PMID- 34143193 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20220716 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 4 IP - 6 DP - 2021 Jun 1 TI - Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. PG - e2113205 LID - 10.1001/jamanetworkopen.2021.13205 [doi] LID - e2113205 AB - IMPORTANCE: Patients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC. OBJECTIVE: To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021. EXPOSURES: IMPT vs IMRT with or without chemotherapy. MAIN OUTCOMES AND MEASURES: The main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). RESULTS: We identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49 (63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months. On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08). Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly associated with both poor LRFS (HR, 63.37; 95% CI, 3.25-1236.13; P = .006) and poor PFS (HR, 6.33; 95% CI, 1.16-34.57; P = .03) on multivariable analyses. CONCLUSIONS AND RELEVANCE: In this study, curative-intent radiotherapy with IMPT for nonmetastatic NPC was associated with significantly reduced acute toxicity burden in comparison with IMRT, with rare late complications and excellent oncologic outcomes, including 100% locoregional control at 2 years. Prospective trials are warranted to direct the optimal patient selection for IMPT as the primary radiotherapy modality for nonmetastatic NPC. FAU - Li, Xingzhe AU - Li X AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Kitpanit, Sarin AU - Kitpanit S AD - Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. FAU - Lee, Anna AU - Lee A AD - Department of Radiation Oncology, Division of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas. FAU - Mah, Dennis AU - Mah D AD - ProCure Proton Therapy Center, Somerset, NJ. FAU - Sine, Kevin AU - Sine K AD - ProCure Proton Therapy Center, Somerset, NJ. FAU - Sherman, Eric J AU - Sherman EJ AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Dunn, Lara A AU - Dunn LA AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Michel, Loren S AU - Michel LS AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Fetten, James AU - Fetten J AD - Department of Medicine, 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 - Yu, Yao AU - Yu Y AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Chen, Linda AU - Chen L AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Kang, Jung Julie AU - Kang JJ 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 J 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 - 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 GR - R25 EB025787/EB/NIBIB NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210601 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 SB - IM CIN - JAMA Netw Open. 2021 Jun 1;4(6):e2113650. PMID: 34143197 EIN - JAMA Netw Open. 2021 Oct 1;4(10):e2135629. PMID: 34668953 MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Nasopharyngeal Carcinoma/*mortality/*therapy MH - Propensity Score MH - Proportional Hazards Models MH - Prospective Studies MH - Proton Therapy/*adverse effects/*methods MH - Radiotherapy, Intensity-Modulated/*adverse effects/*methods MH - Retrospective Studies MH - Survival Rate MH - Treatment Outcome MH - United States PMC - PMC8214161 COIS- Conflict of Interest Disclosures: Dr Dunn reported serving on the advisory Boards of Merck and Regeneron and receiving research funding from Regeneron, Eisai, and CUE Biopharma outside the submitted work. Dr McBride reported receiving honoraria and research funding from Janssen Pharmaceuticals, AstraZeneca, and Roche-Genentech. Dr Riaz reported receiving grants from Pfizer, REPARE Therapeutics, and Archer outside the submitted work. No other disclosures were reported. EDAT- 2021/06/19 06:00 MHDA- 2022/01/08 06:00 PMCR- 2021/06/18 CRDT- 2021/06/18 12:21 PHST- 2021/06/18 12:21 [entrez] PHST- 2021/06/19 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2021/06/18 00:00 [pmc-release] AID - 2781193 [pii] AID - zoi210396 [pii] AID - 10.1001/jamanetworkopen.2021.13205 [doi] PST - epublish SO - JAMA Netw Open. 2021 Jun 1;4(6):e2113205. doi: 10.1001/jamanetworkopen.2021.13205.