Re-Irradiation for Diffuse Intrinsic Pontine Glioma with 3 Gy per Fraction

Abstract

Radiotherapy (RT) improves survival in pediatric diffuse intrinsic pontine glioma (DIPG). After recurrence, re-irradiation (re-RT) offers palliation of symptoms and extends life in patients after exhaustion of investigational options and clinical decline. Practice patterns vary in dose and fractionation for re-RT, with majority of reported cases treated with conventional fractionation. Given radiobiologic rationale for hypofractionation in glioblastoma, we hypothesized that treatment with 3 Gy per fraction is safe and effective for re-RT to the brainstem for DIPG. We identified patients at our institution, ages 1-25, treated with re-RT to the brainstem for DIPG from 2012-2022. Patient demographics, treatment details, and clinical outcomes were reviewed from the medical record. Analysis was completed in R 4.2.2 using Kaplan-Meier method with log-rank test for survival estimates and Fisher's exact test for categorical variables. A total of 22 patients received re-RT for DIPG. All patients had received 54-59.4 Gy with conventional fractionation at the time of diagnosis. Re-RT dose was initially 20-24 Gy in 2-Gy fractions (n = 6) and continued at 30-36 Gy in 3-Gy fractions (n = 14). Two patients did not complete re-RT due to continued clinical decline from disease progression after 1-2 fractions. Of the 20 that completed re-RT, 11 were female, median age was 5 years (3-14), median interval since initial RT was 8 months (3-20), 12 (60%) received concurrent bevacizumab, and OS from diagnosis was 18 months. Median OS from start of re-RT for patients treated with 3 Gy per fraction was 8.2 months and 13 (93%) clinically improved to taper pre-treatment steroid dose down (n = 9) or off (n = 4) within 2 months after re-RT. For those treated with 2 Gy per fraction, median OS from re-RT was 7.5 months and 3 (75%) improved to taper steroids down (n = 2) or off (n = 1). Overall, 2 patients were not on steroids, 2 were maintained at same steroid dose, and 0 required increase from pre-treatment steroid dose within 6 weeks after re-RT. There was no significant difference in OS from re-RT (p = 0.2) or steroid taper (p = 0.4) between fractionation groups. No patients developed radionecrosis of normal brain tissue. Patients receiving re-RT achieved extended survival comparable to published outcomes and majority experienced clinical improvement to allow steroid taper. While radionecrosis is a reported risk in prior published series, our experience demonstrates the safety and effectiveness of using 3 Gy per fraction to 30-36 Gy for meaningful palliation in this population.