Case Presentation: Late Progression of BRAF Fusion-Positive Pediatric Low-Grade Brainstem Glioma Following Chemotherapy

A 5-year-old female presented with facial nerve palsy, nystagmus, emesis, and intermittent headaches for 6 to 7 months. The patient was evaluated in a local emergency room, where an MRI of the brain demonstrated a lesion in the right dorsal pons and the middle cerebellar peduncle, with an exophytic component in the cerebellopontine angle cistern. The patient underwent a right cerebellar stereotactic biopsy. Pathology demonstrated a pilomyxoid astrocytoma, WHO grade II. 

Figure. Coronal T1 post contrast MRI brain (left panel) and axial T1 post contrast MRI brain (right panel) demonstrating a partially contrast-enhancing right cerebellar pontine region mass causing mass effect on the brainstem and fourth ventricle.

Given the morbidity associated with surgery, adjuvant systemic therapy was initiated with carboplatin/vincristine per the Children’s Oncology Group A9952 study. The patient developed a carboplatin allergy after 5 cycles and hence was switched to an alternative chemotherapy regimen with vinblastine, which the patient received for a total of 12 months. The patient achieved a good radiographic and clinical response to treatment and was subsequently followed with surveillance imaging and neurological exams. She remained clinically well with no evidence of tumor regrowth/recurrence. 

Approximately 3.5 years post-chemotherapy (nearly 5.5 years from diagnosis), the patient developed headaches, blurry vision, and increased fatigue. An ophthalmologic exam demonstrated papilledema and an MRI of the brain demonstrated progression of the exophytic component of the tumor along with obstructive hydrocephalus. She subsequently underwent ventriculoperitoneal shunt (VPS) placement. Cerebrospinal fluid (CSF) from VPS was negative for tumor cells. MRI total spine demonstrated no evidence of disseminated disease. Molecular testing of the tumor (next-generation sequencing) demonstrated a KIAA1549-BRAF fusion. 

The patient then started treatment with a MEK inhibitor. However, treatment was complicated by multiple adverse side effects (grade 3 acneiform skin rash, generalized fatigue, myopathy with elevation of creatine phosphokinase/CPK; grade 2 gastrointestinal symptoms, and diarrhea requiring treatment, which led to a treatment interruption followed by dose reduction to mitigate toxicity. An MRI of the brain four months after starting treatment with the MEK inhibitor demonstrated a 20% reduction in tumor size. Despite the initial good response, the patient subsequently discontinued treatment due to ongoing toxicities. This was accompanied by tumor regrowth; however, the patient remained without obvious new or worsening neurological symptoms.