Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy

Marcella Szuecs,S.g.c. Kroeze ,Klaus Henning Kahl ,An Claes,Fabian Lohaus,S. Adebahr ,Markus M. Schymalla,Stephanie E. Combs,Reinhard Dummer,Daniel Buergy,Michael Geier,Susanne Stera,Jana Schaule,Matthias Gückenberger ,Nora Sundahl,Oliver Blanck,David Kaul,Franziska Eckert,Guido Henke,N. Abbasi-Senger ,Falk Roeder

doi:10.1186/s13014-020-01558-8

Abstract

BackgroundMelanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT).MethodsThis retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS.ResultsOne hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0–40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03).ConclusionThe molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.

Highlights

The molecular graded prognostic assessment (molGPA) score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic Targeted therapy (TT)/IT
We propose a prognostic Volume – timing – systemic therapy (VTS) score, which needs to be validated prospectively
In a cohort of patients treated homogenously with concurrent IT/TT and stereotactic radiotherapy (SRT), other factors than those informing the molGPA score may be of improved prognostic power (Fig. 2). To our knowledge, this is the first study attempting to validate the molGPA score in a cohort of melanoma patients with brain metastases, which was homogeneously treated with concurrent SRT and targeted- or immunotherapy

Summary

Introduction

The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). We aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). Recent developments in the fields of targeted- and immunotherapy (TT/IT), as well as the widespread use of stereotactic radiosurgery (single fraction, SRS) and stereotactic radiotherapy (fractionated stereotactic radiotherapy, SRT) have significantly improved survival [3]. For a limited number of up to four brain metastases, SRT without WBRT is the preferred treatment option [12]. In the rapidly changing setting of treatment opportunities for melanoma patients it remains unclear, which patients benefit most from local treatment and there is a need for a reliable prognostic score to tailor treatment

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