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Eur J Cancer. 2019 Feb 7;110:11-20. doi: 10.1016/j.ejca.2018.12.023. [Epub ahead of print]

Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases.

Author information

1
Skin Cancer Center at the University Cancer Centre, Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
3
Skin Cancer Center at the University Cancer Centre, Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
4
Institute of Neuroradiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
5
Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.
6
Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany.
7
Skin Cancer Center, Department of Dermatology, University Hospital Tübingen, Tübingen, Germany.
8
Department of Radiation Oncology, Skin Cancer Center, CCC Tübingen-Stuttgart, University of Tübingen, Germany.
9
Skin Cancer Center, Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
10
Skin Cancer Center, Department of Dermatology and Allergy, University Hospital Munich, Munich, Germany.
11
Skin Cancer Center, Department of Dermatology, University Hospital Kiel, Kiel, Germany.
12
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
13
Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
14
Skin Cancer Center, Department of Dermatology, University of Lübeck, Lübeck, Germany.
15
Skin Cancer Center, Department of Dermatology and Venereology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
16
Skin Cancer Center, Department of Dermatology, Charité Universitätsmedizin Berlin, Berlin, Germany.
17
Skin Cancer Center, Department of Dermatology, Paracelsus Medical University, General Hospital Nuremberg, Germany.
18
Skin Cancer Center, Department of Dermatology, Ludwigshafen Medical Center, Ludwigshafen, Germany.
19
Skin Cancer Center, Department of Dermatology, Universitätsmedizin Greifswald, Greifswald, Germany.
20
Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
21
National Center for Tumor Diseases (NCT), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; Institute of Radiooncology - OncoRay, Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
22
Skin Cancer Center at the University Cancer Centre, Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: Friedegund.Meier@uniklinikum-dresden.de.

Abstract

BACKGROUND:

Combining stereotactic radiosurgery (SRS) and active systemic therapies (STs) achieved favourable survival outcomes in patients with melanoma brain metastases (MBMs) in retrospective analyses. However, several aspects of this treatment strategy remain poorly understood. We report on the overall survival (OS) of patients with MBM treated with a combination of radiotherapy (RT) and ST as well as the impact of the v-Raf murine sarcoma viral oncogene homolog B (BRAF)-V600 mutation (BRAFmut) status, types of RT and ST and their sequence.

PATIENTS AND METHODS:

Data of 208 patients treated with SRS or whole brain radiation therapy (WBRT) and either immunotherapy (IT) or targeted therapy (TT) within a 6-week interval to RT were analysed retrospectively. OS was calculated from RT to death or last follow-up. Univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic features associated with OS.

RESULTS:

The median follow-up was 7.3 months. 139 patients received IT, 67 received TT and 2 received IT and TT within 6 weeks to RT (WBRT 45%; SRS 55%). One-year Kaplan-Meier OS rates were 69%, 65%, 33% and 18% (P < .001) for SRS with IT, SRS with TT, WBRT with IT and WBRT with TT, respectively. Patients with a BRAFmut receiving IT combined with RT experienced higher OS rates (88%, 65%, 50% and 18%). TT following RT or started before and continued thereafter was associated with improved median OS compared with TT solely before RT (12.2 [95% confidence interval {CI} 9.3-15.1]; 9.8 [95% CI 6.9-12.6] versus 5.1 [95% CI 2.7-7.5]; P = .03).

CONCLUSION:

SRS and IT achieved the highest OS rates. A BRAFmut appears to be a favourable prognostic factor for OS. For the combination of RT and TT, the sequence appears to be crucial. Combinations of WBRT and ST achieved unprecedentedly high OS rates and warrant further studies.

KEYWORDS:

BRAF inhibitors; Brain metastases; Immune checkpoint inhibitors; Immunotherapies; Melanoma; Stereotactic radiosurgery; Targeted therapy; Whole brain radiation therapy

PMID:
30739835
DOI:
10.1016/j.ejca.2018.12.023
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