PURPOSE:To compare outcomes, liver toxicity, and survival between patients with hepatocellular carcinoma treated with hypofractionaed image-guided radiation therapy (HIGRT) delivered in 5 versus 10 fractions within a Veterans Affairs (VA) population. METHODS AND MATERIALS:A retrospective review was performed of patients with unresectable or medically inoperable hepatocellular carcinoma treated with HIGRT at the Durham VA Medical Center between 2013 and 2024. Patients treated with palliative intent or lacking follow-up were excluded. The standard regimen was 50 Gy in 5 fractions; 50 Gy in 10 fractions was used when organ-at-risk constraints precluded 5-fraction delivery. Demographic, clinical, and dosimetric data were extracted from the VA National Corporate Data Warehouse. Outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS:Among 147 patients (median age, 67 years), 96 received 50 Gy in 5 fractions and 51 received 50 Gy in 10 fractions. Most patients had cirrhosis (93.9%) and Child-Pugh class A liver function (82.3%). Tumors were larger in the 10-fraction cohort (median, 35 cm3 vs 14 cm3; P < .001). Treatment was well tolerated, with only 1 grade 3 event and no grade ≥4 toxicity. The cumulative grade ≥2 toxicity was similar between regimens (hazard ratio, 1.59; P = .25). Worsening of Child-Pugh score by ≥2 points occurred more frequently with 10 fractions (hazard ratio 2.15; P < .01), but this was associated only with higher mean liver dose in a multivariate model. Two-year local control was 90.7% for 5 fractions and 82.4% for 10 fractions; this difference was not significant after adjusting for tumor size. Median overall survival was 2.8 years, shorter in the 10-fraction cohort due to poorer baseline characteristics. CONCLUSIONS:Both 50 Gy in 5 and 10 fractions achieved excellent local control and minimal toxicity. The 10-fraction regimen is a safe, effective alternative when normal tissue constraints preclude 5-fraction HIGRT.

Background/Objectives: Hypofractionated ablative radiation is an increasingly popular option for patients with hepatocellular carcinoma (HCC). However, concern remains about the risk for radiation-induced liver toxicity in patients with decompensated liver function. Methods: We retrospectively identified patients with underlying Child-Pugh (CP) B or C liver function treated at our University and Veterans Affairs (VA) departments from 2014 to 2019. Primary endpoints included treatment-related toxicity and dosimetric parameters. Results: 38 patients were included in the analysis. Most patients (98%) had CP B or Albumin-Bilirubin (ALBI) grade 2-3 (100%) liver disease. The median dose was 50 Gy (range 30-50) delivered in 5 or 10 fractions. Most patients had a single tumor treated (66%) with a median size of 3.1 cm (Interquartile Range (IQR) 2.3-4.1). The mean liver dose was 9.28 Gy (IQR 6.76-13.64) with a liver D800cc of 3.99 Gy (IQR 1.41-8.02). All patients completed their intended course with a median follow-up of 43 months. Four patients (10.3%) developed non-classical radiation-induced liver disease (RILD), comparable to the rate for patients with CP A function treated contemporaneously (8.3%). Otherwise, one patient (2.6%) experienced acute grade 3+ (non-RILD) hepatobiliary toxicity, while one patient (2.6%) experienced late grade 3+ hepatobiliary toxicity. Local control was promising with 2-year freedom from progression in the treated lesion of 73% (95% CI 38-91%). Median overall survival was 12 months (95% CI 5-25 months). Conclusions: Ablative radiation for patients with decompensated liver function and HCC appears well tolerated with low rates of RILD and encouraging local control. With careful selection, these patients should be considered for inclusion in future randomized trials.

Despite continuous advancements in cancer treatment, brain metastatic disease remains a significant complication of primary cancer and is associated with an unfavorable prognosis. One approach for improving diagnosis, management, and outcomes is to implement algorithms based on artificial intelligence for the automated segmentation of both pre- and post-treatment MRI brain images. Such algorithms rely on volumetric criteria for lesion identification and treatment response assessment, which are still not available in clinical practice. Therefore, it is critical to establish tools for rapid volumetric segmentations methods that can be translated to clinical practice and that are trained on high quality annotated data. The BraTS-METS 2025 Lighthouse Challenge aims to address this critical need by establishing inter-rater and intra-rater variability in dataset annotation by generating high quality annotated datasets from four individual instances of segmentation by neuroradiologists while being recorded on video (two instances doing "from scratch" and two instances after AI pre-segmentation). This high-quality annotated dataset will be used for testing phase in 2025 Lighthouse challenge and will be publicly released at the completion of the challenge. The 2025 Lighthouse challenge will also release the 2023 and 2024 segmented datasets that were annotated using an established pipeline of pre-segmentation, student annotation, two neuroradiologists checking, and one neuroradiologist finalizing the process. It builds upon its previous edition by including post-treatment cases in the dataset. Using these high-quality annotated datasets, the 2025 Lighthouse challenge plans to test benchmark algorithms for automated segmentation of pre-and post-treatment brain metastases (BM), trained on diverse and multi-institutional datasets of MRI images obtained from patients with brain metastases.

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps.

Purpose During stereotactic radiosurgery (SRS) planning for brain metastases (BM), brain MRIs are reviewed to select appropriate targets based on radiographic characteristics. Some BM are difficult to detect and/or definitively identify and may go untreated initially, only to become apparent on future imaging. We hypothesized that in patients receiving multiple courses of SRS, reviewing the initial planning MRI would reveal early evidence of lesions that developed into metastases requiring SRS. Methods Patients undergoing two or more courses of SRS to BM within 6 months between 2016 and 2018 were included in this single-institution, retrospective study. Brain MRIs from the initial course were reviewed for lesions at the same location as subsequently treated metastases; if present, this lesion was classified as a “retrospectively identified metastasis” or RIM. RIMs were subcategorized as meeting or not meeting diagnostic imaging criteria for BM (+ DC or -DC, respectively). Results Among 683 patients undergoing 923 SRS courses, 98 patients met inclusion criteria. There were 115 repeat courses of SRS, with 345 treated metastases in the subsequent course, 128 of which were associated with RIMs found in a prior MRI. 58% of RIMs were + DC. 17 (15%) of subsequent courses consisted solely of metastases associated with + DC RIMs. Conclusion Radiographic evidence of brain metastases requiring future treatment was occasionally present on brain MRIs from prior SRS treatments. Most RIMs were + DC, and some subsequent SRS courses treated only + DC RIMs. These findings suggest enhanced BM detection might enable earlier treatment and reduce the need for additional SRS.

Meningiomas are the most common primary intracranial tumor in adults and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on multiparametric MRI (mpMRI) for diagnosis, treatment planning, and longitudinal treatment monitoring; yet automated, objective, and quantitative tools for non-invasive assessment of meningiomas on mpMRI are lacking. The BraTS meningioma 2023 challenge will provide a community standard and benchmark for state-of-the-art automated intracranial meningioma segmentation models based on the largest expert annotated multilabel meningioma mpMRI dataset to date. Challenge competitors will develop automated segmentation models to predict three distinct meningioma sub-regions on MRI including enhancing tumor, non-enhancing tumor core, and surrounding nonenhancing T2/FLAIR hyperintensity. Models will be evaluated on separate validation and held-out test datasets using standardized metrics utilized across the BraTS 2023 series of challenges including the Dice similarity coefficient and Hausdorff distance. The models developed during the course of this challenge will aid in incorporation of automated meningioma MRI segmentation into clinical practice, which will ultimately improve care of patients with meningioma.

Abstract BACKGROUND Most patients with isocitrate dehydrogenase mutant (IDHm) low-grade glioma (LGG) undergo active MRI surveillance after initial surgery. Timely biopsy referral during surveillance is a complex trade-off between avoiding the harms of unnecessary surgery and early detection of transformation. Serial surveillance MRIs could be leveraged to develop dynamic imaging markers, yet prior research has primarily focused on the prognostication of pre-treatment images. We piloted the feasibility of an automated pipeline using patient-specific imaging trajectories. METHODS We retrospectively identified 12 progressive IDHm LGG patients and collected serial surveillance MRIs. A previously developed segmentation model was fine-tuned on a subset of T2/FLAIR images (n=49) before automated tumor segmentation was performed on all MRIs. We extracted geometric and topological tumor features, including volume, cross product, and Euler Characteristic Transform, from each MRI. We used piecewise linear regression to quantify feature trajectories and identify change points in feature growth rates. RESULTS Twelve patients received 14 biopsies/repeat resections (10 with transformation, 4 without) and 282 MRIs (median per patient: 17, range: 10-40). All biopsies/repeat resections were preceded by a change point in tumor volume trajectory, indicating an increase in tumor growth rate preceding clinician-determined MRI progression and biopsy referral. The mean increase in volume growth rate, pre to post change point, was 2.3cm3/month (SE: 0.9) in biopsies/repeat resections with transformation, compared to 1.1cm3/month (SE: 0.6) in biopsies/repeat resections without transformation. Among the ten patients with transformation, the median time from IDHm LGG diagnosis to transformation was 64.8 months (range: 38.6-141.1), and the median time between volume change point and transformation was 15.6 months (range: 4.6-28.2). DISCUSSION This pilot study suggests that feature trajectories from serial MRIs of IDHm LGG patients may advance the detection and treatment of transformed lesions by 12-18 months. Larger studies can corroborate these findings and inform clinical decision-making.

Purpose: We sought to develop a computer-aided detection (CAD) system that optimally augments human performance, excelling especially at identifying small inconspicuous brain metastases (BMs), by training a convolutional neural network on a unique magnetic resonance imaging (MRI) data set containing subtle BMs that were not detected prospectively during routine clinical care.Methods and Materials: Patients receiving stereotactic radiosurgery (SRS) for BMs at our institution from 2016 to 2018 with-out prior brain-directed therapy or small cell histology were eligible. For patients who underwent 2 consecutive courses of SRS, treatment planning MRIs from their initial course were reviewed for radiographic evidence of an emerging metastasis at the same location as metastases treated in their second SRS course. If present, these previously unidentified lesions were contoured and categorized as retrospectively identified metastases (RIMs). RIMs were further subcategorized according to whether they did (+DC) or did not (-DC) meet diagnostic imaging-based criteria to definitively classify them as metastases based upon their appearance in the initial MRI alone. Prospectively identified metastases (PIMs) from these patients, and from patients who only underwent a single course of SRS, were also included. An open-source convolutional neural network architecture was adapted and trained to detect both RIMs and PIMs on thin-slice, contrast-enhanced, spoiled gradient echo MRIs. Patients were randomized into 5 groups: 4 for training/cross-validation and 1 for testing.Results: One hundred thirty-five patients with 563 metastases, including 72 RIMS, met criteria. For the test group, CAD sensi-tivity was 94% for PIMs, 80% for +DC RIMs, and 79% for PIMs and +DC RIMs with diameter <3 mm, with a median of 2 false positives per patient and a Dice coefficient of 0.79.Conclusions: Our CAD model, trained on a novel data set and using a single common MR sequence, demonstrated high sen-sitivity and specificity overall, outperforming published CAD results for small metastases and RIMs - the lesion types most in need of human performance augmentation. (c) 2022 Elsevier Inc. All rights reserved.

BackgroundModerately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer; however, limited MHRT data address high-risk prostate cancer (HRPC) and/or African American patients. We report clinical outcomes and toxicity profiles for individuals with HRPC treated in an equal access system.MethodsWe identified patients with HRPC treated with MHRT at a US Department of Veterans Affairs referral center. Exclusion criteria included < 12 months follow-up and elective nodal irradiation. MHRT included 70 Gy over 28 fractions or 60 Gy over 20 fractions. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were graded using Common Terminology Criteria for Adverse Events, version 5.0. Clinical endpoints, including biochemical recurrence-free survival (BRFS), distant metastases-free survival (DMFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using Kaplan-Meier methods. Clinical outcomes, acute toxicity, and late toxicity-free survival were compared between African American and White patients with logistic regression and log-rank testing.ResultsBetween November 2008 and August 2018, 143 patients with HRPC were treated with MHRT and followed for a median of 38.5 months; 82 (57%) were African American and 61 were White patients. Concurrent androgen deprivation therapy (ADT) was provided for 138 (97%) patients for a median duration of 24 months. No significant differences between African American and White patients were observed for 5-year OS (73% [95% CI, 58%-83%] vs 77% [95% CI, 60%-97%]; P = .55), PCSS (90% [95% CI, 79%-95%] vs 87% [95 % CI, 70%-95%]; P = .57), DMFS (91% [95% CI, 80%-96%] vs 81% [95% CI, 62%-91%]; P = .55), or BRFS (83% [95% CI, 70%-91%] vs 71% [95% CI, 53%-82%]; P = .57), respectively. Rates of acute grade 3+ GU and GI were low overall (4% and 1%, respectively). Late toxicities were similarly favorable with no significant differences by race.ConclusionsIndividuals with HRPC treated with MHRT in an equal access setting demonstrated favorable clinical outcomes that did not differ by race, alongside acceptable rates of acute and late toxicities.

Purpose/Objective(s)Brain MRIs are carefully reviewed during the process of stereotactic radiosurgery (SRS) planning to select targets with radiographic characteristics typical of brain metastases (BM). Some BMs, especially ones that are small, dural-based, appear similar to blood vessels or resemble microinfarcts, are difficult to definitively identify and may go untreated initially, only to become apparent on future imaging. We hypothesized that in patients receiving multiple courses of SRS, retrospective review of the initial planning MRI would reveal early evidence of lesions that would subsequently develop into metastases requiring SRS.Materials/MethodsPatients undergoing two or more courses of SRS to BMs within a 6-month interval between 2016 and 2018 were included in this single-institution, retrospective study. Exclusion criteria included small cell histology or previous whole-brain radiation therapy. Brain MRIs from the initial treatment course were reviewed for the presence of a contrast enhancing lesion at the same location as a lesion treated in a subsequent course of SRS, which was classified as a "retrospectively identified metastasis" or RIM.ResultsOf the 683 patients who underwent 923 courses of SRS within the study period, 98 patients met inclusion criteria. There were 120 repeat courses of SRS, with 345 treated metastases in the subsequent course, 128 of which were RIMs. 48% were within 5mm of the dura: 12% were abutting blood vessels: 8% became symptomatic. 23% of subsequent courses consisted of metastases that were all identified as RIMs.ConclusionRadiographic evidence of lesions requiring future treatment was occasionally present on brain MRIs from prior SRS treatments. RIMs are typically small, often abut blood vessels and/or the dura, and rarely become symptomatic. In some patients undergoing SRS, RIMs alone were treated, suggesting that enhanced detection of RIMs could reduce the need for additional courses of SRS.

Purpose:To evaluate the effect of prostate volume on outcomes after moderately hypofractionated radiation therapy (mHFRT) for prostate cancer. Methods and Materials:Prostate cancer patients treated with mHFRT at a Veteran's Affairs Medical Center from August 20, 2008, to January 31, 2018, were identified. Patients were placed into a large prostate planning target volume (LPTV) cohort if their prostate PTV was in the highest quartile. Acute/late genitourinary (GU) and gastrointestinal toxicity events among patients with and without LPTV were compared. Multivariable analyses estimated the effect of factors on toxicity. Overall survival, biochemical recurrence-free survival, and freedom from late GU/gastrointestinal toxicity of patients with and without LPTV were estimated via Kaplan-Meier. Results:Four hundred and seventy-two patients were included. Ninety-three percent received 70 Gy in 2.5 Gy fractions; 75% received androgen deprivation therapy. Median follow-up was 69 months. Patients with LPTV (PTV >138.4 cm3) had a higher late 2 + GU toxicity compared with those without (59% vs 48%, P = .03). Earlier time to late 2 + GU toxicity was associated with LPTV (hazard ratio 1.36; 95% confidence interval [CI], 1.00-1.86; P = .047), androgen deprivation therapy use (hazard ratio 1.60; 95% CI, 1.13-2.27; P = .01), and higher baseline American Urologic Association symptom score (odds ratio 1.03; 95% CI, 1.02-1.05; P < .001). At 2 years, freedom from late 2 + GU toxicity was 46% (95% CI, 47%-54%) for those with LPTV versus 61% (95% CI, 55%-65%) for those without (P = .04). Late grade 3 GU toxicity was 7% for those with LPTV and 4% for those without. No differences in overall survival or biochemical recurrence-free survival were observed between patients with or without LPTV. Conclusions:LPTV did not affect efficacy of mHFRT for prostate cancer; however, it was associated with increased risk and earlier onset of late grade 2 + GU toxicity.

In this multi-institutional analysis of 1139 early-stage PC patients treated with moderately hypofractionated IMRT or PBT, risk of serious late GU and GI complications was low for both treatment groups. Analysis of the dosimetric variables identified an association of Grade 3+ GU toxicity with low-dose radiation exposure of the bladder. Grade 3+ GI toxicity was unrelated to dosimetric variables. PBT plans yielded less exposure of non-target organs to lower-dose radiation while IMRT plans yielded less exposure of non-target organs to higher-dose radiation.

PURPOSE:Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT. METHODS AND MATERIALS:This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only). RESULTS:A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008). CONCLUSIONS:In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.

Moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer; however, there are limited data addressing the use of MHRT in unfavorable high-risk prostate cancer (HRPC) and/or African American patients. We report the clinical outcomes and toxicity profiles for men with HRPC treated in an equal access system comparing endpoints across race. Men with HRPC treated with MHRT at a Veterans' Affairs referral center were identified. Exclusion criteria included <12 months of follow up and elective nodal irradiation. MHRT included 70Gy at 2.5Gy/fx or 60Gy at 3Gy/fx. Demographics, clinical endpoints, and toxicity data were retrospectively obtained. Acute and late (defined as ≥3 months following completion of MHRT) gastrointestinal (GI) and genitourinary (GU) toxicities were graded using CTCAE, version 5.0. Clinical endpoints including biochemical recurrence-free survival (BRFS; per Phoenix criteria), distant metastases-free survival (DMFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated via the Kaplan Meier method. Clinical outcomes, acute toxicity, and late toxicity-free survival were compared between African American (AA) and Caucasian (C) men with logistic regression and log rank testing. 100 HRPC patients were treated with MHRT between 11/2008-8/2018. Mean age was 65.7 years (range, 36-80 years). Median follow up was 64.2 months (IQR 37.2 – 86.3 months). 53 patients were African American (AA), 46 Caucasian (C), and 1 of unknown race. 84 men had unfavorable high-risk disease. T stages included T1c (52), T2 (33), and T3 (15). Median PSA was 16.48 (IQR 8.45 – 35.25). 97 men received concurrent ADT typically starting 6-8 weeks before MHRT, for a median duration of 24 months (IQR 23.3 – 32.8). 97 men received 70Gy at 2.5Gy/fx and 3 men received 60Gy at 3Gy/fx. Clinical outcomes are shown below, with no significant differences between AA and C men. Acute toxicity included GU grade 0 (32), grade 1 (20) and grade 2 (48) and GI grade 0 (89), grade 1 (9), and grade 2 (2). There were no grade 3+ GU or GI acute toxicities. Late toxicities included GU grade 0 (31), grade 1 (10), grade 2 (54), and grade 3 (5), and GI grade 0 (74), grade 1 (13), grade 2 (11), grade 3 (1), and grade 4 (1). Men with HRPC treated with MHRT in an equal access setting demonstrated favorable clinical outcomes with acceptable rates of acute and late toxicities. Clinical outcomes were not significantly different between African American and Caucasian men.Tabled 1Abstract 2940; TableBRFSDMFSOSPCSS5-year median (95% CI)78.7 (69.5 - 87.9)87.0 (79.3 - 94.7)77.2 (68.1 – 86.3)93.1 (87.2 – 99.0)8-year median (95% CI)65.0 (51.0 - 79.0)78.7 (68.1 - 89.3)54.3 (40.0 - 68.6)80.4 (68.3 – 92.5)Race, African American (HR; 95% CI)0.99 (0.65 – 1.52)0.80 (0.46 – 1.35)0.91 (0.64 – 1.28)0.92 (0.48 – 1.74) Open table in a new tab

Moderately hypofractionated radiation therapy (MHRT) is an accepted standard of care for patients with intact low and intermediate risk prostate cancer. Proton beam therapy for prostate cancer offers certain dosimetric advantages, but data directly comparing MHRT modalities are lacking. We aim to compare late toxicity profiles of localized prostate cancer patients treated with proton and photon MHRT. Prospectively-collected institutional databases from 7 tertiary referral centers were queried for patients with intact low or intermediate risk prostate cancer treated from 1998 to 2018 with MHRT, defined as 2.4 – 4.0 Gy per daily fraction given over 4-6 weeks. Patients were stratified based on receipt of proton or photon MHRT. Primary outcomes were late Grade 3+ GU and late Grade 2+ GI toxicity, per CTCAE v4.0, scored by treating institution. Late toxicity was defined as occurring >3 months after treatment completion. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, NCCN risk group, age, pretreatment IPSS (GU only) and anti-coagulant use (GI only). Odds ratios and significance were assessed using generalized linear mixed effects models, with random effects by site. A total of 1850 patients (1282 photon and 568 proton) were included with 1 year minimum follow up. The cohorts were similar in risk group and T stage. However, the photon group had significantly higher baseline IPSS (median 10 vs 7), anti-coagulant use (32.6% vs 15.3%), performance status (28% vs 6% ECOG 1+), PSA (7.6 vs 6.1), and percentage of patients with Gleason 6 disease (66% vs 57%). Late toxicity rates and odds ratios are described in the table below. The most common late toxicities were urinary frequency and rectal bleeding in the proton group and cystitis and rectal bleeding in the photon group. On adjusted analysis for late toxicity, no factors were significantly predictive of GU toxicity and only anti-coagulant use was significantly predictive of GI toxicity (OR 1.88, 95% CI 1.19-2.99). In this large, multi-institutional dataset analysis, rates of late GU and GI toxicity were low with both proton and photon MHRT. No statistically significant difference was seen in late GU toxicity rates. Higher rates of late GI toxicity were found with proton MHRT, but this difference lost statistical significance when adjusted for covariates. Overall, both proton and photon MHRT appear to be safe treatment approaches for low and intermediate risk prostate cancer patients.Abstracts 4058; TableLate Toxicity TypeProton MHRT Toxicity RatePhoton MHRT Toxicity RateOdds Ratio (Confidence Interval)G3+ GUUnadjusted1.6%3.7%0.45 (0.16-1.28)Adjusted2.0%3.9%0.47 (0.17-1.28)G2+ GIUnadjusted11.1%4.8%2.71 (1.17-6.26)Adjusted14.6%4.7%2.69 (0.80-9.05) Open table in a new tab

Moderately hypofractionated radiation therapy (mHFRT) is an accepted standard for treating localized prostate cancer. The toxicity of mHFRT is unknown in men with large prostate volume (LPV), questioning the utility of mHFRT in this scenario. We report efficacy and acute genitourinary (GU) and gastrointestinal (GI) toxicity in men treated with mHFRT according to PV. Localized prostate cancer patients treated with mHFRT at a single Veteran’s Affairs Medical Center from 8/20/08-1/31/18 were identified. Patient, tumor, treatment, and dosimetric variables were recorded. Patients were placed into an LPV cohort if their simulation PV was in the highest quartile. Acute GU and GI toxicities were defined according to the CTCAE v 5.0. Biochemical recurrence free survival (BRFS) (defined as nadir + 2 ng/ml or initiation of salvage ADT) and overall survival (OS) were estimated using the Kaplan Meier method. Univariate logistic regression and Cox proportional hazards modeling estimated the effects of PV on clinical endpoints. 392 men with low (11%), intermediate (63%), and high risk (26%) prostate cancer were treated with mHFRT. Median age was 64 (range 36-80). Median follow up was 68 months (IQR 45.7 – 89.9). Most men (n = 388) received 70 Gy in 2.5 Gy fractions, and 73% received ADT. Median PV was 45.0 cc (IQR 35.1 cc - 60.0 cc). The LPV cohort was defined as > 60 cc (n = 98). The overall rates of 5-year BRFS and OS were 86.8% (95% CI 83.1%– 90.5%) and 83.0% (95% CI 78.9% – 87.1%), respectively. The rates of 5-year BRFS and OS for the LPV cohort were 86.8% (95% CI 83.0%– 90.6%) and 83.3% (95% CI 79.2% – 87.3%). 44% had acute G2+ GU toxicity and 3.8% had acute G2+ GI toxicity. Only 6 experienced acute G3 GU toxicity and 1 acute G3 GI toxicity. Men with PV > 60 cc had similar rates of acute G2+ GU toxicity (OR 0.90 (95% CI 0.57-1.42), p = 0.65) and G2+ GI toxicity (OR 0.73 (95% CI 0.20-2.65), p = 0.63) compared to those with PV < 60 cc. 52% and 7.9% of men had late G2+ GU and late G2+ GI toxicity, respectively. 14 and 6 experienced late G3 GU and G3+ GI toxicity, respectively. Men with PV > 60 cc had similar time to development of late G2+ GU toxicity (HR 1.13 (95% CI 0.96 – 1.31), p = 0.13) and G2+ GI toxicity (HR 0.75 (95% CI 0.43 – 1.15, p = 0.20) compared to those with PV < 60 cc. mHFRT for prostate cancer was well-tolerated among men with PV > 60 cc with high rates of BRFS and OS. Despite higher volumes of bladder and rectal irradiation, men with PV > 60 cc did not have increased rates of acute or late GI/GU toxicity.Abstract 4081; TableVolume, Mean (95% CI)2-sided t-testPV > 60 ccPV < 60 ccp valueBladder V70 (cc)5.19 (4.49 - 5.90)3.21 (2.92 - 3.49)<0.0001Bladder V50 (cc)42.49 (39.31 - 45.66)31.64 (30.08 - 33.20)<0.0001Rectum V50 (cc)18.5 (17.16 - 19.92)14.30 (13.60 – 15.00)<0.0001Rectum V31 (cc)50.67 (47.19 - 54.15)40.56 (38.88 - 42.24)<0.0001 Open table in a new tab