Metastatic melanoma: prognostic factors and survival in patients with brain metastases

E Frinton,D Tong,J Tan,R E Board,S Kennedy,V Kumar,G Read,C Lim

doi:10.1007/s11060-017-2591-9

Abstract

Brain metastases from malignant melanoma carry a poor prognosis. Novel systemic agents have improved overall survival (OS), but the value of whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) remains uncertain. The melanoma-specific graded prognostic assessment (msGPA) provides useful prognostic information, but the relevance to the modern-day population has not been validated. Since 2011, 53 patients received treatment for brain metastases from malignant melanoma at the Rosemere Cancer Centre medical oncology clinic. Data were collated on demographic factors and survival. Survival analyses were performed using Kaplan–Meier methods. Cox regression was used to identify prognostic factors on univariate and multivariate analysis. OS from the date of diagnosis of brain metastases was 4.83 months (range 0.27–30.4 months). On univariate analysis, BRAF, performance status and msGPA were significant prognostic indicators for OS (p = 0.0056, p = 0.0039 and p = 0.0001 respectively). msGPA remained significant on multivariate analysis (p = 0.0006). OS for BRAF-positive patients receiving targeted treatment (n = 22) was significantly better than for BRAF-negative patients (n = 26), with median survival times of 8.2 and 3.7 months respectively (p = 0.0039, HR 2.36). SRS combined with systemic agents (n = 16) produced an OS of 13.5 months. Patients receiving WBRT alone (n = 21) had a poor prognosis (2.2 months). The msGPA remains a valid prognostic indicator in the era of novel systemic treatments for melanoma. BRAF-positive patients receiving targeted agents during their treatment had favorable survival outcomes. WBRT alone should be use with caution in the active management of melanoma brain metastases.

Highlights

Malignant melanoma is the fifth most common cancer in the UK
For survival analysis according to BRAF status, a further five patients were excluded due to unknown BRAF status
BRAF-mutant positive patients had significantly better survival times than the BRAF-mutant negative group, at 8.23 month median overall survival (OS) and 3.7 months respectively (p = 0.0039) from the time of diagnosis of brain metastases (Fig. 1)

Summary

Introduction

Malignant melanoma is the fifth most common cancer in the UK. the majority of patients present with early stage, operable disease, up to 20% have metastases at presentation [1]. Poor response rates to chemotherapy are most likely due to low drug concentrations accessing malignant cells owing to the protective nature of the blood–brain barrier [1]. There is evidence for the efficacy of novel systemic agents, both targeted BRAF inhibition and immunotherapy, in brain metastases from melanoma [1, 3,4,5]. Local treatment options include neurosurgery and radiotherapy. The latter is available for administration in two different forms; stereotactic radiosurgery (SRS) for patients with lowvolume, low count brain metastases [6], or whole brain radiotherapy (WBRT) for patients with more widely disseminated intracranial disease. The evidence base for the efficacy of WBRT in the treatment of melanoma brain metastases is inconclusive.

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