When the cure becomes the curse: Radiation-induced glioma of the pons in children surviving craniopharyngioma

Abstract Background The standard of care for pediatric craniopharyngioma (CP) is either complete surgical resection or limited debulking surgery followed by adjuvant radiotherapy (RT). Recent data favor the latter approach. Methods We present a multi-center case series of three children with CP treated with subtotal surgery and adjuvant RT for CP who eventually developed radiation-induced glioma (RIG) of the pons. Results The median age at diagnosis of CP was 6 years. Photon RT was administered in two patients and proton RT in one, at a median dose of 54 Gy delivered in 30 fractions. Pontine glioma was first identified on imaging after a median interval of 8 years from initial RT (range 4.5 - 9.75 years), incidentally in two asymptomatic patients during routine surveillance, and associated with symptoms of brainstem involvement in one. A biopsy was performed in two patients. 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 (re-RT) (54 Gy/30 fractions and 30 Gy/10 fractions) was applied in two patients, and one patient received bevacizumab treatment. All three patients succumbed with a median survival of 7.5 months (range 4.0–58 months). Conclusions Radiation-induced glioma of the pons is a rare and serious complication occurring in patients previously treated by RT for childhood CP. This secondary tumor is uniformly associated with a dramatic course regardless of the treatment modalities and resources. This highlights the need for clinical vigilance and further research to prevent it.