Radiotherapy (RT) +/- androgen deprivation therapy (ADT) plays a key role in salvage therapy of prostate cancer (PC) recurrent after radical prostatectomy. However, not all patients benefit, and there is an unmet need for biomarkers to distinguish responders from non-responders (defined as those with second biochemical failure after salvage). We hypothesized that somatic mutations in primary PC are correlated with response to salvage RT+ADT. We retrospectively identified 718 consecutive PC patients treated with post-operative RT at a single institution from 1992-2013, of whom 40 were treated with salvage RT+ADT and had formalin-fixed, paraffin-embedded prostatectomy and matched normal tissues available for DNA extraction. The indication for salvage therapy was biochemical failure after an undetectable post-operative PSA in 72%, gross local recurrence in 17%, and persistently elevated PSA after surgery in 11%. Median RT dose was 64.8 Gy, and all patients received concurrent ADT. Whole exome sequencing (WES) was performed to an average depth of 162X (r, 70.7-219). We tested for association between somatic mutations and clinical outcomes using the log-rank test and Cox proportional hazards model. Median age at salvage was 64.5 yrs. High-quality WES data were available in 39 patients. With a median follow-up of 122 months (range, 29-248), 21 experienced second biochemical failure after salvage, while 18 did not. Median time to second biochemical failure was 82.3 months (range, 1.2-140). Overall tumor mutational burden (TMB) was 2.72 mutations/Mb (range, 1.4-12.8). TMB among those with second biochemical failure was 3.9 vs. 3.1 among those without (p=0.29). The most common mutations detected in the overall cohort were PLEC and TTN (n=7). The presence of mutations in BRCA2 (n = 1, p < 0.01, HR = 37 (95% CI: 2.3-600)), CASZ1 (n = 3, p < 0.01, HR = 10 (95% CI: 2.4-44)), XRCC4 (n = 1, p = 0.017, HR = 9.0 (95% CI: 1.0-8.)), ATR (n = 2, p < 0.01, HR = 7.8 (95% CI: 1.6-39)), WDR26 (n = 3, p < 0.01, HR = 6.5 (95% CI: 1.7-24)) and MYT1 (n = 3, p < 0.01, HR = 6.4 (95% CI: 1.5-20)) was significantly correlated with second biochemical failure after salvage RT+ADT. In contrast, none of the patients with mutations in FOXA1 (n=4, p = 0.046, HR: not calculable) experienced second biochemical failure during follow-up. In this cohort of PC patients with >10 years median follow-up after post-prostatectomy salvage RT+ADT, WES revealed that mutations in BRCA2, CASZ1, XRCC4, and ATR were associated with second biochemical failure after salvage therapy, while FOXA1 mutation was associated with favorable outcomes. These findings require validation in larger cohorts, but suggest that somatic mutations may serve as biomarkers to identify patients at greatest risk for recurrence after post-prostatectomy salvage therapy. Keisuke Otani, David J. Konieczkowski, Yukako Otani, Grace Cerrato, Shulin Wu, Philip J. Saylor, Douglas M. Dahl, Chin-Lee Wu, Sophia C. Kamran, Jason A. Efstathiou, David T. Miyamoto. Somatic mutations and outcomes of salvage radiation and hormonal therapy for prostate cancer recurrence after prostatectomy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A053.

BACKGROUND/OBJECTIVES:Treatment delays have been shown to be associated with overall survival (OS) in head and neck squamous cell carcinomas (HNSCCs). Given the slow tumor growth kinetics of adenoid cystic carcinoma (ACC), it is unclear if delays have a similar impact in this tumor histology. METHODS:We queried the National Cancer Database for patients diagnosed with non-metastatic ACC between the years 2004 and 2019 and treated with surgery followed by RT. A multivariable Cox regression model was used to examine the associations between the time from diagnosis to surgery, the duration of RT, and OS. RESULTS:A total of 1449 patients were included for analysis. Increased time from diagnosis to surgery (HR: 1.02, 95% CI: 1.01-1.03, p < 0.001) and duration of RT (HR: 1.14, 95% CI: 1.04-1.25, p = 0.004) were associated with worse survival on UVA, while time from surgery to RT start was not (p = 0.647). Increased duration of RT (aHR: 1.13, 95% CI: 1.03-1.24, p = 0.012) remained significantly associated with OS on multivariable analysis, while time from diagnosis to surgery (aHR: 1.00, 95% CI: 0.98-1.02, p = 0.979) did not. CONCLUSIONS:Delays in treatment initiation and in the interval from surgery to radiation did not result in clinically significant differences in survival in this analysis, while prolonged duration of radiation therapy was significantly associated with worse survival. These findings are hypothesis-generating and suggest that treatment delays for ACC may have different effects on oncologic outcomes than those for HNSCC; however, prospective data is paramount to verify these results before strong conclusions can be made.

BACKGROUND:Volumetric Modulated Arc Therapy (VMAT) is integral to head and neck (HN) radiation therapy; however, plan robustness may be compromised at air-tissue interfaces. Highly modulated fluence directed at these areas can produce significant unexpected high-dose regions in the event of minor variations in tissue density. PURPOSE:This study characterizes an instability in VMAT planning for HN radiation therapy (RT) occurring at the interface between target volume (e.g. mucosal primary tumor) and internal air spaces (e.g. pharyngeal lumen, sinuses, nasal cavity, etc.). A density-override based planning technique is presented and validated to mitigate this instability. METHODS:Treatment plans for fifteen HN patients receiving VMAT RT at our institution between 2023 and 2024 were retrospectively analyzed. All patients received 60-69.96 Gy in 30-33 daily fractions using 6 MV photons. To model swelling or tumor growth near the air-tumor interface, verification plans were generated by overriding internal air within 3 mm of the planning target volume (PTV) to soft tissue density (HU = 0). A robustness-enhancing technique was evaluated, wherein optimization was performed with luminal air overridden to HU = -300, followed by recalculation and renormalization using the original CT HU values. Robustness was then reassessed after overriding luminal air to HU = 0. RESULTS:Baseline plans demonstrated controlled hotspot magnitudes within the BODY, with a median D0.1cc of 109.0% [Interquartile range: 107.8-110.4]. Simulated tissue-air interface changes produced substantially elevated hotspots in verification plans, increasing to a median D0.1cc of 115.6% [111.9-126.9], corresponding to a median paired increase of 9.0% (Wilcoxon p = 1.22 × 10- 4). Robust plans generated using the proposed density-override optimization maintained comparable baseline dosimetry (median D0.1cc 108.1% [107.4-108.7]) while demonstrating stable hotspot behavior under simulated density perturbations (median D0.1cc 108.1% [107.1-108.6], p = 0.18). Target coverage remained preserved, with robust verification plan D95 values ranging from 99.7% to 100.5% (p = 0.26). CONCLUSION:A density-override optimization approach mitigates hotspot formation at air-tumor interfaces, producing VMAT plans that remain dosimetrically stable despite variation at internal air-tumor interfaces.

BACKGROUND/OBJECTIVES:Stereotactic body radiation therapy (SBRT) provides improved pain response and local control for spinal metastases. However, management of local failure after initial SBRT is challenging. We report institutional outcomes, dosimetry, and toxicity for reSBRT following SBRT. METHODS:We retrospectively reviewed 61 lesions (55 patients) treated with reSBRT after prior SBRT. Both SBRT courses delivered a median dose of 27 Gy. Patients underwent clinical and radiological evaluation every three months. Toxicity was graded using CTCAE v5.0. Dosimetric parameters for the spinal cord (SC), cauda equina (CE), planning organ-at-risk volumes (PRV), and thecal sac were converted to equivalent dose in 2 Gy fractions (EQD2) using the linear-quadratic model (α/β = 2). RESULTS:Median follow-up was 10.3 months. Forty lesions (65%) were cervicothoracic and 21 (35%) were lumbosacral. One- and two-year overall survival (OS) were 45% and 29%, respectively, and one- and two-year local control (LC) were 89% and 88%, respectively. Gastrointestinal primary tumors were associated with inferior LC (HR 2.41, 95% CI 1.11-5.23, p = 0.026). Fifteen patients (27%) reported myelitis/neuropathic symptoms during follow-up; four (7%) developed new post-radiation myelitis or neuropathy (RMN) without radiologic progression. Five patients (9%) developed vertebral compression fractures (VCF). Cumulative EQD2 was not significantly associated with RMN (p = 0.344); all affected patients had thecal sac EQD2 > 95.5 Gy and relevant nerve roots EQD2 > 108 Gy. CONCLUSIONS:ReSBRT provided a favorable LC with acceptable toxicity. High cumulative dose to the thecal sac and nerve roots may contribute to neurologic toxicity as peripheral nerve injury.

Purpose/Objective(s) Radiotherapy (RT) +/- androgen deprivation therapy (ADT) plays a key role in salvage therapy of prostate cancer (PC) recurrent after radical prostatectomy. However, not all patients benefit, and there is an unmet need for biomarkers to distinguish responders from non-responders (defined as those with second biochemical failure after salvage). We hypothesized that somatic mutations in primary PC are correlated with response to salvage RT+ADT. Materials/Methods We retrospectively identified 718 consecutive PC patients treated with post-operative RT at a single institution from 1992-2013, of whom 40 were treated with salvage RT+ADT and had formalin-fixed, paraffin-embedded prostatectomy and matched normal tissues available for DNA extraction. The indication for salvage therapy was biochemical failure after an undetectable post-operative PSA in 72%, gross local recurrence in 17%, and persistently elevated PSA after surgery in 11%. Median RT dose was 64.8 Gy, and all patients received concurrent ADT. Whole exome sequencing (WES) was performed to an average depth of 162X (r, 70.7-219). We tested for association between somatic mutations and clinical outcomes using the log-rank test and Cox proportional hazards model. Results Median age at salvage was 64.5 yrs. High quality WES data was available in 31 patients. With a median follow-up of 122 months (range = 29-248), 16 experienced second biochemical failure after salvage while 15 did not. Median time to second biochemical failure was 82.3 months (range = 1.2-140). Overall tumor mutational burden (TMB) was 3.3 mutations/Mb (range = 1.4-12.9). TMB among those with second biochemical failure was 3.8 vs. 2.8 among those without (p = 0.22). The most common mutations detected in the overall cohort were ALEC (n = 6) and CUX1 (n = 5). The presence of mutations in BRCA2, CASZ1, SYNE1, and AFDN was significantly correlated with second biochemical failure after salvage RT+ADT (see Table 1). Local failure after salvage occurred in 3 patients and was correlated with AFDN mutation (p = 0.0002). In contrast, none of the patients with mutations in WIZ (n = 4) or FOXA1 (n = 3), experienced second biochemical failure during follow-up. Conclusion Using WES analysis, we found that mutations in BRCA2, CASZ1, SYNE1, and AFDN correlated with second biochemical failure after salvage therapy with RT+ADT. These findings require validation in larger cohorts, but suggest that somatic mutations could potentially serve as predictive biomarkers for post-prostatectomy salvage therapy.

Importance Nasopharyngeal carcinoma (NPC) presents unique challenges in nonendemic regions, with varying patient characteristics and outcomes compared with endemic populations. Objective To fill gaps in the current understanding of NPC by focusing on a US population, comparing patient characteristics and treatment outcomes with endemic populations, and identifying key factors to inform management and follow-up protocols in Western health care settings. Design, Setting, and Participants This retrospective cohort study included patients with NPC treated at a single large US tertiary academic medical center from 2000 to 2023. The study analyzed patient demographics, tumor characteristics, treatment modalities, and survival outcomes. Data were analyzed from January to July 2024. Main Outcomes and Measures Overall survival (OS), progression-free survival (PFS), and recurrence-free survival, stratified by patient characteristics, tumor types, Epstein-Barr virus (EBV) status, and p16 expression. Results The sample included 159 adult patients with NPC (median [range] age, 53.5 [18-90] years; 117 [73.6%] male), with 23 African American patients (15.3%), 21 Asian patients (14.0%), and 106 White patients (70.7%). World Health Organization type III tumors predominated (88 patients [68.8%]), followed by type II (25 patients [19.5%]) and type I (15 patients [11.7%]). EBV positivity rates varied significantly by race (Asian: 13 patients [81.3%]; African American: 17 patients [63.0%]; White: 40 patients [47.0%]; P = .03) and WHO type (type III: 50 patients [72.5%]; type II: 10 patients [48.0%]; type I: 0 patients; P < .001). p16 status, a proxy for human papillomavirus status, did not vary by race but did vary by histopathologies (type III: 12 patients [28.5%]; type II: 12 patients [63.0%]; type I: 3 patients [43.0%]; P = .04). On Kaplan-Meier curves, stratifying p16 by EBV status eliminated its assumed association with OS. Multivariate analysis revealed that increasing age (hazard ratio [HR] per 1-year increase, 1.03 [95% CI, 1.00-1.05]; P = .04) and former smoking status (HR, 2.29 [95% CI, 1.03-5.10]; P = .04) were associated with inferior OS, while WHO type III tumors were associated with better OS compared with type I (HR, 0.38 [95% CI, 0.17-0.87]; P = .02). Male sex was associated with worse PFS (HR, 5.35 [95% CI, 1.23-23.30]; P = .03). For recurrence-free survival, former smokers (HR, 25.24 [95% CI, 2.56-249.23]; P = .006), current smokers (HR, 44.97 [95% CI, 2.27-892.10]; P = .01), and patients with advanced stages (IVa/b) (HR, 261.34 [95% CI, 3.96-17 258.06]; P = .009) had significantly increased risk. Conclusions and Relevance This cohort study contributes to the evolving body of knowledge on NPC in nonendemic regions, finding a shift toward WHO type III tumors and underscoring the association of EBV status with survival outcomes, while highlighting the lack of association between human papillomavirus status and outcomes. Smoking history, advanced stage at diagnosis, male sex, and increasing age emerged as adverse factors. Notably, WHO type I tumors demonstrated particularly poor outcomes, highlighting the need for more intensive follow-up in this subgroup.

PURPOSE:To report the first cohort of children with spinal and sacrococcygeal chordomas (CH) and chondrosarcomas (CHS) treated with proton-based radiation therapy (PRT). MATERIALS AND METHODS:Between 1989 and 2019, 52 pediatric patients ≤22 years old with spinal CH (n = 43) or CHS (n = 9) were treated with PRT at a single institution. The primary tumor originated in the C-spine (n = 37, 71%), T-spine (n = 6, 12%), L-spine (n = 7, 14%), or sacrum (n = 2, 3%). The CH group included 33 conventional and 10 atypical/poorly differentiated CH. The CHS group included 5 conventional and 4 mesenchymal CHS. Pre-RT chemotherapy was administered to 13 (25%) patients. Salvage radiation was delivered to 13 (25%) patients with progressive disease. The median total dose was 74.5 Gy (RBE) [IQR, 69.8-76 Gy (RBE)], delivered in 1.8 to 2.5 Gy (RBE) daily fractions. Primary endpoints were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). A univariate and multivariable Cox regression analysis was performed to identify prognostic and predictive factors. RESULTS:At a median follow-up of 11.4 years (IQR, 5.7-19.8) from the date of diagnosis, 17 (32.7%) patients recurred (8 local, 7 distant, and 2 iatrogenic). Fifteen of these patients died of disease. The 5-, 10-, and 20-year OS were 82.7%, 72.3% and 72.3%, respectively. The 5-, 10-, and 20-year DSS were 86.1%, 77.5%, and 77.5%, respectively. The 5-, 10-, and 20-year PFS were 72.3%, 70.1% and 70.1%, respectively. The 20-year OS, DSS, and PFS for conventional CH were 93.9%, 97%, and 87.9%, respectively. Factors significantly associated with worse outcomes were poorly differentiated CH subtype, pre-RT chemo, and low KPS (P < .05). Pre-RT tumor progression was found to be a significant prognostic factor for PFS (P = .02). Two patients developed late grade 3 toxicities. CONCLUSIONS:This is the largest study of pediatric spinal and sacrococcygeal CH/CHS to date. High-dose PRT following surgical resection offers high disease control rates for conventional CH/CHS.

Background:Though promising retrospective and prospective studies have reported on stereotactic ablative radiation therapy(SABR) for management of lung metastases from sarcoma primaries, they are limited by small patient numbers. Methods:The primary outcomes of interest were 1-year and 2-year local control (LC) and Grade 3-5 toxicities. Secondary outcomes were 1-year overall survival (OS) and 2-year OS. Weighted random effects meta-analyses using the DerSimonian and Laird methods were performed to calculate effect sizes. Results:Thirteen studies were identified with 533 patients and 940 lung metastases. The median prescription dose was 50 Gy (range: 48-60 Gy) in 5 fractions (range: 4-10). Following SABR, 1- and 2-year pooled LC rates were 97% (95% CI: 95-98%) and 91% (95% CI: 88-95%), respectively. Pooled 1- and 2-year OS rates were 85% (95% CI: 80-90%) and 68% (95% CI: 57-80%), respectively. The estimated incidence of Grade 3-5 toxicities following SABR was 0.1% (95% CI: 0-0.5%). Conclusion:SABR for sarcoma pulmonary metastases resulted in excellent LC with minimal toxicities.

Prostate cancer is driven by androgen receptor (AR) signaling, and radiotherapy (RT) with or without androgen deprivation therapy (ADT) offers a second opportunity at cure for men with local or biochemical recurrence after prostatectomy. In the metastatic setting, AR RNA splice variants (ARVs), including ligand-independent AR-V7, modulate ADT response and tumor radiosensitivity. Here, we hypothesized that ARVs in primary prostate cancer may likewise modulate response to subsequent salvage RT+ADT. We performed ultra-deep RNA-seq of the AR transcript pool from prostatectomy specimens from 43 men who later received salvage RT+ADT. Eighty-six percent of patients had detectable ARVs (median 3, range 0-12). Of the thirty-two unique ARVs detected, only AR-V7 (present in 14% of patients) was associated with outcomes after salvage RT+ADT (HR for second biochemical failure, 6.2, 95% CI 2.3-16.5, p=0.0003). These results suggest for the first time that AR-V7 may modulate outcomes for localized in addition to metastatic prostate cancer.

BACKGROUND:Pediatric osteosarcoma is an aggressive bone malignancy that presents significant challenges due to high rates of metastatic disease and relapse. It is often treated with palliative radiotherapy for symptom control, but achieving definitive local control (LC) with radiotherapy alone is challenging given its radioresistance. LC may be potentially improved by utilizing stereotactic body radiation therapy (SBRT) to deliver high biologically equivalent doses (BED). METHODS:This study evaluated the LC outcomes of pediatric patients with osteosarcoma and unresectable metastatic disease who were treated with SBRT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed as secondary endpoints. RESULTS:The study included seven patients who received 34 courses of SBRT. The median age at diagnosis was 13.1 and 17.1 years at first SBRT. The common sites for SBRT were extraspinal osseous metastases (56%), pulmonary/mediastinal (29%), and spine (9%). At a median follow-up of 6 months on a per-lesion analysis, LC was achieved in 88% of lesions, with four lesions failing locally. All four local failures were found in patients receiving a BED ≤48 Gy. The median distant PFS was 2.4 months. Toxicities were present in four patients, all of which resolved with supportive treatment. CONCLUSIONS:Our study demonstrated that SBRT is safe and effective at achieving LC in pediatric patients with unresectable metastatic osteosarcoma, though distant progression can limit survival outcomes. Further studies evaluating SBRT in combination with other therapies are needed to address distant progression.

BACKGROUND AND PURPOSE:Reirradiation for recurrent or second primary head and neck cancer (HNC) can result in radiation-induced brachial plexopathy (RIBP), a debilitating side effect. This study aims to identify factors associated with the development of RIBP in patients undergoing reirradiation for recurrent or second primary HNC. MATERIALS AND METHODS:This retrospective cohort study included 48 patients treated from 2015 to 2022 at a single National Cancer Institute-Designated Comprehensive Cancer Center, with a median follow-up duration of 22.7 months post-reirradiation. Patients underwent conventionally fractionated reirradiation, and a total of 72 brachial plexi that received overlapping courses of radiation were analyzed. Primary outcomes measured were the incidence of RIBP and factors contributing to increased risk, including EQD2 (equivalent dose in 2 Gy fractions) maximum point dose (Dmax, defined as 0.03 cc) and volumetric brachial plexus (BP) dosimetric endpoints (V80-V120), comorbidities, time between radiation courses, receipt of systemic therapy, and neck dissection. BP EQD2 was calculated using an alpha/beta of 3 Gy. RESULTS:The crude incidence of RIBP was 23 %, occurring at a median of 9.5 months after reirradiation, with 12- and 24-month rates of 11 % and 16 %, respectively. On univariate analysis, concurrent cisplatin during the second course of radiation (hazard ratio [HR] 9.04, 95 % confidence interval [CI]: 2.70-30.40, p < 0.001) and cumulative EQD2 BP Dmax ≥ 103 Gy2 (HR 1.10, CI: 1.04-1.17, p < 0.001) were significantly associated with RIBP. These factors remained significant on multivariable analysis. RIBP incidence was significantly associated with all cumulative volumetric BP endpoints from V80-V120, with higher RIBP rates for V80 ≥ 1.94 cc, V100 ≥ 1.35 cc, V120 ≥ 0.89 cc, and EQD2 Dmax ≥ 103 Gy2. CONCLUSIONS:This study, the largest to date investigating rates of RIBP in patients with HNC treated with conventionally fractionated reirradiation, found that cumulative EQD2 maximum dose, and the use of concurrent cisplatin during the second RT course, were associated with increased rates of RIBP. Understanding these factors may guide clinicians in the setting of reirradiation, potentially leading to improved patient outcomes.

BACKGROUND:There is a paucity of data on treatment outcomes following stereotactic radiosurgery (SRS) for brain metastases from sarcoma primaries. METHODS:The International Radiosurgery Research Foundation member-sites were queried for patients with brain metastases from sarcoma primaries treated with SRS. Overall survival (OS) and local control (LC) were calculated via Kaplan-Meier analysis. Univariate analyses examined prognostic factors associated with LC and OS via log-rank t-tests and multivariate analyses (MVA) via Cox proportional hazards model. RESULTS:A total of 146 patients with 309 brain metastases were identified. Two-hundred and thirty lesions were treated with single-fraction SRS with a median dose of 20 Gy (15-24 Gy). Ninety-five patients had extracranial metastases, including 75 oligometastatic patients. One- and 2-year OS and LC rates were 47.7% and 37.3%, and 78.3% and 62.2%, respectively. On univariate analyses, superior 1-year OS was noted among leiomyosarcomas (69.7% vs. 42.6%; p = .02) with poorer outcomes among pleomorphic histologies (10.5% vs. 50.7%; p = .002). Pleomorphic histologies were associated with poorer OS on MVA (hazard ratio [HR], 3.13; p = .006). On MVA, LC was inferior among patients of age ≥45 years (HR, 3.78; p < .001) and superior among leiomyosarcomas (HR, 0.31; p = .03). OS was prognosticated based on adverse factors (ie, nonleiomyosarcoma histology and progressive extracranial metastases). Two-year OS for patients with and without adverse features were 78.6% and 31.5%, respectively. CONCLUSIONS:LC outcomes were driven by histology and age with superior LC among leiomyosarcomas and patients of age <45 years. OS was driven by nonleiomyosarcoma histology and the presence of progressive extracranial disease.

Background: Surgery and radiation therapy remain the standard of care for patients with high-grade extremity soft tissue sarcoma that are >5 cm. Radiation therapy is time and labor-intensive for patients, and social determinants of health may affect adherence. The aim of this study was to define demographic, clinical, and treatment factors associated with the completion of radiation therapy and determine if preoperative radiation therapy improved adherence compared to postoperative radiation therapy. Methods: The cohort included patients in the National Cancer Database with high-grade extremity soft tissue sarcoma >5 cm without nodal or distant metastases who received limb-sparing surgery and radiation therapy with microscopically negative R0 margins. Multivariable logistic regression analyses identified factors associated with radiation therapy sequencing and adherence (defined as completion of 50 Gy preoperative radiation therapy or at least 60 Gy postoperative radiation therapy). A multivariable Cox Proportional Hazards model assessed overall survival. Results: Among 2,145 patients, 47.1% received preoperative radiation therapy (n = 1,010), and 52.9% (n = 1135) received postoperative radiation therapy. A greater proportion of patients treated with preoperative (77.2%) versus postoperative radiation therapy (64.9%, P < .0001) received the recommended dose. More patients with private insurance (49.8% vs 35.3% Medicaid vs 44.9% Medicare, P = .011) and patients treated at an academic medical center (52.6% vs 47.4%, P < .001) received preoperative radiation therapy. Patients who received preoperative radiation therapy had lower odds of receiving insufficient doses of radiation therapy (odds ratio 0.34 [95% CI 0.27-0.47]). Neither radiation therapy adherence nor sequencing were independent predictors of overall survival. Conclusions: Patients who received preoperative radiation therapy were more likely to complete therapy and receive an optimal dose than patients treated with postoperative radiation therapy. Preoperative radiation therapy improves adherence and should be widely considered in patients with high-grade extremity soft tissue sarcoma, particularly in patients at risk for not completing therapy. (c) 2023 Elsevier Inc. All rights reserved.

Purpose/Objective(s)Head and neck re-irradiation treatment approach can lead to various side effects like radiation induced brachial plexopathy (RIBP). Factors contributing to brachial plexus injury in the re-irradiation setting need further assessment. We aim to identify these factors to help tailor treatment management.Materials/Methods71 BP sites with 48 patients (pts), treated with re-irradiation between 2015 and 2022 for recurrent head and neck cancer, were assessed. Reverse Kaplan-Meier and logistic regression were used to test the correlation between variables and outcomes. Common terminology criteria of adverse events (CTCAE v5.0) was used to define brachial plexus injury.ResultsThe median age of pts was 65 (range, 29-79), 65% of pts were males, and 88% had ECOG performance status of 0-1. All pts received 1.64-2.12 Gy per fraction with one fraction per day and 5 fractions per week via VMAT. 15% additionally received IORT during salvage treatment ranging from 10-15Gy. 27% of patients in the first course and 88% in the second course of pts had surgery, with RT delivered in the adjuvant setting; the remainder had definitive-intent radiation without surgery. Concurrent chemotherapy was delivered to 67% of pts in the first course (Cisplatin 40%, Cetuximab 17%, Carboplatin +/- Paclitaxel 10%) and 62% in the second course (Carboplatin/Paclitaxel 38%, Cisplatin 16%, Cetuximab 6%, Nivolumab 2%). The median duration between RT courses was 34 months (4.6-216). With a median follow-up of 20.1 months, the cumulative incidence of RIBP at 1- and 2- year for the whole cohort was 9% and 17%, respectively. The cumulative incidence of RIBP was lower in pts with a cumulative Dmax of less than 116Gy, (1-year: 2% vs 22%, p <.001), Dmean of less than 70Gy, (1-year: 4% vs 18%, p .003). When V80 less than 1.9cc, V90 less than 1.5cc and V100 less than 1.3cc, the 1-year cumulative incidence of RIBP was 3% vs 18% p .004, 2% vs 20% p 0.001, and 6% vs 18% p .023, respectively. The 1- year cumulative incidence of RIBP in correlation with concurrent cisplatin was 62% vs 3%, p <.001. 1- year cumulative incidence of RIBP with age less than 65 was 18% vs 2%, p .002. 1-year cumulative incidence of RIBP with positive neck lymph node was 22% vs 3% p <.001. On multivariate analysis, age below 65 (HR 9.7 [CI 1.7-57], p .012), Dmax above 116Gy (HR 23 [CI 2.2-245], p .009) and positive neck lymph node during second radiation (HR 6.1 [CI 1.1-33], p .039] continued to show increasing risk of RIBP.ConclusionRIBP was higher in younger pts, pts received concurrent cisplatin during the 2nd course, positive neck lymph node, cumulative Dmax 116Gy, mean 70Gy, V80 1.9cc, V90 1.5cc and V100 1.3cc. We identified 10 cases with brachial plexopathy. six pts had grade I, 3 pts had grade II and one pt had grade III brachial plexopathy. Median time to develop RIBP was 9.5 months (range, 1-17.1). Prospective study, longer follow up, and higher numbers are warranted.

Purpose/Objective(s)Data is lacking regarding the best treatment option for patients (pts) with RM-HNSCC after progression on ICI. Weekly PCC has reduced toxicity compared with triweekly PCC. We report the outcomes of pts treated with weekly PCC after progression on ICI.Materials/MethodsWe analyzed pts with RM-HNSCC who received weekly PCC (paclitaxel 45 mg/m2, carboplatin area under the curve 1.5, cetuximab 400 mg/m2 first week, and 250 mg/m2 weekly thereafter) after progression on ICI between July 2016 and November 2022. We collected data on tumor site, P-16, combined positive score (CPS), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). PFS was defined as the time from PCC initiation and disease progression or death. OS was defined as the time from PCC initiation and death.ResultsOf the 44 pts available for analysis, 84% were male, and the median age was 60 yrs (IQR: 53, 68). The most common tumor site was oropharynx (48%), followed by oral cavity (27%) and others (25%). Nineteen pts (43%) were initially treated with ICI-chemotherapy and 25 (57%) with ICI alone. The median duration of treatment with ICI was 5.1 months (mo) (IQR: 2.7, 10.6). CPS values were available in 33 pts: 0% (8 pts), 1-20% (10 pts), and 21-100% (15 pts). The median follow-up time for PFS and OS was 4 mo (IQR: 2.8) and 8 mo (IQR: 3, 11), respectively. ORR were as follows: partial, 16 (36%); stable, 12 (27%); and progression, 16 (37%). Median survival time for PFS and OS was 3.8 mo (95% CI: 2.5,5.6) and 9.2 mo (95% CI: 7.8, 14.4), respectively. In overall survival analysis, after adjusting for age, sex, P-16 status, and lymphocyte count, increased duration of treatment on ICI was associated with better OS (HR: 0.96, 95% CI: 0.88, 1.05, p=0.4). A separate model including CPS showed that CPS values of 1-20% and 21-100% had reduced hazard compared to CPS of 0% (HR: 0.24, 95% CI: 0.05, 1.31; HR: 0.06, 95% CI: 0.01, 0.58; respectively, LRT p=0.006).ConclusionWeekly PCC is an active treatment for RM-HNSCC pts that progressed on ICI. There is an association between positive CPS, longer duration of treatment on ICI, and increased OS.

"CGE24-096: Impact of Somatic Mutations on Outcomes of Salvage Radiation and Hormonal Therapy for Prostate Cancer Recurrence After Prostatectomy" published on 05 Apr 2024 by National Comprehensive Cancer Network.

Sarcomas comprise a wide range of diverse cancers of the bone and soft tissues, with ∼100 different types as classified by the World Health Organization.1,2 Sarcomas arise in any organ at any time, throughout the lifespan, and, depending on the specific type, can be treated with many known types of cancer therapies, including surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. Care teams thus require multidisciplinary pediatric and adult expertise.

Background and purpose: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. Materials and methods: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0–69.96). Results: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25–90%). The median dose homogeneity index was 1.07 (range: 1.03–1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0–75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. Conclusions: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

HPV viral E6 and E7 onco-proteins play a well-known role in carcinogenesis. Host genomic alterations also play a key role in the development of HPV-related oropharyngeal cancer and have been under-recognized. We describe a case series of 6 metastatic/locoregionally recurrent HPVOPSCC patients with FGFR alterations. HPVOPSCC presents with distinct pattern of spread both temporally and sites of recurrence compared to  non-HPV-related oropharyngeal cancer. Identification and reporting of genomic alterations in HPV are crucial to the understanding of disease biology and could aid in development of novel therapeutics for these patients. In addition, use of circulating tumor DNA may lead to early detection and supplement imaging in the follow up of these patients. Loco-regional treatments may also play a key role in the management of metastatic HPV OPSCC depending on the pattern of presentation. Our case series highlights all these novelties that could lead to better treatment outcomes.

Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases.