Abstract Background Central nervous system Neuroblastoma, FOXR2-activated (CNS NB-FOXR2), is a recently defined supratentorial embryonal tumor entity. Emerging molecular data suggests more favorable outcomes compared with other embryonal tumors, however optimal therapy remains undefined. Current treatment protocols include radiation, however radiation-sparing approaches for young children with intensive chemotherapy and autologous stem cell transplant (aSCT) are often utilized given treatment-related toxicity. Objective To describe two cases of CNS NB-FOXR2 managed with therapy-limited approaches with varying clinical outcomes, highlighting the clinical heterogeneity in this population. Results Case 1: A 14-month-old male presented with acute neurologic decompensation and a large hemorrhagic left frontal mass, later confirmed to be CNS NB-FOXR2. He underwent multiple neurosurgical interventions, including eventual gross total resection, prior to starting induction chemotherapy per ACNS0334 (Regimen A). He developed severe CMV viremia and received two additional induction cycles with planned aSCT ultimately deferred. He has since been managed without further therapy; twenty-four months post-treatment, surveillance imaging continues to demonstrate remission of his tumor. Case 2: A 3-year-old male presented with emesis, lethargy and seizure-like activity. Imaging revealed a left frontotemporal supratentorial mass, and he underwent near total resection. Molecular profiling confirmed CNS NB-FOXR2. Given his age, he received five cycles of induction chemotherapy per ACNS0334 (Regimen A). The family elected to defer consolidation with aSCT or radiation due to toxicity concerns, so no further therapy was administered. Surveillance imaging at six months demonstrated radiographic recurrence within the resection cavity, despite absence of neurologic symptoms. Conclusion As demonstrated by these cases, there are challenges with balancing disease control with treatment-related toxicity, especially in young children. Larger cohorts of patients with more long-term data are therefore needed to better define risk-adapted strategies and identify patients in whom therapy-limited approaches may be appropriate. 1. Von Hoff, Katja, et al. “Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.” Neuro-oncology 23.9 (2021): 1597-1611. 2. Korshunov, Andrey, et al. “Molecular analysis of pediatric CNS-PNET revealed nosologic heterogeneity and potent diagnostic markers for CNS neuroblastoma with FOXR2-activation.” Acta neuropathologica communications 9 (2021): 1-12.
Cahaney et al. (Tue,) studied this question.