Targeted Therapy After Brain Radiotherapy for BRAF-Mutated Melanoma With Extensive Ependymal Disease With Prolonged Survival: Case Report and Review of the Literature

Abstract

Melanoma brain metastasis with ependymal spread/metastases is uncommon. These cases are frequently classified together with leptomeningeal disease. However, the commonalities and differences in the underlying pathophysiology and clinical outcomes between these two types of spread are not clear. Very few reports on long term outcome and durable central nervous system (CNS) disease control have been reported in the literature. Here, we report a case of a 45 year-old Caucasian lady with BRAF-V600E mutant metastatic melanoma to the brain who had whole brain radiotherapy followed by two Gamma knife radiosurgery treatments for localized disease progression. She then developed extensive ependymal disease progression with no evidence of leptomeningeal spread. She was treated with a repeat course of whole brain radiotherapy and maintained on BRAF and MEK inhibitors with durable CNS disease control for more than a year. This study reviews the management of BRAF-V600E mutant melanoma with ependymal involvement. Management using radiation therapy with maintenance targeted therapy seems to be a reasonable approach to this challenging disease.

Systemic therapy augmented by radiotherapy (STAR) effect for brain metastases in a BRAF-mutated melanoma patient with prolonged survival: a case report

“…Abu-Gheida et al [ 13 ] described the case of a 45-year-old woman with a BRAF -mutated melanoma with brain metastases. She received WBRT and two Gamma Knife SRS treatments for localized disease progression.…”

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

“…As many targeted therapy trials exclude patients with leptomeningeal involvement due to fears of rapid clinical deterioration, prospective trial data for the efficacy of targeted therapy in BRAF‐mutant melanoma patients with LMD does not exist. However, case reports have highlighted possible prolonged survival following treatment with targeted therapy for LMD (Abu‐Gheida et al, 2019; Arasaratnam et al, 2018; Floudas et al, 2016; Glitza et al, 2017; Kim et al, 2015; Lee et al, 2013; Schäfer et al, 2013; Wilgenhof & Neyns, 2015). Many of these reports describe a rapid response to therapy and well‐managed control of neurological symptoms.…”

“…noma patients with CNS disease. The initial results of the Phase II POLARIS trial (case reports have highlighted possible prolonged survival following treatment with targeted therapy for LMD(Abu-Gheida et al, 2019;Arasaratnam et al, 2018;Floudas et al, 2016;Kim et al, 2015;Lee et al, 2013;Schäfer et al, 2013;Wilgenhof & Neyns, 2015). Many of these reports describe a rapid response to therapy and well-managed control of neurological symptoms.…”

Multi-omics and tumor immune microenvironment characterization of a prognostic model based on aging-related genes in melanoma

“…The incidence of melanoma has increased rapidly over the past 30 years. According to U.S. cancer statistics, approximately 76,000 people were diagnosed with melanoma in 2017 in the United States [2]. The global annual death toll from melanoma is as high as 55,500 [3].…”