{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:30:48Z","timestamp":1793431848878,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:00:00Z","timestamp":1793318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:00:00Z","timestamp":1793318400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Re\u2010irradiation (re\u2010RT) for recurrent head and neck cancer (HNC) can be potentially curative but is constrained by significant toxicity. Proton therapy may improve the therapeutic ratio. This multicenter phase 2 trial evaluated the safety and efficacy of proton re\u2010RT in patients with HNC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients received prior HNC radiotherapy at a dose of \u226540 gray (Gy). Salvage surgery and\/or systemic therapy before re\u2010RT were permitted. Considering clinical status, two pragmatic treatment approaches were used: fractionated re\u2010RT (F\u2010Re\u2010RT; 60\u201370 Gy) or QUAD shot re\u2010RT (QS\u2010Re\u2010RT; 14.8 Gy per cycle, up to four cycles; maximum total, 59.2 Gy). Primary end points were locoregional recurrence\u2013free rates at 12 months for F\u2010Re\u2010RT and at 6 months for QS\u2010Re\u2010RT, and a fixed\u2010time, binary proportion analyzed using 90% Clopper\u2013Pearson confidence intervals (CIs) and prespecified success thresholds (lower bound, &gt;55% and &gt;10%, respectively). Secondary end points included overall survival (OS), progression\u2010free survival, the cumulative incidence of distant metastasis and locoregional recurrence, clinician\u2010reported toxicity, and patient\u2010reported outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From July 2017 to November 2022, 85 patients received either F\u2010Re\u2010RT (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a057) or QS\u2010Re\u2010RT (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a028), with a median follow\u2010up of 38 months. The locoregional recurrence\u2013free rates were 71% (90% CI, 59%\u201381%) at 12 months for F\u2010Re\u2010RT and 76% (90% CI, 58%\u201389%) at 6 months for QS\u2010Re\u2010RT, surpassing prespecified success thresholds. The highest late toxicity attributable to re\u2010RT was grade 3 in 20% of patients, grade 4 in 11%, and grade 5 in 4%. The 5\u2010year OS rate was 29%, and the 5\u2010year progression\u2010free survival rate was 23%. Patient\u2010reported outcomes were stable at 1 year after F\u2010Re\u2010RT and after QS\u2010Re\u2010RT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Proton re\u2010RT demonstrated encouraging locoregional control and survival in heavily pretreated patients, although late toxicities remain important concerns (ClinicalTrials.gov identifier: NCT03217188).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70643","type":"journal-article","created":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:45:29Z","timestamp":1793429129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A multicenter, prospective, phase 2 trial on proton re\u2010irradiation for patients with previously treated head and neck cancer"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6119-0889","authenticated-orcid":false,"given":"Edward Christopher","family":"Dee","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah S.","family":"Kalman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Miami Cancer Institute Herbert Wertheim College of Medicine Florida International University  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"White","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Lin","sequence":"additional","affiliation":[{"name":"New York Proton Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphna Y.","family":"Gelblum","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2814-4482","authenticated-orcid":false,"given":"Yao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-5481","authenticated-orcid":false,"given":"Jung Julie","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Radiology Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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