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.

Keywords: BRAF inhibitor; MEK inhibitor; brain metastasis; ependymal disease; leptomeningeal disease; melanoma; radiosurgery; whole brain radiation.

Figure 1

MRI image of progression of left temporoparietal metastasis. Contrast enhanced T1 MRI showing a 1.6 cm left temporoparietal lesion that increased in size after completion of whole brain radiation. This lesion was treated subsequently with stereotactic radiosurgery.

Figure 2

MRI images of ependymal disease and response to whole brain re-irradiation. (A) Contrast enhanced T1 MRI showing new enhancing, linear, and nodular lesions along the ventricles consistent with ependymal disease. (B) Contrast enhanced T1 MRI performed 2 months after whole brain re-irradiation showing a significant and rapid decrease in ependymal enhancement. The treated metastasis in the left temporoparietal area was stable. (C) Contrast enhanced T1 MRI performed 1 year after whole brain radiation showing resolution of nodular lesions along the ventricles and no new brain metastases.