{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:26:11Z","timestamp":1788909971749,"version":"build-2803163510"},"reference-count":9,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,2,17]]},"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurrence within local nodal basins without improving overall survival or quality of life. However, the study was conducted prior to the current era of adjuvant systemic therapies and when CLND was the standard approach for microscopic nodal disease. As such, there is currently no data on the role of adjuvant RT in patients with melanoma who recur during or after adjuvant immunotherapy, including those that may or may not have undergone prior CLND. In this study, we aimed to answer this question.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with resected stage III melanoma who received adjuvant anti-programmed cell death protein-1 (PD-1) (\u00b1ipilimumab) immunotherapy with a subsequent locoregional (lymph node and\/or in-transit metastases) recurrence were retrospectively identified. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was rate of subsequent locoregional recurrence; secondary outcomes were locoregional recurrence-free survival (lr-RFS2) and overall RFS (RFS2) to second recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 71 patients were identified: 42 (59%) men, 30 (42%) BRAF V600E mutant, 43 (61%) stage IIIC at diagnosis. Median time to first recurrence was 7 months (1\u201344), 24 (34%) received adjuvant RT and 47 (66%) did not. Thirty-three patients (46%) developed a second recurrence at a median of 5 months (1\u201322). The rate of locoregional relapse at second recurrence was lower in those who received adjuvant RT (8%, 2\/24) compared with those who did not (36%, 17\/47, p=0.01). Adjuvant RT at first recurrence was associated with an improved lr-RFS2 (HR 0.16, p=0.015), with a trend towards an improved RFS2 (HR 0.54, p\n                      <jats:italic>=<\/jats:italic>\n                      0.072) and no effect on risk of distant recurrence or overall survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study to investigate the role of adjuvant RT in patients with melanoma with locoregional disease recurrence during or after adjuvant anti-PD-1-based immunotherapy. Adjuvant RT was associated with improved lr-RFS2, but not risk of distant recurrence, demonstrating a likely benefit in locoregional disease control in the modern era. Further prospective studies are required to validate these results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2022-006629","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T09:06:38Z","timestamp":1678266398000},"page":"e006629","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-8467","authenticated-orcid":false,"given":"Prachi","family":"Bhave","sequence":"first","affiliation":[{"name":"Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, Australia"},{"name":"Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Hong","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-5544","authenticated-orcid":false,"given":"Serigne N","family":"Lo","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Johnson","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Mangana","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Z\u00fcrich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgecan","family":"Dulgar","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Malignancy, Moffitt Cancer Center, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-7030","authenticated-orcid":false,"given":"Zeynep","family":"Eroglu","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Malignancy, Moffitt Cancer Center, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ling","family":"Yeoh","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Haydon","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg C","family":"Lodde","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Livingstone","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Khattak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"K\u00e4hler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Schleswig-Holstein - Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Hausschild","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Schleswig-Holstein - Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant A","family":"McArthur","sequence":"additional","affiliation":[{"name":"Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Maxwell","family":"Menzies","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Long","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"},{"name":"Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, Australia"},{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo S","family":"Carlino","sequence":"additional","affiliation":[{"name":"Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, Australia"},{"name":"Melanoma Institute Australia, Sydney, New South Wales, Australia"},{"name":"Department of Medical Oncology, Blacktown Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"2025100308571011000_11.3.e006629.1","doi-asserted-by":"crossref","first-page":"v533","DOI":"10.1093\/annonc\/mdz255","article-title":"Adjuvant nivolumab (NIVO) versus ipilimumab (IPI) in resected stage III\/IV melanoma: 3-year efficacy and biomarker results from the phase III checkmate 238 trial","volume":"30","author":"Weber","year":"2019","journal-title":"Ann 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survival outcomes of complete lymph node dissection in melanoma patients with positive sentinel node","volume":"36","author":"Leiter","year":"2018","journal-title":"JCO"},{"key":"2025100308571011000_11.3.e006629.8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1200\/JCO.22.00533","article-title":"Adjuvant therapy of nivolumab combined with ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or stage IV melanoma (checkmate 915)","volume":"41","author":"Weber","year":"2023","journal-title":"J Clin Oncol"},{"key":"2025100308571011000_11.3.e006629.9","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2022.40.16_suppl.9575","article-title":"Efficacy and safety of \u201csecond adjuvant\u201d therapy with BRAF\/MEK inhibitors after resection of recurrent melanoma following adjuvant PD-1\u2013based immunotherapy","volume":"40","author":"Taylor","year":"2022","journal-title":"JCO"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2022-006629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:57:18Z","timestamp":1759507038000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2022-006629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":9,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,8]]},"published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1136\/jitc-2022-006629"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2022-006629","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3]]}}}