Case Presentation: Pediatric Low-Grade Glioma

A 5 year old obese female without other past medical history presented with 2 months of progressive headache and emesis. At the time of presentation, she was experiencing daily headaches and emesis for 4 days and dysconjugate gaze for 1 day. A head computed tomography (CT) at the emergency room revealed a suprasellar mass with obstructive hydrocephalus. The patient was then transferred to our hospital for urgent neurosurgical evaluation. 

MRI of the brain demonstrated a T2 hyperintense, predominantly solid, suprasellar mass measuring 4.3 x 3.5 cm located just posterior to the optic chiasm. She underwent a subtotal resection and was discharged after her hydrocephalus resolved with planned outpatient oncology follow up. Pathology demonstrated a diagnosis of juvenile pilocytic astrocytoma with a KIAA1549: BRAF fusion but no other abnormality. Given the partial resection, we offered several chemotherapy options including treatment with carboplatin and vincristine; thioguanine, procarbazine, lomustine, and vincristine (TPCV); monotherapy with vinblastine; as well as a clinical trial (NCT02840409). As the family lived over an hour away from our hospital and there was a national shortage of vincristine at that time, the decision was made to start treatment with weekly vinblastine which could be administered locally. 

She completed 1 year of therapy with vinblastine without significant toxicity and end of therapy scans demonstrated improved tumor bulk however, a 3-month off therapy scan demonstrated regrowth of the tumor and the team decided to start her on irinotecan with bevacizumab. Initially the patient was started on irinotecan alone until it was confirmed she would not require any neurosurgical procedures. She received her first dose of bevacizumab on day 15 of her first cycle but after asecond dose, developed hypertensive emergency requiring ICU admission. After she recovered, her treatment was switched to carboplatin and vincristine per CCG-A9952. The patient initially tolerated infusions well, but over time developed allergic reaction to carboplatin that did not resolve despite pre-medications and treatment had to be discontinued after 8 months. 

At that point, the decision was made to complete the remainder of her treatment with vinblastine, which she had previously tolerated, however vinblastine also had to be discontinued a few weeks early due to patient anxiety. Surveillance imaging and visual exams remained stable for >1 year off therapy but an 18-months off therapy MRI brain demonstrated recurrent growth of her tumor. Due to persistent hydrocephalus and visual exam concerning for papilledema, the patient underwent the placement of a venticuloperitoneal (VP) shunt. 

We discussed MEK inhibitors and RAF inhibitors with the family and the decision was made to start trametinib at this time. Given prior history of hypertension, the patient was started on a low dose (0.5 mg/day) of trametinib, which was increased to 1 mg daily after 3 months. She remains on this dose with some Grade 1 toxicities including facial rash that responded to clindamycin gel, CPK and creatinine elevation, mild upper extremity edema, and loose stools. MRI at 3 months demonstrated decreased tumor size. 

She continues to be closely followed by cardiology, neurosurgery, endocrinology, and ophthalmology.