Brain stem tumors in children less than 3 months: Clinical and radiologic findings of a rare disease.

PURPOSE: Brain stem tumors in children < 3 months at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management. METHODS: This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers, including patients with a brainstem tumor diagnosed between 2009 and 2020 and aged < 3 months at diagnosis. Clinical data were collected, and imaging characteristics were analyzed blindly and independently by two neuroradiologists. RESULTS: Five cases were identified. No patient received any therapy. The epicenter of two tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in three. For patients with tumor in equal parts in the medulla oblongata and the pons (n = 3), the extension at diagnosis involved the spinal cord; for the two patients with the tumor epicenter in the medulla oblongata alone (n = 2), the extension at diagnosis included the pons (n = 2) and the spinal cord (n = 1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died. In one patient, autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n = 2) or stable disease (n = 1). Survivors were followed up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma. CONCLUSIONS: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management.

Targeted therapy for pediatric low-grade glioma.

PURPOSE: Pediatric low-grade gliomas are the most frequent brain tumors in children. The standard approach for symptomatic unresectable tumors is chemotherapy. Recently, key molecular alterations/pathways have been identified and targeted drugs developed and tested in clinical trials. We describe our institutional experience with MAPK pathway targeted therapy. METHODS: We retrospectively reviewed the medical reports of 23 patients diagnosed with PLGG and treated with either trametinib or dabrafenib at Hospital Sant Joan de Dèu (Barcelona, Spain). Patients with neurofibromatosis were excluded. Objective response rate (ORR) and disease control rate (DCR) were determined using the Response Assessment in Pediatric Neuro-Oncology criteria in low-grade glioma. ORR was defined as the proportion of patients with the best overall response including complete remission (CR) or partial remission (PR). DCR was the sum of the CR, PR, and stable disease (SD) rates. RESULTS: ORR with trametinib was 0% (95% CI, 0%-23.2%) and DCR was 78.6% (95% CI, 49.2%-95.3%). Eleven patients had SD and three patients presented PD. ORR with dabrafenib was 41.7% (95% CI, 16.5%-71.4%), including four CR and one patient with PR. DCR with dabrafenib was 100% (95% CI, 73.5%-100%); there were seven SD and none PD. Treatment was well tolerated. Only three patients, on trametinib, presented grade 3 adverse effects: leukocytoclastic vasculitis, cheilitis, and bone infection. CONCLUSIONS: Our experience adds to the growing data about the efficacy and tolerability of targeted therapy in patients with PLGG. When present, toxicity is mainly mild-moderate and transient. Ongoing prospective clinical trials are trying to address if its use should be advanced to first-line therapy.

Treatment response of CNS high-grade neuroepithelial tumors with MN1 alteration.

Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare recently described entity. Fourteen CNS HGNET-MN1 patients were identified using genome-wide methylation arrays/RT-PCR across seven institutions. All patients had surgery (gross total resection: 10; subtotal resection: four) as initial management followed by observation alone in three patients, followed by radiotherapy in eight patients (focal: five; craniospinal: two; CyberKnife: one) and systemic chemotherapy in three patients. Seven patients relapsed; five local and two metastatic, despite adjuvant radiotherapy, of which three died. Treatment of CNS HGNET-MN1 remains a major treatment challenge despite aggressive surgical resections and upfront radiotherapy, warranting new approaches to this rare malignancy.