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Brain metastases (BM) from germ cell tumors (GCT) are a poor-prognostic feature. Nonetheless, many patients relapsing with GCT BM achieve long-term disease control after salvage therapy, which often combines radiotherapy (RT) and chemotherapy (CT). Historically, whole brain RT (WBRT) has been the standard RT approach to GCT BM. For patients with a limited burden of GCT BM, stereotactic radiosurgery (SRS) is an attractive alternative for preservation of cognitive function. However, minimal data are available to guide the optimal use of SRS. We report our institutional radiotherapeutic outcomes for GCT BM, with a focus on WBRT and SRS alone. Male patients with extracranial GCT who received WBRT, with or without SRS boost, or SRS alone for BM relapse between 2005 and 2023 were included. Primary outcomes were overall survival (OS) and intracranial progression (IP) from RT completion. Local progression (LP) and radionecrosis (RN) after SRS were assessed per BM treated with SRS. Associations with outcomes were modeled with Cox regression and competing risk regression, accounting for death. Fifty-nine patients were included. Median age at BM diagnosis was 28 years. Thirty-two patients received WBRT. The median WBRT prescription was 30 Gy in 10 fractions. Twenty-seven patients received SRS to 53 BM. The median SRS prescription was 27 Gy in 3 fractions. Patients who received SRS had fewer BM than those who received WBRT (median 1 vs. 3, P = 0.09). Patterns of RT use in conjunction with CT included: RT with no concurrent CT (19 patients, 8 SRS), RT with concurrent conventional-dose CT (17 patients, 6 SRS), RT with concurrent high-dose CT (13 patients, 7 SRS), and salvage RT for progressing BM initially treated with CT alone (10 patients, 6 SRS). Median follow-up among survivors was 87 months. OS and IP estimates at 4 years were 39% (95% CI = 29-54%) and 44% (95% CI = 31-56%), respectively. OS and IP were not significantly associated with WBRT versus SRS, nor with the pattern of RT use in conjunction with CT. After SRS alone, OS, IP, LP, and RN estimates at 4 years were 47% (95% CI = 31-72%), 50% (95% CI = 29-67%), 8% (95% CI = 3-18%), and 12% (95% CI = 4-24%), respectively. Patients who received SRS to a solitary BM (14 patients, 52%) had significantly better OS (HR = 0.21, 95% CI = 0.06-0.69, P = 0.01) and IP (HR = 0.27, 95% CI = 0.09-0.83, P = 0.02), compared with those who received SRS to ≥ 2 BM. Number of BM was not associated with outcomes after WBRT. This analysis includes the largest reported series of GCT BM treated with SRS. Although WBRT has historically been the standard approach to GCT BM, a subset of patients treated with SRS alone can achieve long-term survival and intracranial disease control. SRS provides excellent local tumor control without excessive rates of RN. Caution is advised when considering SRS in patients with multiple BM, given elevated risk of IP and death. [ABSTRACT FROM AUTHOR]

Ablative radiation therapy (A-RT) defined as a prescribed dose of ~100 Gy BED 10 can achieve durable freedom from local failure (FFLF) and may improve overall survival (OS) versus non-ablative RT for locally advanced pancreas cancer (LAPC). The optimal technique for delivering A-RT is uncertain. We retrospectively compared A-RT outcomes among LAPC patients treated at 2 U.S. institutions with different A-RT techniques excluding those who had surgery at any time. Institution (Inst) A used stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) with automatic beam gating on a 0.35T MR-Linac prescribing 5 fx (50 Gy, 95.6%; 45 Gy 4.4%). Inst B used a hypofractionated ablative RT (HART) delivered on a CBCT-guided Linac with respiratory gating and selective offline replanning, prescribing 25 fx (75 Gy, 80.8%) or 15 fx (67.5 Gy, 19.2%). Elective coverage including the celiac trunk and SMA was routine at both Inst A and B. Clinical characteristics were compared using Chi square or Fisher's exact test. FFLF as per RECIST, freedom from distant failure (FFDF), and overall survival (OS) were estimated from RT with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression model was used for univariate (UVA) and multivariate (MVA) analysis. 211 patients (n = 91, SMART; n = 120, HART) were evaluated. Similar baseline characteristics (SMART vs. HART) included maximum tumor size (3.7 vs. 3.8 cm), median pre-RT CA19-9 level (55 vs. 70 U/mL), induction FOLFIRINOX or gemcitabine/nab-paclitaxel use (82.4% vs. 85.8%), and median induction chemo duration (3.9 vs. 3.7 months). Significant differences (SMART vs. HART) included median age (71 vs. 68 years; P = 0.004), ECOG performance status 0 (41.8% vs. 90.0%; p<.001), head tumor (80.2 vs. 62.5%; P = 0.005), and N+ (25.3% vs. 42.5%; p<.001). SMART plans were hotter (e.g., GTV V120% 14.5 vs. 0.0 cc; p<.001) with higher target coverage (e.g., median GTV D90 scaled 101.1% vs. 84.5%; p<.001). Median follow-up from A-RT was 12.0 vs. 17.5 months (p<.001). 2-yr FFLF, FFDF, and OS for SMART vs. HART were 85.6% vs. 69.0% (p<.001), 30.3% vs. 26.5% (P = 0.513), and 31.0% vs. 35.3% (P = 0.056). On MVA, worse FFLF was associated with 15-25 vs. 5 fractions (HR 4.982, 95% CI = 1.105-22.454) and induction non-FOLFIRINOX vs. FOLFIRINOX (HR 2.010 (95% CI = 1.023-3.949) while worse OS was associated with higher GTV V120% (HR 1.016, 95% CI = 1.001-1.031). Acute grade >3 toxicity was similar (3.3% vs. 5.8%; P = 0.390) while less late grade >3 toxicity occurred after SMART (2.2% vs. 9.2%; P = 0.037). Favorable 2-yr FFLF and OS were achieved after induction chemo and A-RT for LAPC regardless of delivery technique. Higher FFLF after SMART may be related to higher GTV coverage, albeit this was not significant on MVA. Despite this, OS was similar potentially due to more unfavorable baseline characteristics among the SMART cohort. Lower rates of late grade >3 toxicity may have been facilitated by online adaptive RT. [ABSTRACT FROM AUTHOR]

Purpose: Patterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy are not well described., Methods and Materials: We identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure [LRF], distant failure, progression-free survival, colostomy-free survival, and overall survival [OS]), patterns of failure, and salvage therapies were collected. Failures were analyzed using competing risk methods, whereas survival endpoints were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months of completing IMRT., Results: A total of 375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for the American Joint Committee on Cancer stages 0 to I, II, and III, respectively. Six-year rates of LRF, distant failure, progression-free survival, colostomy-free survival, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse 6-year OS than patients without LRF (44% vs 86%, P < .0001). Approximately 30% of patients who underwent salvage therapy were alive to 10 years after recurrence, compared with none of the patients who were managed with chemotherapy alone or the best supportive care., Conclusions: This large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS)., Objective: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort., Design, Setting, and Participants: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021., Intervention: SRS for RCC BMs., Outcome Measurements and Statistical Analysis: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death., Results and Limitations: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041)., Conclusions: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting., Patient Summary: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed., Methods: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk., Results: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%., Conclusion: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine., Case Presentation: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution., Conclusions: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization., (© 2024. The Author(s).)

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods : We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results : Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions : Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.

Background: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data., Methods: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression., Results: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted β for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted β for systemic therapy = +$270; 95% CI, $176-$365)., Conclusions: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Purpose: Intravascular tumor emboli in axillary soft tissue (ITE) is a rare pathologic finding in breast cancer and is associated with higher axillary nodal disease burden. The independent prognostic and predictive value of this entity is unknown, as is the role of radiation therapy for ITE., Methods and Materials: We analyzed a prospectively maintained database of breast cancer patients treated from 1992 to 2020. Patients with ITE were matched to those without (1:2) based on propensity scores to control for potential confounding factors. Locoregional (LRR) and distant recurrence (DR) were evaluated using competing risks methods accounting for death as a competing event. Overall survival (OS) and disease-free survival (DFS) were evaluated by Cox regression models. Among patients with ITE, we also evaluated whether RT improved outcomes., Results: Among 2377 total patients, 129 had ITE, of whom 126 were propensity score matched to 252 without ITE. Median follow-up from time of surgery was 5.5 years (IQR 2.3, 9.7). There were no statistically significant differences in the 5-year incidence of LRR between groups (5.4% [95% CI, 1.6%-13%] with ITE vs 10% [95% CI, 6.7%-15%] without, P = .53) or DR (24% [95% CI, 15% 35%] with ITE vs 21% [95% CI, 16%-27%] without, P = .51). Five-year OS and DFS did not differ between groups ( P > .9 for both comparisons, patients with ITE vs without ITE). In analyzing the effect of RT among patients with ITE, receipt of RT was associated with significantly improved DFS (HR, 0.34, 95% CI, 0.12-0.93, P = .04)., Conclusions: Patients with ITE do not exhibit significantly worse LRR, DR, DFS, or OS compared with a propensity-score-matched cohort without ITE. However, among patients with ITE, those who received RT demonstrated significantly improved DFS. Larger studies with longer follow-up are needed to evaluate the prognostic and predictive implications of ITE., (© 2024 The Author(s).)

Purpose: Colorectal liver metastases (CLMs) represent a radioresistant histology. We aimed to investigate CLM radiation therapy (RT) outcomes and explore the association with treatment parameters., Methods and Materials: This retrospective analysis of CLM treated with RT at Memorial Sloan Kettering Cancer Center used Kaplan-Meier analysis to estimate freedom from local progression (FFLP), hepatic progression-free, progression-free, and overall survival (OS). Cox proportional hazards regression was used to evaluate association with clinical factors. Dose-response relationship was further evaluated using a mechanistic tumor control probability (TCP) model., Results: Ninety patients with 122 evaluable CLMs treated 2006 to 2019 with a variety of RT fractionation schemes with a median biologically effective dose (α/β = 10; BED10) of 97.9 Gy (range, 43.2-187.5 Gy) were included. Median lesion size was 3.5 cm (0.7-11.8 cm). Eighty-seven patients (97%) received prior systemic therapy, and 73 patients (81%) received prior liver-directed therapy. At a median follow-up of 26.4 months, rates of FFLP and OS were 62% (95% CI, 53%-72%) and 75% (66%-84%) at 1 year and 42% (95% CI, 32%-55%) and 44% (95% CI, 34%-57%) at 2 years, respectively. BED10 below 96 Gy and receipt of ≥3 lines of chemotherapy were associated with worse FFLP (hazard ratio [HR], 2.69; 95% CI, 1.54-4.68; P < .001 and HR, 2.67; 95% CI, 1.50-4.74; P < .001, respectively) and OS (HR, 2.35; 95% CI, 1.35-4.09; P = .002 and HR, 4.70; 95% CI, 2.37-9.31; P < .001) on univariate analyses, which remained significant or marginally significant on multivariate analyses. A mechanistic Tumor Control Probability (TCP) model showed a higher 2-Gy equivalent dose needed for local control in patients who had been exposed to ≥ 3 lines of chemotherapy versus 0 to 2 (250 ± 29 vs 185 ± 77 Gy for 70% TCP)., Conclusions: In a large single-institution series of heavily pretreated patients with CLM undergoing liver RT, low BED10 and multiple prior lines of systemic therapy were associated with lower local control and OS. These results support continued dose escalation efforts for patients with CLM., Competing Interests: This was partly funded by the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Paul B. Romesser received research funding (2019) and serves as a consultant for EMD Serono (2018-present), receives research funding from XRAD Therapeutics (2022-present), is a consultant for Faeth Therapeutics (2022-present), is a consultant for Natera (2022-present), and is a volunteer on the advisory board for the HPV Alliance and Anal Cancer Foundation nonprofit organizations. Paul B. Romesser is also supported by an NIH/NCI grant (K08CA255574). Abraham J. Wu receives unrelated grants funded by CivaTech Oncology and participates on the scientific advisory board for Simphotek. Marsha Reyngold has Elekta and Varian research grants and speaker fees from Elekta outside of the submitted work., (© 2023 The Authors.)

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT)., Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed., Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance ( P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention)., Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality., Competing Interests: J. Isabelle Choi reports personal fees from Varian Medical Systems outside of the scope of this work., (© 2023 The Author(s).)

We describe a dataset from patients who received ablative radiation therapy for locally advanced pancreatic cancer (LAPC), consisting of computed tomography (CT) and cone-beam CT (CBCT) images with physician-drawn organ-at-risk (OAR) contours. The image datasets (one CT for treatment planning and two CBCT scans at the time of treatment per patient) were collected from 40 patients. All scans were acquired with the patient in the treatment position and in a deep inspiration breath-hold state. Six radiation oncologists delineated the gastrointestinal OARs consisting of small bowel, stomach and duodenum, such that the same physician delineated all image sets belonging to the same patient. Two trained medical physicists further edited the contours to ensure adherence to delineation guidelines. The image and contour files are available in DICOM format and are publicly available from The Cancer Imaging Archive ( https://doi.org/10.7937/TCIA.ESHQ-4D90 , Version 2). The dataset can serve as a criterion standard for evaluating the accuracy and reliability of deformable image registration and auto-segmentation algorithms, as well as a training set for deep-learning-based methods., (© 2022. The Author(s).)

Introduction: Radiation therapy (RT) for anorectal cancer after prior prostate cancer RT is usually avoided due to concern for complications. Data on this topic is scarce. Our aim was to evaluate tolerability, toxicity, and clinical outcomes associated with a second course of pelvic radiation in men with de novo anorectal cancers previously treated with RT for prostate cancer., Materials/methods: We conducted a single-institution retrospective study of men treated with RT for rectal or anal cancer after prior prostate RT. Toxicity data were collected. Treatment plans were extracted to assess doses to organs at risk and target coverage. Cumulative incidence was calculated for local and distant progression. Kaplan-Meier curves were used to estimate overall survival (OS) and progression-free survival (PFS)., Results: We identified 26 patients who received anorectal RT after prostate cancer RT: 17 for rectal cancer and 9 for anal cancer. None had metastatic disease. Prior prostate RT was delivered using low dose rate brachytherapy (LDR), external beam RT (EBRT), or EBRT + LDR. RT for rectal cancer was delivered most commonly using 50.4Gy/28 fractions (fr) or 1.5 Gy twice-daily to 30-45 Gy. The most used RT dose for anal cancer was 50Gy/25 fr. Median interval between prostate and anorectal RT was 12.3 years (range:0.5 - 25.3). 65% and 89% of rectal and anal cancer patients received concurrent chemotherapy, respectively. There were no reported ≥Grade 4 acute toxicities. Two patients developed fistulae; one was urinary-cutaneous after prostate LDR and 45Gy/25fr for rectal cancer, and the other was recto-vesicular after prostate LDR and 50Gy/25fr for anal cancer. In 11 patients with available dosimetry, coverage for anorectal cancers was adequate. With a median follow up of 84.4 months, 5-yr local progression and OS were 30% and 31% for rectal cancer, and 35% and 49% for anal cancer patients, respectively., Conclusion: RT for anorectal cancer after prior prostate cancer RT is feasible but should be delivered with caution since it poses a risk of fistulae and possibly bleeding, especially in patients treated with prior LDR brachytherapy. Further studies, perhaps using proton therapy and/or rectal hydrogel spacers, are needed to further decrease toxicity and improve outcomes., Competing Interests: PR reports prior research funding from and is a consultant for EMD Serono. MJZ is a consultant for Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hilal, Wu, Reyngold, Cuaron, Navilio, Romesser, Dreyfuss, Yin, Zhang, Bai, Berry, Zinovoy, Nusrat, Pappou, Zelefsky, Crane and Hajj.)

Purpose: Patient experience scores are increasingly important in measuring quality of care and determining reimbursement from payers, including the Hospital Value-Based Purchasing Program and the Radiation Oncology Model. However, the role of bias in patient experience scores in oncology is unknown, raising the possibility that such payment structures may inadvertently perpetuate bias in reimbursement. Therefore, the authors characterized patient-, physician-, and practice-level predictors of patient experience scores in patients undergoing radiation therapy., Methods: The authors retrospectively reviewed patient experience surveys for radiation oncology patients treated at two large multisite academic cancer centers. The outcome was responses on four survey questions. Covariates included self-reported patient demographics, physician characteristics, practice setting characteristics, and wait-time rating linked to each survey. Multivariable ordinal regression models were fitted to identify predictors of receiving a higher score on each of the survey questions., Results: In total, 2,868 patients completed surveys and were included in the analysis. Patient experience scores were generally high, with >90% of respondents answering 5 of 5 on the four survey items. Physician gender was not associated with any measured patient experience outcomes (P > 0.40 for all). Independent predictors of higher score included a wait-time experience classified as "good" compared with "not good" (q < .001 for all)., Conclusions: Oncology practices aiming to improve patient experience scores may wish to focus their attention on improving wait times for patients. Although a difference in patient experience scores on the basis of physician gender was not observed, such bias is likely to be complex, and further research is needed to characterize its effects., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Pelvic radiation therapy (RT) is standard of care for patients with locally advanced rectal cancer (LARC). Premature ovarian insufficiency (POI) in premenopausal women is a possible side effect. The purpose of our study was to evaluate factors associated with POI in women younger than 50 years, treated with pelvic RT for LARC, including those who underwent ovarian transposition (OT)., Methods and Materials: We retrospectively reviewed the records of women younger than 50 years treated with pelvic RT for LARC at our institution between 2001 and 2019. Clinical and hormonal data were used to determine ovarian function. The ovaries and uterus were contoured and dose volume histograms were generated. Association of clinical and dosimetric factors with POI within 12 months of RT was evaluated using Wilcoxon-rank sum test and Fisher's exact test., Results: We identified 76 premenopausal women at time of RT with median age of 43 years (range, 20-49). Twenty-six women (34%) underwent OT. Neoadjuvant, concurrent, and adjuvant chemotherapy was administered in 56 (74%), 69 (91%), and 26 (34%) women, respectively. Median RT dose was 50 Gy/25 fractions. Among 75 women with 12 months of follow-up, 25% had preservation of ovarian function, all in the OT group. Ovarian function was preserved in 19 (76%) women who underwent OT. The median of ovarian mean dose was 1.7 Gy in the OT group versus 44.8 Gy in the non-OT group ( P < .001). OT and age at RT were significantly associated with POI ( P < .001). No patient with ovarian mean dose less than 1.36 Gy developed POI., Conclusions: OT was significantly associated with reduced risk of POI by enabling lower radiation doses to the ovaries. OT should be considered in young patients undergoing pelvic RT. Although there appears to be a significant association between ovarian mean dose and POI, larger studies are needed to find a dosimetric threshold. Our results suggest keeping the dose to the ovaries as low as reasonably achievable in patients who undergo OT and pelvic RT., (© 2021 The Author(s).)

Background: More than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT., Methods: We retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks., Results: Forty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group., Conclusions: Greater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-116). The authors have no conflicts of interest to declare, (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: Accurate deformable registration between computed tomography (CT) and cone-beam CT (CBCT) images of pancreatic cancer patients treated with high biologically effective radiation doses is essential to assess changes in organ-at-risk (OAR) locations and shapes and to compute delivered dose. This study describes the development and evaluation of a deep-learning (DL) registration model to predict OAR segmentations on the CBCT derived from segmentations on the planning CT., Methods: The DL model is trained with CT-CBCT image pairs of the same patient, on which OAR segmentations of the small bowel, stomach, and duodenum have been manually drawn. A transformation map is obtained, which serves to warp the CT image and segmentations. In addition to a regularity loss and an image similarity loss, an OAR segmentation similarity loss is also used during training, which penalizes the mismatch between warped CT segmentations and manually drawn CBCT segmentations. At test time, CBCT segmentations are not required as they are instead obtained from the warped CT segmentations. In an IRB-approved retrospective study, a dataset consisting of 40 patients, each with one planning CT and two CBCT scans, was used in a fivefold cross-validation to train and evaluate the model, using physician-drawn segmentations as reference. Images were preprocessed to remove gas pockets. Network performance was compared to two intensity-based deformable registration algorithms (large deformation diffeomorphic metric mapping [LDDMM] and multimodality free-form [MMFF]) as baseline. Evaluated metrics were Dice similarity coefficient (DSC), change in OAR volume within a volume of interest (enclosing the low-dose PTV plus 1 cm margin) from planning CT to CBCT, and maximum dose to 5 cm 3 of the OAR [D(5cc)]., Results: Processing time for one CT-CBCT registration with the DL model at test time was less than 5 seconds on a GPU-based system, compared to an average of 30 minutes for LDDMM optimization. For both small bowel and stomach/duodenum, the DL model yielded larger median DSC and smaller interquartile variation than either MMFF (paired t-test P < 10 -4 for both type of OARs) or LDDMM (P < 10 -3 and P = 0.03 respectively). Root-mean-square deviation (RMSD) of DL-predicted change in small bowel volume relative to reference was 22% less than for MMFF (P = 0.007). RMSD of DL-predicted stomach/duodenum volume change was 28% less than for LDDMM (P = 0.0001). RMSD of DL-predicted D(5cc) in small bowel was 39% less than for MMFF (P = 0.001); in stomach/duodenum, RMSD of DL-predicted D(5cc) was 18% less than for LDDMM (P < 10 -3 )., Conclusions: The proposed deep network CT-to-CBCT deformable registration model shows improved segmentation accuracy compared to intensity-based algorithms and achieves an order-of-magnitude reduction in processing time., (© 2021 American Association of Physicists in Medicine.)

Importance: Surgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease., Objective: To determine the association of hypofractionated ablative radiation therapy (A-RT) with survival for patients with locally advanced pancreatic cancer (LAPC) treated with a novel radiation planning and delivery technique., Design, Setting, and Participants: This cohort study included 119 consecutive patients treated with A-RT between June 2016 and February 2019 and enrolled in a prospectively maintained database. Patients were treated with a standardized technique within a large academic cancer center regional network. All patients with localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5 cm luminal abutment with the primary tumor were eligible., Interventions: Ablative RT (98 Gy biologically effective dose) was delivered using standard equipment. Respiratory gating, soft tissue image guidance, and selective adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs., Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary outcomes included incidence of local progression and progression-free survival., Results: Between 2016 and 2019, 119 patients (59 men, median age 67 years) received A-RT, including 99 with T3/T4 and 53 with node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. Most (116 [97.5%]) received induction chemotherapy for a median of 4 months (0.5-18.4). Median OS from diagnosis and A-RT were 26.8 and 18.4 months, respectively. Respective 12- and 24-month OS from A-RT were 74% (95% CI, 66%-83%) and 38% (95% CI, 27%-52%). Twelve- and 24-month cumulative incidence of locoregional failure were 17.6% (95% CI, 10.4%-24.9%) and 32.8% (95% CI, 21.6%-44.1%), respectively. Postinduction CA19-9 decline was associated with improved locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%) with no grade 4 to 5 events., Conclusions and Relevance: This cohort study of patients with inoperable LAPC found that A-RT following multiagent induction therapy for LAPC was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with LAPC are warranted.

Purpose: Multibeam intensity modulated radiation therapy (IMRT) enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP)., Methods and Materials: Between July 2010 and January 2013, patients with node-positive breast cancer received inverse-planned, multibeam IMRT to the breast or chest wall and regional nodes, including the internal mammary nodes (IMNs). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of RP grade 3 or greater and changes in pulmonary function measured with the Common Terminology Criteria for Adverse Events version 3.0 scales, pulmonary function tests and community-acquired pneumonia questionnaires, obtained at baseline and 6 months after IMRT. Clinical follow-up was every 6 months for up to 5 years., Results: Median follow-up was 53.4 months (range, 0-82 months). Of 113 patients enrolled, 104 completed follow-up procedures. Coverage of the breast or chest wall and IMN was comprehensive (median 48.1 Gy and 48.9 Gy, respectively). The median volume of lung receiving a high dose (V20Gy) and a low dose (V5) was 29% and 100%, respectively. The overall rate of respiratory toxicities was 10.6% (11/104), including 1 grade 3 RP event (0.96%). No differences were found in pulmonary function test or community-acquired pneumonia scores after IMRT. The 5-year rates of locoregional recurrence-free, disease-free, and overall survival were 93.2%, 63.6%, and 80.3%, respectively., Conclusions: Multibeam IMRT in patients with breast cancer receiving regional nodal irradiation was dosimetrically feasible, based on early treatment planning criteria. Despite the large volume of lung receiving low-dose RT, the incidence of grade 3 RP was remarkably low, justifying inverse-planned IMRT as a treatment modality for patients with high-risk breast cancer in whom conventional RT techniques prove inadequate., (Copyright © 2018 Elsevier Inc. All rights reserved.)