{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:25:35Z","timestamp":1792765535186,"version":"4.5.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Standard preoperative radiotherapy (RT) for high-risk soft tissue sarcoma (STS) is delivered over 5 weeks, which can be a logistical challenge for patients.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the long-term toxic effects and clinical outcomes associated with a shorter 5-day, dose-equivalent preoperative RT regimen.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Phase 2, single-group nonrandomized trial with an initial cohort (April 2016 to May 2018) and expansion cohort (October 2018 to May 2023) at a single academic center in the US. Participants were patients with histologically confirmed extremity or trunk STS recommended to undergo standard preoperative RT and surgery. Patients with planned neoadjuvant systemic therapy who were enrolled in the expansion group were excluded from this analysis. Analysis was conducted September 2024 to August 2025.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n A total of 30 Gy in 5 fractions were delivered preoperatively.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was 2-year grade 2 or higher radiation toxic effects. Secondary end points included major wound complications (MWC), local failure, distant progression, and overall survival.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 110 patients were treated with preoperative RT and surgery (42 patients [38%] were aged 65-79 years; 64 [58%] were male; 75 had tumors of the lower extremity [68%], and 64 patients [58%] had high-grade disease). The initial cohort accrued 50 patients who underwent surgery. The expansion cohort accrued 83 patients; 60 of 83 were treated without neoadjuvant chemotherapy and were included. Median (IQR) follow-up was 37.3 (20.1-60.6) months, including 64.2 (36.3-74.1) months for the initial cohort and 30.0 (13.5-40.2) months for the expansion cohort. At 2 years, 14 of 74 evaluable patients (18.9%) developed grade 2 or higher toxic effects (10 patients [25.0%] for the initial cohort and 4 patients [11.8%] for the expansion cohort). MWCs occurred in 33 of 110 patients (30.0%); (17 [34.0%] for the initial cohort and 16 [26.7%] for the expansion cohort). Time to wound closure exceeded 6 months for 15 patients (13.6%), including 12 of 29 patients (41.4%) who underwent local tissue advancement flaps. Two-year local control adjusting for competing risk of death was 92.4% (95% CI, 86.3%-96.5%). There were 3 (2.7%) bone fractures and 5 (4.5%) amputations.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This nonrandomized clinical trial of ultrahypofractionated preoperative RT identified durable local control with MWC and favorable late grade 2 or higher toxic effects rates. Randomized data are necessary to differentiate the safety profiles of various fractionation regimens, especially duration of wound healing.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT02701153<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.50195","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T16:00:38Z","timestamp":1765987238000},"page":"e2550195","source":"Crossref","is-referenced-by-count":7,"title":["Five-Day Preoperative Radiation Therapy for Patients With High-Risk Soft Tissue Sarcoma"],"prefix":"10.1001","volume":"8","author":[{"given":"John","family":"Nikitas","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of California, Los Angeles"},{"name":"Department of Radiation Oncology, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph 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