Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG
Background 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.Methods This multicenter ret...
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000395.full |
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| author | Dirk Schadendorf Carola Berking Lucie Heinzerling Lisa Zimmer Ralf Gutzmer Alexander Kreuter Andreas Stang Elisabeth Livingstone Benjamin Weide Eleftheria Chorti Selma Ugurel Anja Gesierich Jürgen C Becker Peter Mohr Max Schlaak Patrick Terheyden Janine Gronewold Rudolf Herbst Carmen Loquai Sarah Knispel Hildegard Lax Carsten Weishaupt Claudia Pföhler Katharina C Kaehler Jochen Utikal Martin Kaatz Jens Ulrich Edgar Dippel Michael Weichenthal |
| author_facet | Dirk Schadendorf Carola Berking Lucie Heinzerling Lisa Zimmer Ralf Gutzmer Alexander Kreuter Andreas Stang Elisabeth Livingstone Benjamin Weide Eleftheria Chorti Selma Ugurel Anja Gesierich Jürgen C Becker Peter Mohr Max Schlaak Patrick Terheyden Janine Gronewold Rudolf Herbst Carmen Loquai Sarah Knispel Hildegard Lax Carsten Weishaupt Claudia Pföhler Katharina C Kaehler Jochen Utikal Martin Kaatz Jens Ulrich Edgar Dippel Michael Weichenthal |
| author_sort | Dirk Schadendorf |
| collection | DOAJ |
| description | Background 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.Methods 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.Results 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.Conclusions 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. |
| format | Article |
| id | doaj-art-88535c53b95b4637b1aed1641c90cbb3 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-88535c53b95b4637b1aed1641c90cbb32024-11-09T17:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000395Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOGDirk Schadendorf0Carola Berking1Lucie Heinzerling2Lisa Zimmer3Ralf Gutzmer4Alexander Kreuter5Andreas Stang6Elisabeth Livingstone7Benjamin Weide8Eleftheria Chorti9Selma Ugurel10Anja Gesierich11Jürgen C Becker12Peter Mohr13Max Schlaak14Patrick Terheyden15Janine Gronewold16Rudolf Herbst17Carmen Loquai18Sarah Knispel19Hildegard Lax20Carsten Weishaupt21Claudia Pföhler22Katharina C Kaehler23Jochen Utikal24Martin Kaatz25Jens Ulrich26Edgar Dippel27Michael Weichenthal28University Hospital of Essen, University Duisburg-Essen, NCT-West, Essen Campus, German Cancer Consortium, Partner Site Essen & University Alliance Ruhr, One Health Research Centre, Essen, Germany11 Department of Dermatology, Ludwig-Maximilians University Munich, Munich, GermanyDepartment of Dermatology and Allergology, Ludwig-Maximilian University, Munich, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Essen, GermanyDepartment of Dermatology, Muelenkreiskliniken Minden and Ruhr University Bochum, Minden, Germany6 Department of Dermatology and Allergology, HELIOS Sankt Elisabeth Klinik Oberhausen, Oberhausen, Nordrhein-Westfalen, Germany2 Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany20 Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, Germany1 Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany20 Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany7 Department of Dermatology, University Hospital Würzburg, Würzburg, Germany1 Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, Elbe Kliniken Buxtehude, Buxtehude, Germany11 Department of Dermatology, Ludwig-Maximilians University Munich, Munich, Germany14 Department of Dermatology, University Hospital Lübeck, Lübeck, GermanyDepartment of Neurology, University Hospital Essen, Essen, GermanyDepartment of Dermatology, HELIOS Hospital Erfurt, Erfurt, Germany2 Department of Dermatology, Johannes Gutenberg University Hospital Mainz, Mainz, Germany1 Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany2 Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital of Muenster, Muenster, Germany6 Department of Dermatology, Saarland University Medical Center, Homburg/Saar, Germany9 Department of Dermatology, University Hospital Kiel, Kiel, GermanyDKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, GermanyDepartment of Dermatology, DRK Hospital Chemnitz-Rabenstein, Rabenstein, GermanyDepartment of Dermatology and Allergy, Harzklinikum Dorothea Christiane Erxleben GmbH, Quedlinburg, GermanyDepartment of Dermatology, Ludwigshafen City Hospital, Ludwigshafen, GermanyDepartment of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein - Campus Kiel, Kiel, GermanyBackground 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.Methods 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.Results 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.Conclusions 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.https://jitc.bmj.com/content/8/1/e000395.full |
| spellingShingle | Dirk Schadendorf Carola Berking Lucie Heinzerling Lisa Zimmer Ralf Gutzmer Alexander Kreuter Andreas Stang Elisabeth Livingstone Benjamin Weide Eleftheria Chorti Selma Ugurel Anja Gesierich Jürgen C Becker Peter Mohr Max Schlaak Patrick Terheyden Janine Gronewold Rudolf Herbst Carmen Loquai Sarah Knispel Hildegard Lax Carsten Weishaupt Claudia Pföhler Katharina C Kaehler Jochen Utikal Martin Kaatz Jens Ulrich Edgar Dippel Michael Weichenthal Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG Journal for ImmunoTherapy of Cancer |
| title | Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG |
| title_full | Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG |
| title_fullStr | Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG |
| title_full_unstemmed | Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG |
| title_short | Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG |
| title_sort | impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma a multicenter retrospective cohort study of the decog |
| url | https://jitc.bmj.com/content/8/1/e000395.full |
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