DMG-31. Radiation-induced diffuse intrinsic pontine glioma/diffuse midline glioma in pediatric patients with Craniopharyngioma - A case series

Radiation-induced second malignancies are a recognized complication in a subset of patients undergoing cranial radiation therapy (RT). The standard approach in Craniopharyngioma (CP) is complete surgical resection or debulking surgery followed by adjuvant RT. However, radiation therapy is associated with long-term complications like radiation-induced malignant gliomas (RIMGs). This series presents three cases of radiation-induced (RI) diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG) developed after radiation therapy for pediatric CP patients from three different continents after taking ethical approvals individually. These cases are reported from Pakistan, Switzerland, and the United States. The ages at diagnosis with CP were 6 years, 9.25 years, and 6 years respectively with a female-to-male ratio of 2:1. They all underwent subtotal resection followed by RT with photons (n = 2) and protons (n = 1) at a median dose of 54 Gy (30 fractions). DIPG/DMG was diagnosed after a median duration of 8 years after initial RT (Range 4.5- 9.75 years). Two DIPG/DMG cases were diagnosed during surveillance and the one from Pakistan was diagnosed after the development of symptoms of a brainstem lesion. Biopsy was done in two of the cases (Switzerland, and the US). One showed diffuse astrocytoma with MYCN, PDGFRA, and MDM2 amplification and a novel fusion (RBD7-FLI1) while the other case had an inconclusive histopathology. Re-irradiation was done in two cases (54Gy/30Fr and 30Gy/10Fr) while the third case refused RT and received Bevacizumab. All three cases succumbed to RI-DIPG with a median survival of 7.5 months (Range 4.0 – 58 months). It is concluded that this is the first case series of radiation-induced DIPG/DMG following RT for pediatric CP. Although radiation-induced DIPG/DMG is rare in this population, our findings underscore the importance of heightened clinical awareness of this severe complication. The outcomes are uniformly poor reflecting the grave prognosis of this condition, seemingly independent of treatment modalities and resources.