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.
PURPOSE Patients with BRAF-mutant melanoma brain metastases (MBM) continue to have limited overall survival (OS), averaging 4 months, despite advancements in systemic therapies. Our study aims to identify patient-specific and treatment-related prognostic factors in BRAF-mutant MBM to inform treatment sequencing and patient selection in future studies and improve patient outcomes. METHODS The following data were manually curated from 100 patients with BRAF-mutant MBM diagnosed from 2009-2018, with primary cutaneous melanoma and who received initial MBM treatment at our institution: clinical and demographic, treatment, and OS outcomes. We compared OS with the log rank test using the Python package kaplanmeier between the various clinical, demographic and treatment (including treatment sequence) related variables. RESULTS Both elevated lactase dehydrogenase (LDH) was associated with shorter OS (p=0.023), as was leptomeningeal disease (p<0.001). Gender (male vs. female) and initial treatment modality (BRAFi vs. immunotherapy) did not significantly impact OS, (p=0.911 and 0.578, respectively). Breakthrough brain metastases were associated with shorter OS for patients who received initial systemic therapy for MBM (p<0.001), but breakthrough metastases did not significantly impact OS for the whole cohort (p=0.141). Additionally, patients who received BRAFi before MBM diagnosis had shorter OS (p=0.028). CONCLUSION In conclusion, we have identified some interesting relationships between OS and the sequencing of treatment modalities, as well as the timing of MBM presentation. These findings support further investigation of treatment sequencing to improve outcomes and the consideration of clinical variables, disease presentation, and treatment history to help refine patient selection for future trials for patients with BRAF-mutant MBM.
9540 Background: The management and OS of pts with metastatic melanoma have improved due to new systemic therapies. However, relatively little is known about the use of these treatments (tx) and their association with OS in pts with MBMs. We reviewed a large cohort of MBM pts to assess how pt demographics, disease characteristics, and MBM tx impact OS in the current era. Methods: Under an institutional review board-approved protocol, retrospective data were curated and analyzed from pts diagnosed with, and received tx for, MBM from 2014 to 2018 at the MD Anderson Cancer Center (MDA). Pts diagnosed with uveal or mucosal melanoma or other cancers were excluded. Pt demographics; timing and features of initial melanoma dx; timing and features of initial MBM dx; prior, initial and subsequent tx; and OS were collected. OS was determined from MBM dx to last clinical follow-up (FU). Pts alive at last FU were censored. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable (MV) associations of OS with variables of interest were investigated with Cox proportional hazards models. Initial treatment of MBM was assessed as a time-varying covariate. All statistical tests used a significance level of 5%. Results: A total of 401 MBM pts were identified. The median age at MBM dx was 61; 67% were male and 46% had a BRAF V600 mutation. At MBM diagnosis dx, most (70%) pts were asymptomatic; 70% had concurrent uncontrolled extracranial disease; 36% had elevated serum LDH. Prior tx included immunotherapy (IMT) for 39% and targeted therapy (TTX) for 17%. The median number of MBMs was 2; 31% had > 3 MBMs. Median largest MBM diameter was 1.0 cm, 9% had MBM > 3.0 cm, and 5% had concurrent leptomeningeal disease (LMD). Tx received after MBM dx included stereotactic radiosurgery (SRS; 53% as initial tx for MBM, 67% at any time after MBM dx), whole brain radiation therapy (WBRT; 16%, 35%), craniotomy (12%, 19%), IMT (37%, 74%), and/or TTX (22%, 40%). 31% received steroids during initial MBM tx. At a median FU of 13.4 (0.0 - 82.8) months (mos), the median OS was 15.1 mos, and 1- and 2-year OS rates were 56% and 40%. Notably, gender, time to MBM dx, and BRAF status were not associated with OS (univariate analysis). On MV analysis, clinical features associated with worse OS included increased age, increased primary tumor thickness, elevated LDH, > 3 MBMs, +LMD, +symptoms, and prior tx with IMT. Among tx used at any time after MBM dx, WBRT (HR 1.9, 95% CI 1.5-2.5) was associated with worse OS; SRS (HR 0.7, 95% CI 0.5-0.8) and IMT (HR 0.6, 95% CI 0.5-0.8) were associated with improved OS. Conclusions: In one of the largest cohorts of MBM pts described to date, OS has improved in MBM pts in the current era. Prognostic factors for OS include pt age, primary tumor and MBM features, prior tx, and tx for MBM. Additional analyses to assess the interaction of tx, disease features, and OS will be presented.
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