{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T21:04:29Z","timestamp":1772831069397,"version":"3.50.1"},"reference-count":53,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2020,5,3]],"date-time":"2020-05-03T00:00:00Z","timestamp":1588464000000},"content-version":"unspecified","delay-in-days":2,"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":[[2020,3,30]]},"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Immune checkpoint inhibition (ICI) is an essential treatment option in melanoma. Its outcome may be improved by a preceding radiation of metastases. This study aimed to investigate the impact of a preceding radiotherapy on the clinical outcome of ICI treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This multicenter retrospective cohort study included patients who received anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or anti-programmed cell death protein 1 (PD-1) ICI with or without preceding radiotherapy for unresectable metastatic melanoma. ICI therapy outcome was measured as best overall response (BOR), progression-free (PFS) and overall survival (OS). Response and survival analyses were adjusted for confounders identified by directed acyclic graphs. Adjusted survival curves were calculated using inverse probability treatment weighting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>835 patients who received ICI (anti-CTLA-4, n=596; anti-PD-1, n=239) at 16 centers were analyzed, whereof 235 received a preceding radiotherapy of metastatic lesions in stage IV disease. The most frequent organ sites irradiated prior to ICI therapy were brain (51.1%), lymph nodes (17.9%) and bone (17.9%). After multivariable adjustment for confounders, no relevant differences in ICI therapy outcome were observed between cohorts with and without preceding radiotherapy. BOR was 8.7% vs 13.0% for anti-CTLA-4 (adjusted relative risk (RR)=1.47; 95% CI=0.81 to 2.65; p=0.20), and 16.5% vs 25.3% for anti-PD-1 (RR=0.93; 95% CI=0.49 to 1.77; p=0.82). Survival probabilities were similar for cohorts with and without preceding radiotherapy, for anti-CTLA-4 (PFS, adjusted HR=1.02, 95% CI=0.86 to 1.25, p=0.74; OS, HR=1.08, 95% CI=0.81 to 1.44, p=0.61) and for anti-PD-1 (PFS, HR=0.84, 95% CI=0.57 to 1.26, p=0.41; OS, HR=0.73, 95% CI=0.43 to 1.25, p=0.26). Patients who received radiation last before ICI (n=137) revealed no better survival than those who had one or more treatment lines between radiation and start of ICI (n=86). In 223 patients with brain metastases, we found no relevant survival differences on ICI with and without preceding radiotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study detected no evidence for a relevant favorable impact of a preceding radiotherapy on anti-CTLA-4 or anti-PD-1 ICI treatment outcome in metastatic melanoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2019-000395","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T13:42:44Z","timestamp":1588686164000},"page":"e000395","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct01497808","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02303990","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Sarah","family":"Knispel","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Stang","sequence":"additional","affiliation":[{"name":"Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hildegard","family":"Lax","sequence":"additional","affiliation":[{"name":"Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Gutzmer","sequence":"additional","affiliation":[{"name":"Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Heinzerling","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Erlangen, Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Weishaupt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Pf\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Saarland University Medical Center, Homburg\/Saar, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Gesierich","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Herbst","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Helios Klinikum Erfurt, Erfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina C","family":"Kaehler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Kiel, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Weide","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carola","family":"Berking","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ludwig-Maximilians University Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Loquai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center Mainz, Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Utikal","sequence":"additional","affiliation":[{"name":"Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, niversity Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Terheyden","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kaatz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Wald-Klinikum Gera, Gera, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Schlaak","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ludwig-Maximilians University Munich, Munich, Germany"},{"name":"Department of Dermatology, Skin Cancer Center at CIO Koeln\/Bonn, University Hospital Cologne, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kreuter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Helios St. Elisabeth Hospital Oberhausen, 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