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

被引：45

作者：

Rauschenberg, Ricarda ^{[1
,2
,3
,4
]}

Bruns, Johannes ^{[5
]}

Bruetting, Julia ^{[1
,2
]}

Daubner, Dirk ^{[2
,6
]}

Lohaus, Fabian ^{[2
,7
,8
,9
,10
,11
]}

Zimmer, Lisa ^{[12
]}

Forschner, Andrea ^{[13
]}

Zips, Daniel ^{[14
]}

Hassel, Jessica C. ^{[15
,16
]}

Berking, Carola ^{[17
]}

Kaehler, Katharina C. ^{[18
]}

Utikal, Jochen ^{[19
,20
]}

Gutzmer, Ralf ^{[21
]}

Terheyden, Patrik ^{[22
]}

Meiss, Frank ^{[23
]}

Rafei-Shamsabadi, David ^{[23
]}

Kiecker, Felix ^{[24
]}

Debus, Dirk ^{[25
]}

Dabrowski, Evelyn ^{[26
]}

Arnold, Andreas ^{[27
]}

Garzarolli, Marlene ^{[1
,2
,3
,4
]}

Kuske, Marvin ^{[1
,2
,3
,4
]}

Beissert, Stefan ^{[1
,2
,3
,4
]}

Loeck, Steffen ^{[2
,7
,8
,9
,10
,11
]}

Linn, Jennifer ^{[2
,7
]}

Troost, Esther G. C. ^{[2
,3
,4
,7
,8
,9
,10
,11
,28
]}

Meier, Friedegund ^{[1
,2
,3
,4
,8
,9
]}

机构：

[1] Tech Univ Dresden, Fac Med, Dept Dermatol, Univ Canc Ctr,Skin Canc Ctr, Dresden, Germany

[2] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[3] Natl Ctr Tumor Dis NCT, Dresden, Germany

[4] German Canc Res Ctr, Heidelberg, Germany

[5] Tech Univ Dresden, Fac Med Carl Gustav Carus, Dresden, Germany

[6] Tech Univ Dresden, Fac Med, Inst Neuroradiol, Dresden, Germany

[7] Tech Univ Dresden, Fac Med, Dept Radiotherapy & Radiat Oncol, Dresden, Germany

[8] German Canc Consortium DKTK, Partner Site Dresden, Heidelberg, Germany

[9] German Canc Res Ctr, Heidelberg, Germany

[10] Tech Univ Dresden, Helmholtz Zentrum Dresden Rossendorf, Fac Med, OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany

[11] Tech Univ Dresden, Helmholtz Zentrum Dresden Rossendorf, Univ Hosp Carl Gustav Carus, Dresden, Germany

[12] Univ Duisburg Essen, Univ Hosp, Dept Dermatol, Duisburg, Germany

[13] Univ Hosp Tubingen, Dept Dermatol, Skin Canc Ctr, Tubingen, Germany

[14] Univ Tubingen, CCC Tubingen Stuttgart, Skin Canc Ctr, Dept Radiat Oncol, Tubingen, Germany

[15] Univ Hosp Heidelberg, Dept Dermatol, Skin Canc Ctr, Heidelberg, Germany

[16] Univ Hosp Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[17] Univ Hosp Munich, Dept Dermatol & Allergy, Skin Canc Ctr, Munich, Germany

[18] Univ Hosp Kiel, Dept Dermatol, Skin Canc Ctr, Kiel, Germany

[19] German Canc Res Ctr, Skin Canc Unit, Heidelberg, Germany

[20] Ruprecht Karl Univ Heidelberg, Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, Mannheim, Germany

[21] Hannover Med Sch, Dept Dermatol & Allergy, Skin Canc Ctr Hannover, Hannover, Germany

[22] Univ Lubeck, Dept Dermatol, Skin Canc Ctr, Lubeck, Germany

[23] Univ Freiburg, Med Ctr, Fac Med, Skin Canc Ctr,Dept Dermatol & Venereol, Freiburg, Germany

[24] Charite Univ Med Berlin, Dept Dermatol, Skin Canc Ctr, Berlin, Germany

[25] Paracelsus Med Univ, Gen Hosp Nuremberg, Dept Dermatol, Skin Canc Ctr, Nurnberg, Germany

[26] Ludwigshafen Med Ctr, Dept Dermatol, Skin Canc Ctr, Ludwigshafen, Germany

[27] Univ Med Greifswald, Dept Dermatol, Skin Canc Ctr, Greifswald, Germany

[28] HZDR, Inst Radiooncol OncoRay, Dresden, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2019年 / 110卷

关键词：

Melanoma; Brain metastases; Stereotactic radiosurgery; Whole brain radiation therapy; Immunotherapies; Targeted therapy; Immune checkpoint inhibitors; BRAF inhibitors; STEREOTACTIC RADIOSURGERY; CEREBRAL METASTASES; CLINICAL-OUTCOMES; INHIBITOR THERAPY; CTLA-4; BLOCKADE; NRAS MUTATIONS; RADIOTHERAPY; IMMUNOTHERAPY; RADIONECROSIS; DETERMINANTS;

D O I：

10.1016/j.ejca.2018.12.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2019 The Author(s). Published by Elsevier Ltd.

引用

页码：11 / 20

页数：10

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