Key Points Question In children with brain tumors, what is the referral rate to ophthalmology and what is the prevalence of visual sequelae and their association with tumor characteristics? Findings In this cohort study of 141 children with primary brain tumors, only 68 (48%) were referred for comprehensive eye examination. While only 15% of those referred had visual symptoms, more than 90% had a variety of visual impairments including both afferent and efferent diseases, with visual field defects being the most common impairment among patients without symptoms. Meaning Ophthalmologic evaluation is recommended for early diagnosis of visual sequelae in children with brain tumors to prevent permanent vision loss.

ES is a common complication in children after auto-HCT and short-course glucocorticoid therapy is an effective and well-tolerated treatment, even in those who did not completely fulfill diagnostic criteria.

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BACKGROUND: High-grade gliomas (HGG) with replication-repair deficiency (RRD) harbour high mutation burden (TMB) and are rapidly fatal following chemo-radiation approaches. Although hypermutation results in objective responses and prolonged survival in >30% of patients undergoing PD1-blockade, salvage following failure of PD1-inhibition remains a challenge. METHODS: We performed a real-world study of Ipilimumab (anti-CTLA4) in combination with Nivolumab/Pembrolizumab for patients failing single-agent PD1-inhibition. RESULTS: Among 68 consortium patients with relapsed HGG treated with single-agent PD1-inhibitors, progression was observed in 43 (63%). Ipilimumab was added to 20/43 (46.5%), 14 (32.5%) received best supportive care (BSC), and 9 (21%) received miscellaneous therapies. For patients receiving CTLA4/PD1-inhibition, median age at progression was 12.3-years (IQR: 9; 15.6). Time from anti-PD1 initiation to progression was 8-months (IQR: 3.8; 18.5). Germline predisposition was observed in all patients (CMMRD: 70%, Lynch: 25%, polymerase-proofreading deficiency: 5%). All HGG were hypermutant (median TMB: 182 mutations/Mb; IQR: 15.6; 369.4). Centralized radiology review revealed objective responses in 3/20 (15%, all ultra-hypermutant: 320, 496, 834 mutations/Mb), stable disease in 5 (25%), and 12 (60%) eventually progressed (iRANO). Following failure of PD1-blockade, estimated progression-free and overall survival at 18-months for patients receiving CTLA4/PD1-inhibition were 11% and 25%, respectively. Importantly, survival was superior to patients receiving BSC (median OS <1-month versus 12-months on CTLA4/PD1-inhibition; p<0.001). All patients receiving BSC died within 3.5-months, while 4/8 survivors were alive for >1-year on the anti-CTLA4/PD1combination (range:1-48 months). The combinational immunotherapy resulted in significant autoimmune toxicity in 11/20 (55%), warranting immunosuppressive therapy in all, and treatment abandonment in 6 patients. CONCLUSION: Combined CTLA4/PD1-blockade after failure of single-agent PD1-inhibition revealed objective responses and prolonged survival in an otherwise rapidly-fatal disease. This needs to be assessed in the context of significant autoimmunity, supporting the need for the current prospective trial (NCT04500548), and novel strategies to limit treatment-related toxicity.

Intradural extramedullary peripheral primitive neuroectodermal tumor (pPNET) with t(11;22) is a rare clinical finding in the pediatric population with few published cases in the literature. The authors report 3 cases of intradural primary pPNET and discuss the clinical presentation, treatment, and survival of the patients. Clinicians should be vigilant in considering pPNET in the differential diagnosis of extradural masses. The authors also compare the clinical course and outcome of therapy with primary PNET of the central nervous system and Ewing sarcoma family of tumors. In addition, this report highlights the risk for leptomeningeal dissemination at recurrence and discusses the importance of central nervous system-targeted therapy for durable disease control.

Acquired pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) are rare complications of immunosuppression in pediatric solid organ transplant patients. We report a 14-month-old female child who developed Coombs positive hemolytic anemia and reticulocytopenia while on tacrolimus after cardiac transplantation. She was successfully treated with rituximab after failing treatment with corticosteroids and intravenous immunoglobulins. Clinicians should consider PRCA differential diagnosis in a patient presenting with reticulocytopenia and hemolysis. In addition, the coexistence of PRCA with AIHA, and the response to therapy with rituximab, supports a common immune-mediated pathogenesis for both disorders.

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Background Ewing sarcoma (EWS) is a rare type of pediatric bone and soft tissue tumor that accounts for approximately 1% of all pediatric malignancies. It most commonly occurs in the long bones or axial skeleton, and rarely includes extraosseous sites or intracranial involvement. Reports of primary intracranial EWS are minimal. Pediatric intracranial EWS is even more rare with less than 15 cases reported. Case Description We describe the case of primary intracranial EWS in a 12 month old male. The patient’s initial MRI showed a large heterogeneous supratentorial cystic and solid mass centered in the right parietal region measuring 9.1cm x10.3cm x 7.6cm. No distant metastases were detected. The patient underwent surgical resection and pathology was consistent with a small round blue cell tumor. Further pathological evaluation revealed presence of EWSR1-FLI1 fusion and was negative for CD99, GFAP, synaptophysin, Olig2, desmin, and CAM5.2. Stains for INI1 and BRG1 were retained. The patient was treated with adjuvant chemotherapy and focal proton beam radiation (as per AEWS0031). Conclusion Primary intracranial Ewing Sarcoma is a rare pediatric brain tumor and, to our knowledge, this would be the youngest reported case to date. This case demonstrates the successful application of a sarcoma-based regimen to a primary intracranial EWS tumor with no evidence of residual tumor on MRI at 8 months into treatment. Future studies should be directed at understanding the biology of these rare tumors and optimizing treatment approaches.