PMID- 36367724 OWN - NLM STAT- MEDLINE DCOM- 20221115 LR - 20230111 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 5 IP - 11 DP - 2022 Nov 1 TI - Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. PG - e2241538 LID - 10.1001/jamanetworkopen.2022.41538 [doi] LID - e2241538 AB - IMPORTANCE: 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. OBJECTIVE: To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURES: IMPT or IMRT with or without chemotherapy. MAIN OUTCOMES AND MEASURES: The main outcomes were the incidence of acute and chronic (present after >/=6 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 chi2 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. RESULTS: The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16-positive 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-positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .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 < .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects of grade 3 or greater, although there was a significant difference for chronic xerostomia of grade 2 or greater (6 IMPT [11%] vs 22 IMRT [10%]; P < .001). Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months. CONCLUSIONS AND RELEVANCE: 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. FAU - Youssef, Irini AU - Youssef I AD - Department of Radiation Oncology, SUNY Downstate Health Sciences University, Brooklyn, New York. FAU - Yoon, Jennifer AU - Yoon J AD - Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick. FAU - Mohamed, Nader AU - Mohamed N AD - Department of Radiation Oncology, SUNY Downstate Health Sciences University, Brooklyn, New York. AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Zakeri, Kaveh AU - Zakeri K AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Press, Robert H AU - Press RH AD - New York Proton Center, New York. FAU - Chen, Linda AU - Chen L AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Gelblum, Daphna Y AU - Gelblum DY AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - McBride, Sean M AU - McBride SM AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Tsai, Chiaojung Jillian AU - Tsai CJ AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Riaz, Nadeem AU - Riaz N AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Yu, Yao AU - Yu Y AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Cohen, Marc A AU - Cohen MA AD - Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Dunn, Lara Ann AU - Dunn LA AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Ho, Alan L AU - Ho AL AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Wong, Richard J AU - Wong RJ AD - Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Michel, Loren S AU - Michel LS AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Boyle, Jay O AU - Boyle JO AD - Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Singh, Bhuvanesh AU - Singh B AD - Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Kriplani, Anuja AU - Kriplani A AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Ganly, Ian AU - Ganly I AD - Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Sherman, Eric J AU - Sherman EJ AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Pfister, David G AU - Pfister DG AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Fetten, James AU - Fetten J AD - Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Lee, Nancy Y AU - Lee NY AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20221101 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 SB - IM EIN - JAMA Netw Open. 2022 Dec 1;5(12):e2250485. PMID: 36538332 MH - Male MH - Humans MH - Female MH - Middle Aged MH - *Radiotherapy, Intensity-Modulated/adverse effects/methods MH - *Proton Therapy/adverse effects/methods MH - Radiotherapy Dosage MH - Retrospective Studies MH - Prospective Studies MH - *Papillomavirus Infections/complications MH - Neoplasm Recurrence, Local/etiology MH - *Oropharyngeal Neoplasms/radiotherapy/pathology MH - *Xerostomia/etiology MH - *Carcinoma PMC - PMC9652753 COIS- Conflict of Interest Disclosures: Dr Dunn reported receiving research support from and serving on the advisory board for Regeneron, serving on the advisory board for Merck, and receiving research funding from Eisai, CUE-101, Replimune, and Nektar outside the submitted work. Dr Ho reported receiving grants from and serving on clinical trial advisory boards for Eisai, Merck, Kura Oncology, and Ayala; receiving personal fees from and serving on advisory boards for Rgenta, Exelixis, Prelude Therapeutics, and Remix; receiving grants, consulting for, and receiving speaking fees from Elevar Therapeutics; receiving personal fees for serving on the data and safety monitoring committee from Affyimmune; consulting for Cellestia; receiving personal and speaking fees from CFS and Clinical Endocrinology Update; receiving personal fees from and consulting for McGivney Global Advisors; and receiving clinical trial grants from Novartis, Bayer, Genentech, AstraZeneca, and Bristol Myers Squibb outside the submitted work. Dr Singh reported serving on the scientific advisory board for CinRx outside the submitted work and having a US patent licensed to CinRx. Dr Sherman reported receiving personal fees from Eisai and Eli Lilly & Company outside the submitted work. Dr Pfister reported receiving grants from the National Institutes of Health (NIH), the Dimon Foundation, and the Serra Fund during the conduct of the study and receiving grants from Hookipa and personal fees from Nykode outside the submitted work. Dr Lee reported serving on advisory boards for Merck, Merck EMD, ELSIE, and Mirati Pharmaceuticals. No other disclosures were reported. EDAT- 2022/11/12 06:00 MHDA- 2022/11/16 06:00 PMCR- 2022/11/11 CRDT- 2022/11/11 11:32 PHST- 2022/11/11 11:32 [entrez] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/16 06:00 [medline] PHST- 2022/11/11 00:00 [pmc-release] AID - 2798320 [pii] AID - zoi221174 [pii] AID - 10.1001/jamanetworkopen.2022.41538 [doi] PST - epublish SO - JAMA Netw Open. 2022 Nov 1;5(11):e2241538. doi: 10.1001/jamanetworkopen.2022.41538.