Characteristics of Patients Who Survived More than 5 Years after Diagnosis of Melanoma Brain Metastases

Abstract

<h3>Purpose/Objective(s)</h3> Patients with melanoma brain metastases (mBM) have historically demonstrated poor overall survival (OS). However, the prognosis of metastatic melanoma has improved dramatically in the era of immunotherapy. At our institution, we have a substantial cohort of patients who received intracranial RT and survived more than five years after diagnosis of mBM. We performed a descriptive study to characterize this cohort. <h3>Materials/Methods</h3> Patients who received intracranial RT for mBM at our institution were identified retrospectively. Those with OS greater than five years after diagnosis of mBM were included. Patient, disease, and treatment characteristics were collected. Kaplan-Meier analysis was used to estimate OS and intracranial progression-free survival (iPFS). Patients with histologically proven radiation necrosis (RN) were identified. <h3>Results</h3> Forty-five patients with 127 mBM at diagnosis received RT between 2006 and 2017 and survived more than 5 years. The median age at mBM diagnosis was 59 years (range, 32 to 73), and 69% were male. The primary tumor was cutaneous in 76% and unknown in 24%. BRAF V600 mutations were identified in 51% of patients. The median number of mBM at diagnosis was 2 (range, 1 to 14), and the median largest dimension was 2.3 cm (range, 0.3 to 5.4). Thirty-one mBM (24%) in 27 patients (60%) were resected prior to RT. Forty patients (89%) had stereotactic radiosurgery and 5 patients (11%) had whole brain RT as their initial RT modality. At mBM diagnosis, 31% had no evidence of disease (NED) extracranially. Most patients (91%) received immunotherapy. This was delivered concurrently with RT (47%), prior to RT (16%), or after RT (33%). At a median of 85 months of follow-up, 9 patients (20%) were deceased, including only 2 with clear evidence of intracranial progression, and 31 (69%) were alive and NED. Median OS was 156 months. Intracranial progression was observed in 19 patients (42%) at a median of 134 months. Histologically proven RN was identified in 11 patients (24%). <h3>Conclusion</h3> To our knowledge, these 45 patients constitute the largest report of mBM patients with OS exceeding 5 years. Most of this cohort was alive and NED at the time of analysis. The burden of intracranial disease at diagnosis was low, and a third of patients had no extracranial disease. Nearly all patients received immunotherapy, of whom half had immunotherapy concurrent with RT. Nearly half of patients who survived more than 5 years did so despite having intracranial progression after initial RT for their mBM. Nearly a quarter of patients had histologically proven RN, suggesting an enhanced immune response to RT in this cohort. Prior studies suggest a correlation between RN and increased intracranial response to RT. Future efforts should characterize the post-treatment radiographic features and other correlatives that differentiate this cohort from the general population with mBM. These results demonstrate an astounding outcome in some patients with limited volume mBM treated in the modern era.