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This trial assessed radiation therapy (RT) to the primary site after local excision.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009\u20132020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03\u20132.76; <jats:italic>p<\/jats:italic> = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&amp;N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1245\/s10434-024-15569-2","type":"journal-article","created":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T19:01:19Z","timestamp":1717873279000},"page":"6088-6096","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09)"],"prefix":"10.1245","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-728X","authenticated-orcid":false,"given":"Mark B.","family":"Pinkham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Herschtal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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B. Pinkham has received fees for professional services from Servier, Roche, Bristol-Myers Squibb, Astra Zenica, and Elekta. A. M. Hong has received fees for professional service from Telix. R. A. Scolyer has received fees for professional services from SkylineDx BV, IO Biotech ApS, MetaOptima Technology Inc., F. Hoffmann-La Roche Ltd, Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc., Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline. C. A. Barker leads clinical trials supported by Elekta, Merck, Amgen, EMD Serono, Alpha Tau Medical, and Regeneron for which his institution has received funding. He has served as a paid scientific advisor to Regeneron and as an unpaid scientific advisor to Castle Biosciences. M. C. Foote has received fees for professional services from Elekta and Varian. The remaining authors have no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}