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

Abstract

Background: Melanoma 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). Methods: This 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. Results: One 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).

30-day mortality in patients treated for brain metastases: extracranial causes dominate

“…Most patients with brain metastases from extracranial primary tumors such as lung or breast cancer receive palliative treatment approaches, because the common pattern of polymetastatic spread may cause compromised performance status (PS) and eventually also limited survival, often in the range of 3–9 months [ 1 ]. Both, longer survival (typically if oligometastases are present [ 2 ]) and shorter survival may be observed, and considerable efforts have been undertaken to predict survival (nomograms, scores, online calculators [ 3 – 5 ]). Given that very short survival often is synonymous to active treatment in the last 30 days of life, oncologists can opt for palliative and supportive care rather than brain-directed therapy [ 6 ].…”

Management of intracranial melanoma metastasis with radiosurgery: a case report and literature review

“…Recent developments in immunotherapy, stereotactic radiosurgery, and fractionated stereotactic radiotherapy have significantly improved the survival rate; the advantage of this type of therapy over holocranial radiotherapy is the preservation of cognitive functions. However, it has been shown that only 25% of patients have access to said combined therapy 4,5 .…”

Improving Brain Metastases Outcomes Through Therapeutic Synergy Between Stereotactic Radiosurgery and Targeted Cancer Therapies

“…Schaule et al conducted a retrospective analysis of 110 patients treated with concurrent targeted or immunotherapy and stereotactic radiotherapy and found that cumulative brain metastases volume (p = 0.04), timing of metastases (syn-versus metachronous) (p = 0.01) and systemic therapy with concurrent immunotherapy (p = 0.005) significantly improved overall survival; with these findings they established a volume-timingsystemic therapy (VATS) score with point values ascribed to the aforementioned factors and median overall survival as of 34.5 months in patients with a VATS score of 2 (p = 0.03) (70).…”