Changes in outcomes and factors associated with survival in melanoma patients with brain metastases

Abstract

BACKGROUD Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients. METHODS Patients diagnosed with MBMs from 1/1/2009-12/31/2013 (Prior Era; PE) and 1/1/2014-12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA). RESULTS 791 MBM patients (PE, n=332; CE, n=459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9 – 12.4) and improved in the CE versus PE (14.4 vs. 10.3 months, P < .001). Elevated serum LDH was the only factor associated with worse OS in both PE and CE patients. Factors associated with survival in CE MBM patients included patient age, primary tumor Breslow thickness, prior immunotherapy, leptomeningeal disease (LMD), symptomatic MBMs, and whole brain radiation therapy (WBRT). Several factors associated with OS in the PE were not significant in the CE. RPA demonstrated that elevated serum LDH and prior immunotherapy treatment are the most important determinants of survival in CE MBM patients. CONCLUSIONS OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations.

A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

“…According to previous studies, owing to recent improvements in chemotherapy and radiotherapy, the OS of patients with MBM has increased from approximately 4–14 months 2,10 . However, our study revealed that the outcomes of patients with MBMs in Japan did not improve as significantly as reported in other studies.…”

Symptomatic brain metastases in melanoma

“…Clinically, corticosteroid exposure prior to initiation of ICI is strongly associated with worse outcomes 62–65 . In a study comparing the outcomes of patients with MBM in the pre‐immunotherapy era and the current immunotherapy era, the presence of symptoms in the pre‐immunotherapy era was not associated with a worse outcome 10 ; probably because almost all MBM patients fared poorly prior to the widespread use of ICI. Taken together, these data suggest that the inferior clinical outcomes of patients with symptomatic MBM may at least be partly due to corticosteroid use.…”

“…Combination ICI (ipilimumab and nivolumab) is standard of care for patients with MBM 8,9 . Despite substantially improved clinical outcomes for patients with asymptomatic MBM (response rates of 50%–60%, with median overall survival >5 years), patients with symptomatic MBM respond poorly to treatment with combination ICI (response rates of 15%–20%, with median overall survival <9 months) 7–10 . Patients with symptomatic MBM therefore represent a significant unmet clinical need.…”

Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care

“…With the differences in clinical prognosis between melanoma patients with LMD and those with parenchymal brain metastases (Hasanov et al, 2022; Raizer et al, 2008), it was clear early on that there was something very unique about the LMD tumors and their microenvironment. Single‐cell RNA sequencing (scRNAseq) approaches have recently been utilized to elucidate and compare the immune landscapes of leptomeningeal metastasis, parenchymal brain metastases, and extra‐cranial metastases.…”