Single Institution Experience with Re-Irradiation of Diffuse Intrinsic Pontine Gliomas

Abstract

Diffuse intrinsic pontine glioma (DIPG) is the leading cause of death from CNS cancers in children. Radiotherapy is the standard initial treatment and re-irradiation (rRT) for symptomatic relief is an option at disease progression. Due to a low disease incidence, published data on treatment details and outcomes are limited. We have previously reported outcomes on a cohort of patients who received re-irradiation to the brainstem, however, not all tumors in that study were found to be gliomas. The objective of this study was to review and report our institutional experience with re-irradiation of DIPG. We identified a cohort of pediatric patients with biopsy-proven DIPG with clinical disease progression after initial radiotherapy who received a second course of radiotherapy at our institution between 2014 and 2018. We reviewed patient characteristics, treatment details, postmortem pathology, and laboratory results to identify possible correlates with clinical outcomes (post-rRT survival). To quantify these relationships, we performed a simple linear regression to generate a Pearson correlation coefficient (r). Between January 2014 and July 2018 we identified five patients with progressive DIPG who received re-irradiation. The average time from initial treatment to re-irradiation was 10 months. Three of the five patients received systemic therapy during re-irradiation (erlotinib plus bevacizumab). Mean initial RT dose was 55 Gy. Re-irradiation doses ranged between 20 and 24 Gy in 2.0 Gy fractions. Median survival from re-irradiation to death was 116 days. Percent-increase in LDH during the course of rRT was strongly negatively correlated with survival (r = -0.99), whereas length of time between RT and rRT was positively correlated with survival (r = +0.96). Cumulative dose in EQD2 (α/β = 2) did not correlate strongly with survival. In patients with available postmortem neuropathology, common findings were Wallerian degeneration and necrosis. Re-irradiation is safe and feasible for patients with DIPG with symptomatic disease progression following initial radiotherapy treatment. LDH kinetics during the course of re-irradiation correlated negatively with survival while time between radiation courses correlated positively with survival. However, a possible mechanistic link between such variables and survival is not clear and it is more likely that these factors are independently related to disease activity.Abstract 2431; TablePatientAge (yrs)Dose RT (1.8 Gy/fx)Dose rRT (2.0 Gy/fx)Cumulative EQD2 (Gy)Survival from last RT (days)Concurrent chemoPostmortem pathologyLDH rRT start (u/L)LDH rRT end (u/L)ΔLDH (%)11059.42480.479YFocal necrosis, Wallerian degeneration67795340.82357.62478.778YDiffuse necrosis, Wallerian degeneration36751339.83450.42067.9120NN/A478588234559.42480.4116YFocal necrosis, Wallerian degeneration34143026.15350.42471.9160NN/A24327312.3 Open table in a new tab