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However, this advantage is tempered by uncertainties, including range uncertainty and variable relative biological effectiveness. In this review, the authors summarize contemporary evidence supporting proton therapy across pediatric, central nervous system (CNS), head and neck, thoracic, breast, gastrointestinal, genitourinary, and hematologic malignancies, as well as reirradiation. The strength of evidence varies substantially by disease site. Proton therapy is well established in pediatric cancers and selected CNS tumors, where minimizing integral dose and late toxicity is especially important. Randomized trials have demonstrated clinically meaningful benefits in selected settings, including improved disease control and survival with proton craniospinal irradiation for leptomeningeal metastases and reduced toxicity with preserved disease control and survival benefit in oropharyngeal cancer. Conversely, randomized data in localized prostate cancer have not shown improved patient reported outcomes compared with intensity modulated photon therapy. Ongoing phase 3 trials across multiple disease sites are expected to further define the role of protons by clarifying comparative effectiveness, toxicity reduction, and cost\u2010effectiveness relative to advanced photon techniques. Future progress will depend on improved patient selection, robust treatment planning, and emerging technologies including adaptive proton therapy, proton arc therapy, and FLASH radiotherapy.<\/jats:p>","DOI":"10.1002\/cncr.70622","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:55:24Z","timestamp":1791960924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolving role of proton therapy in contemporary oncology"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6614-0212","authenticated-orcid":false,"given":"Emily S.","family":"Lebow","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-9726","authenticated-orcid":false,"given":"Helen A.","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Mass General Brigham Cancer Institute Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"Proton beam or intensity\u2010modulated radiation therapy in preserving brain function in patients with IDH mutant grade II or III glioma(NRG\u2010BN005; NCT03180502). 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