm) was found to be a prognostic factor for maintaining serviceable hearing in both groups (P = .011).CONCLUSIONS:Fractionated proton therapy of 50.4 Gy offers excellent local control and minimal cranial nerve toxicities. Improved rates of hearing preservation that are comparable with radiosurgery were seen with 50.4 Gy compared with higher doses, although this did not reach significance. Maintaining hearing was found to be associated with smaller initial tumor size.

Purpose: To investigate the long-term effects of vertebral-body-sparing proton craniospinal irradiation (CSI) on the spine of young patients with medulloblastoma. Methods and materials: Six children between the ages of 3 and 5 years with medulloblastoma were treated with vertebral-body-sparing proton CSI after maximal safe resection. Radiation therapy was delivered in the supine position with posterior beams targeting the craniospinal axis, and the proton beam was stopped anterior to the thecal sac. Patients were treated with a dose of either 23.4 Gy or 36 Gy to the craniospinal axis followed by a boost to the posterior fossa and any metastatic lesions. Chemotherapy varied by protocol. Radiographic effects on the spine were evaluated with serial imaging, either with magnetic resonance imaging scans or plain film using Cobb angle calculations, the presence of thoracic lordosis, lumbar vertebral body-to-disc height ratios, and anterior-posterior height ratios. Clinical outcomes were evaluated by patient/family interview and medical chart review. Results: Overall survival and disease free survival were 83% (5/6) at follow-up. Median clinical and radiographic follow-up were 13.6 years and 12.3 years, respectively. Two patients were clinically diagnosed with scoliosis and treated conservatively. At the time of follow-up, no patients had experienced chronic back pain or required spine surgery. No patients were identified to have thoracic lordosis. Diminished growth of the posterior portions of vertebral bodies was identified in all patients, with an average posterior to anterior ratio of 0.88, which was accompanied by compensatory hypertrophy of the posterior intervertebral discs. Conclusion: Vertebral-body-sparing CSI with proton beam did not appear to cause increased severe spinal abnormalities in patients treated at our institution. This approach could be considered in future clinical trials in an effort to reduce toxicity and the risk of secondary malignancy and to improve adult height.

Long-term quality of life (QoL) is a salient factor in assessing outcomes of breast conservation therapy for patients with early-stage breast cancer. This study compares patient-reported QoL outcomes among women with stage 0-II disease treated with partial mastectomy followed by partial-breast proton irradiation (PBPI) or whole-breast photon (WBI). : PBPI subjects were recruited from previous participation in an institutional prospective clinical trial. WBI subjects were recruited from a registry maintained at the same institution. QoL tools completed included the Harvard Cosmesis Scale (HCS), Breast Cancer Treatment Outcome Scale (BCTOS), Brief Fatigue Inventory (BFI), Medical Outcomes Study (MOS) Short Form, and Body Image Scale (BIS). 180 subjects received surveys with 142 being completed and returned yielding a 79% participation rate. 13 were determined to be ineligible due to bilateral disease, disease recurrence, metastatic disease, or other serious medical co-morbidities. 129 participants completed QoL and were included for evaluation, 72 following PBPI and 57 following WBI. Median time from treatment was 7.4 years (PBPI) and 6.3 years (WBI). The two groups were well matched for age, weight, marital status, race, education, employment, recent health status, stage, tumor size, extent of surgery, and use of adjuvant systemic therapy. Significant differences favoring the proton group were seen for several domains. The HCS showed higher cosmetic mean scores for PBPI 3.4 vs WBI 2.4 (p<0.001). BCTOS results showed improved weighted BCTOS (5.5 vs 7.6, p<0.001), cosmetic BCTOS (11.6 vs 15.0, p<0.001), and BS pain (4.2 vs 5.3, p=0.005) for PBPI vs WBI respectively. BFI demonstrated reduced fatigue (2.2 vs 3.8, p=0.002) with less interference with daily general activities (1.7 vs 2.8, p=0.017) for PBPI vs WBI. MOS survey resulted in statistically significant improved perception of general health with improved emotional and social functioning for PBPI. BIS resulted in improved overall score favoring PBPI (12.1 vs 14.2, p=0.009). Patients' responses suggest that partial-breast proton radiotherapy is associated with higher long term overall QoL across multiple domains when compared to a comparable cohort of patients treated with whole breast radiotherapy.

Passively scattered proton therapy (PSPT) has been used for stereotactic body radiation therapy (SBRT) of various sites, including the lung and liver. To our knowledge there is no data for PSPT for spinal SBRT. Therefore, we undertook a dosimetric analysis to evaluate the feasibility of using PSPT with minimal beams for SBRT to treat spine metastases per the ongoing clinical trial RTOG 0631. In 2 model patient simulations, vertebral levels were selected in the cervical, thoracic, and lumbar spine, and clinical target volumes (CTVs) were generated according to the guidelines described in RTOG 0631 to a dose of 18 CGE in 1 fraction. Multiple plans were generated for each CTV using passively scattered proton beams. Plans were evaluated based on the dose coverage of the target volume, the ability to meet dose constraints to surrounding organs at risk, as well as dose homogeneity. RTOG 0631 criteria for target coverage and normal tissue constraints were met for each of the target volumes in the cervical, thoracic, and lumbar spine levels. For upper cervical vertebra, 2 opposed lateral beams were sufficient to achieve dose coverage and meet constraints. The spinal cord received a maximum dose of 13.8 CGE with 0.22 mL receiving 10 CGE, and 2.24 mL of the pharynx received a dose of 10.5 CGE. In the lower cervical, thoracic, and lumbar spine, the shoulders, lungs, and bowel, respectively, impeded the use of lateral beams, and instead 5 beams were required to meet homogeneity and conformity constraints. The 5-beam arrangement included a posterior beam, 2 posterior oblique beams, and 2 posterior oblique patches. For the thoracic target, the spinal cord received a maximum dose of 11.3 CGE with 0.36 mL receiving 10 CGE, and 0.03 mL of the esophagus received 16 CGE. In the lumbar spine, 0.05 mL of the cauda equina received 16 CGE. Distant anterior structures, such as the heart, stomach, and bowel received negligible dose. The treatment of spine metastases per the RTOG 0631 protocol using PSPT is feasible at each spinal level with negligible distant anterior structure dose. For the superior cervical spine we recommend the use of 2 opposed lateral beams, and in the lower cervical, thoracic, and lumbar spine we recommend a 5-beam patch plan using posterior and posterior oblique beams.

Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC).Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization.Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group.Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy. (C) 2016 Elsevier Inc. All rights reserved.

Background: In patients with clinically localized prostate cancer receiving external beam radiation therapy, studies have shown information from prostate biopsy cores can be predictive of clinical outcomes. Recent work from our institution compared several biopsy findings in low- and intermediate-risk patients and found a subset of patients who were more likely to fail treatment. This indicates patients in these groups may benefit from further risk stratification prior to initiation of therapy. Furthermore, findings on pre-treatment prostate MRI independently predict PSA relapse after external beam radiation therapy. Comparing MRI and pathological data may help to accurately further risk stratify patients. Our purpose is to determine if there is a correlation between the poor prognostic factors demonstrated on prostate biopsy cores and selected findings on prostate MRI. Methods: Intermediate risk prostate cancer patients with 1.5 and 3.0 Tesla MRI scans of the prostate performed from 2007-2011 were selected for a retrospective cohort study. Cases were reviewed by two body-trained radiologists who were blinded to clinical patient information. Reader consensus was obtained at the time of reading regarding presence of extracapsular extension, seminal vesicle invasion, and disease in each sextant by T2 and ADC imaging, including a dominant nodule. Results were analyzed for correlation between these findings on MRI and compared with results of prostate biopsy cores, including maximum involvement of any biopsy core (MIBC), percentage of cancer volume (PCV) and percent positive biopsy cores (PPBC). Results: The absolute presence of a dominant nodule on MRI was statistically significantly correlated with elevated PCV and PPBC applying the t-test for equality of means, with p-values of 0.019 and 0.006 respectively. PSA, Gleason score, and MIBC were not found to be correlated with dominant nodule on MRI. Conclusions: There is a strong positive correlation between MRI findings of a dominant nodule and prognostic biopsy findings of elevated PPBC and PCV.

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (< vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose < 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose < 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]

validate this finding and will permit correlation with clinical outcome measures.

BACKGROUND:Exploiting biologic imaging, studies have been performed to boost dose to gross intraprostatic tumor volumes (GTV) while reducing dose elsewhere in the prostate. Interest in proton beams has increased due to superior normal-tissue sparing they afford. Our goal was to dosimetrically compare 3D conformal proton boost plans with intensity-modulated radiation therapy (IMRT) plans with respect to target coverage and avoiding organs at risk.METHODS:Treatment planning computer tomography scans of ten patients were selected. For each patient, two hypothetical but realistic GTVs each with a fixed volume were contoured in different anatomical locations of the prostate. IMRT and proton beam plans were created with a prescribed dose of 50.4 Gy to the initial planning target volume (PTV) including the PTV of the seminal vesicles (PSV), 70.2 Gy to the PTV of the prostate (PPS), and 90 Gy to the PTV of the gross tumor volumes (PGTVs). For proton plans, uncertainties of range and patient setup were accounted for; apertures were adjusted until the dose-volume coverage of PTVs matched that of the IMRT plan. For both plans, prescribed PTV doses were made identical to allow for comparing normal-tissue doses.RESULTS:Protons delivered more homogeneous but less conformal doses to PGTVs than IMRT did and comparable doses to PSV and PPS. Volumes of bladder and rectum receiving doses higher than 65 Gy were similar for both plans. However, volumes receiving less than 65 Gy were significantly reduced, i.e., protons reduced integral dose by 45.6 % and 26.5 % for rectum and bladder, respectively. This volume-sparing was also seen in femoral heads and penile bulb.CONCLUSIONS:Protons delivered comparable doses to targets in dose homogeneity and conformity and spared normal tissues from intermediate-to-low doses better than IMRT did. Further improvement of dose sparing and changes in homogeneity and conformity may be achieved by reducing proton range uncertainties and from implementing intensity modulation.

Proton therapy through the use of the Bragg peak affords clinicians a tool with which highly conformal dose can be delivered to the target while minimizing integral dose to surrounding healthy tissue. To gain maximum benefit from proton therapy adequate patient immobilization must be maintained to ensure accurate dose delivery. While immobilization in external beam radiation therapy is designed to minimize inter- and intra-fraction target motion, in proton therapy there are other additional aspects which must be considered, chief of which is accurately determining and maintaining the targets water-equivalent depth along the beam axis. Over the past 23 years of treating with protons, the team at the James M. Slater Proton Treatment and Research Center at Loma Linda University Medical Center have developed and implemented extensive immobilization systems to address the specific needs of protons. In this publication we review the immobilization systems that are used at Loma Linda in the treatment of head and neck, prostate, upper GI, lung and breast disease, along with a description of the intracranial radiosurgery immobilization system used in the treatment of brain metastasis and arteriovenous malformations (AVM’s).

Purpose:To check the overall accuracy of proton radiosurgery treatment delivery using ready‐made circular collimator inserts and fixed thickness compensating boluses.Methods:Lucy 3D QA phantom (Standard Imaging Inc. WI, USA) inserted with GaFchromicTM film was irradiated with laterally scattered and longitudinally spread‐out 126.8 MeV proton beams. The tests followed every step in the proton radiosurgery treatment delivery process: CT scan (GE Lightspeed VCT), target contouring, treatment planning (Odyssey 5.0, Optivus, CA), portal calibration, target localization using robotic couch with image guidance and dose delivery at planned gantry angles. A 2 cm diameter collimator insert in a 4 cm diameter radiosurgery cone and a 1.2 cm thick compensating flat bolus were used for all beams. Film dosimetry (RIT114 v5.0, Radiological Imaging Technology, CO, USA) was used to evaluate the accuracy of target localization and relative dose distributions compared to those calculated by the treatment planning system.Results:The localization accuracy was estimated by analyzing the GaFchromic films irradiated at gantry 0, 90 and 270 degrees. We observed 0.5 mm shift in lateral direction (patient left), ±0.9 mm shift in AP direction and ±1.0 mm shift in vertical direction (gantry dependent). The isodose overlays showed good agreement (<2mm, 50% isodose lines) between measured and calculated doses.Conclusion:Localization accuracy depends on gantry sag, CT resolution and distortion, DRRs from treatment planning computer, localization accuracy of image guidance system, fabrication of ready‐made aperture and cone housing. The total deviation from the isocenter was 1.4 mm. Dose distribution uncertainty comes from distal end error due to bolus and CT density, in addition to localization error. The planned dose distribution was well matched (>90%) to the measured values 2%/2mm criteria. Our test showed the robustness of our proton radiosurgery treatment delivery system using ready‐made collimator inserts and fixed thickness compensating boluses.

Purpose: To evaluate the use of standard apertures and range shifters for the treatment of brain metastasis in proton stereotactic radiosurgery. Methods: Five localized brain metastasis patients previously treated using our intracranial proton stereotactic radiosurgery procedure (i.e. with a custom aperture and bolus), were randomly selected from our patient cohort. The custom aperture and bolus treatment plans were used as the standard of care in this case and comparative treatment plans using the standard aperture and range shifter concept were generated. Gantry/table angle and the number of treatment beams were optimized as part of this study to evaluate the ability of the standard aperture/range shifter system to deliver a comparable treatment to the patient. Conformity index, homogeneity index, isodose volumes and integral dose were all evaluated to determine the degree of conformity of the plans created and for comparison to the custom aperture/bolus treatment modality. Results: The generated treatment plans demonstrated that the standard aperture and range shifter combination could be used to produce comparable conformity index and isodose volumes to the custom aperture/bolus case in four out of the five patients studied. In two of the patients a comparative conformity index was achieved by optimizing the angles of the 3 treatment beams, while in two of the cases 1 or 2 additional beams were required. Additionally, this system exhibited efficiency gains of 60-90% over the custom aperture bolus system in reducing the time necessary for treatment planning, device manufacture and QA. Conclusion: This work demonstrated that largely spherical shape of brain metastasis makes this target well suited to an application of standard apertures, while additionally providing efficiency gains in device manufacture and QA for treatment.

Purpose: To determine the proton output factors for an SRS cone set using standardized apertures and varied range compensators (bolus blanks); specifically, to determine the best method for modeling the bolus gap factor (BGF) and eliminate the need for patient specific calibrations. Methods: A Standard Imaging A-16 chamber was placed in a Plastic Water phantom to measure the change in dose/MU with different treatment combinations for a proton SRS cone, using standardized apertures and range compensators. Measurements were made with all apertures in the SRS cone set, with four different range compensator thicknesses and five different air gaps between the end of the SRS cone and the surface of the phantom. The chamber was located at iso-center and maintained at a constant depth at the center of modulation for all measurements. Each aperture was placed in the cone to measure the change in MU needed to maintain constant dose at the chamber, as the air gap was increased with different thicknesses of bolus. Results: The dose/MU varied significantly with decreasing aperture size, increasing bolus thickness, or increasing air gap. The measured data was fitted with the lowest order polynomials that accurately described the data, to create a model for determining the change in output for any potential combination of devices used to treat a patient. For a given standardized aperture, the BGF could be described by its constituent factors: the bolus thickness factor (BTF) and the nozzle extension factor (NEF). Conclusion: The methods used to model the dose at the calibration point could be used to accurately predict the change in output for SRS proton beams due to the BGF, eliminating the need for patient specific calibrations. This method for modeling SRS treatments could also be applied to model other treatments using passively scattered proton beams.