{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:41:00Z","timestamp":1791492060387,"version":"4.3.4"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.<\/jats:p><\/jats:sec>Exposures<\/jats:title>IMPT or IMRT with or without chemotherapy.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The main outcomes were the incidence of acute and chronic (present after \u22656 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and \u03c72<\/jats:sup> tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.<\/jats:p><\/jats:sec>Results<\/jats:title>The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16\u2013positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16\u2013positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P<\/jats:italic>\u2009=\u2009.18), PFS (82% IMPT vs 85% IMRT; P<\/jats:italic>\u2009=\u2009.62), or LRR (5% IMPT vs 4% IMRT; P<\/jats:italic>\u2009=\u2009.59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P<\/jats:italic>\u2009&amp;lt;\u2009.001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P<\/jats:italic>\u2009&amp;lt;\u2009.001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P<\/jats:italic>\u2009&amp;lt;\u2009.001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P<\/jats:italic>\u2009&amp;lt;\u2009.001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P<\/jats:italic>\u2009=\u2009.003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P<\/jats:italic>\u2009=\u2009.04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P<\/jats:italic>\u2009&amp;lt;\u2009.001). There were no significant differences in chronic toxic effects except for xerostomia. Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.41538","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T16:33:13Z","timestamp":1668184393000},"page":"e2241538","source":"Crossref","is-referenced-by-count":50,"title":["Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy"],"prefix":"10.1001","volume":"5","author":[{"given":"Irini","family":"Youssef","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, SUNY Downstate Health Sciences University, Brooklyn, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Rutgers Cancer Institute of New 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