{"doi":"10.1001/jamanetworkopen.2021.13205","title":"Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy","abstract":"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.","journal":"JAMA Network Open","year":2021,"id":152615,"datarank":0.6476232170304466,"base_score":4.31748811353631,"endowment":4.31748811353631,"self_citation_contribution":0.6476232170304466,"citation_network_contribution":0.0,"self_endowment_contribution":0.6476232170304466,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":74,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":348656,"name":"Sarin Kitpanit","orcid":"0000-0003-3757-2865","position":1,"is_corresponding":false},{"id":293157,"name":"Anna Lee","orcid":"0000-0002-9114-1815","position":2,"is_corresponding":false},{"id":348657,"name":"Dennis Mah","orcid":"0000-0003-3644-0828","position":3,"is_corresponding":false},{"id":349684,"name":"Kevin Sine","orcid":null,"position":4,"is_corresponding":false},{"id":255786,"name":"Eric J. Sherman","orcid":"0000-0002-4960-4783","position":5,"is_corresponding":false},{"id":348658,"name":"Lara Dunn","orcid":"0000-0001-5318-2571","position":6,"is_corresponding":false},{"id":231265,"name":"Loren S. Michel","orcid":"0009-0000-1865-3315","position":7,"is_corresponding":false},{"id":491431,"name":"James Fetten","orcid":null,"position":8,"is_corresponding":false},{"id":512992,"name":"Kaveh Zakeri","orcid":"0000-0003-3921-480X","position":9,"is_corresponding":false},{"id":490682,"name":"Yao Yu","orcid":"0000-0002-2814-4482","position":10,"is_corresponding":false},{"id":490683,"name":"Linda Chen","orcid":"0000-0001-7078-163X","position":11,"is_corresponding":false},{"id":348653,"name":"Jung Julie Kang","orcid":"0000-0001-9773-5481","position":12,"is_corresponding":false},{"id":325305,"name":"Daphna Y. Gelblum","orcid":"0000-0001-7211-6246","position":13,"is_corresponding":false},{"id":255799,"name":"Sean M. McBride","orcid":"0000-0002-9676-1669","position":14,"is_corresponding":false},{"id":329130,"name":"C. Jillian Tsai","orcid":"0009-0004-8051-0787","position":15,"is_corresponding":false},{"id":236122,"name":"Nadeem Riaz","orcid":"0000-0001-9873-5862","position":16,"is_corresponding":false},{"id":255810,"name":"Nancy Y. Lee","orcid":"0000-0003-3044-9522","position":17,"is_corresponding":false},{"id":458333,"name":"Xingzhe Li","orcid":"0000-0002-8665-4704","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:43:34.972031Z","pmid":"34143193","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}