Abstract Background Pilomyxoid astrocytoma (PMA) is a subtype of pilocytic astrocytoma (PA) that occurs during infancy, arises in the hypothalamic/chiasmatic region, has a propensity for cerebrospinal dissemination, and carries a poorer prognosis compared to classic PA. The WHO 2021 classification recognizes PMA as a variant of PA, albeit cautioning that this rare variant tends to exhibit aggressive behavior. The rarity and categorization of this tumor within PAs has impeded broad molecular characterization, registry-based efforts, and clinical studies with sufficiently long follow-up periods. As such, there is no standardized treatment for children suffering considerably from this disease. Methods This is a case report of a 5-month-old male with profound failure-to-thrive and nystagmus, who was found to have a uniformly contrast-enhancing mass centered in the hypothalamus with extensive leptomeningeal metastases. Diagnostic biopsy demonstrated a low-grade astrocytoma with 2-5 mitoses per high-power field, perivascular rosettes, microvascular proliferation, myxoid changes, and an absence of Rosenthal fibers, consistent with PMA. Molecular testing demonstrated the BRAF KIAA1549 fusion event. The patient was treated with a novel combination of thioguanine, procarbazine, lomustine, vincristine (TPCV as per the Children’s Oncology Group Protocol A9952) and trametinib 0.032 mg/kg/day. Results The patient achieved partial response per pLGG RAPNO criteria (50% reduction in the target lesion) 6 months into therapy. Clinically, he gained weight, met milestones, and regained vision through therapy. He had one episode of central-line associated bloodstream infection, treated with antibiotics and line removal, but otherwise experienced minimal adverse events: no episodes of severe neutropenia, transfusion-dependent anemia or thrombocytopenia, hepatotoxicity, retinal toxicity, or cardiac toxicity. He experienced minor trametinib associated adverse effects including one episode of toe paronychia treated topically, eczematous rashes treated with triamcinolone, and low-grade, asymptomatic CK elevation. Conclusion Combination TPCV and trametinib may be a safe and effective combinatorial approach for young children with BRAF fusion-positive PMA.
Garner et al. (Fri,) studied this question.