A Phase 1/2 Trial of Reirradiation for Diffuse Intrinsic Pontine Glioma

Abstract

To identify an optimal dose for reirradiation (reRT) of diffuse intrinsic pontine glioma. ReRT dose levels were selected using an adaptive utility-based dose-finding method. The coprimary endpoints were toxicity (mild, moderate, high, or severe) and efficacy, evaluated 1month after reRT. Efficacy was defined as improvements in imaging, clinical status, and quality of life. Secondary endpoints were progression-free and overall survival. Utility of each dose level was calculated based on a combined toxicity/efficacy score, ranging from 0 for (severe toxicity, no efficacy) to 100 for (mild toxicity, all 3 efficacy improvements). Twelve patients completed reRT at 3 dose levels: 24Gy in 12 fractions (6 patients), 26.4Gy in 12 fractions (4 patients), and 30.8Gy in 14 fractions (2 patients). One patient treated at dose level 3 developed a grade 3 acute toxicity. Five of the 6 patients receiving 24Gy demonstrated improvement in 2 of 3 efficacy domains, and the sixth demonstrated improvement in all efficacy domains. Of 4 patients receiving 26.4Gy, 1 demonstrated no improvement, and 1 patient each demonstrated improvement in 1, 2, and 3 efficacy domains. Of 2 patients receiving 30.8Gy, 1 demonstrated improvement in 3 efficacy domains, and 1 did not complete the quality of life and was not assessed. Mean utilities were 88 for dose level 1, 76 for dose level 2, and 25 for dose level 3. For all patients, the median overall survival was 19.5months from initial diagnosis (95% confidence interval, 15.6-21.1months), and the median progression-free survival was 4.5months from the start of reRT (95% confidence interval, 2.7-6.2months). ReRT can safely be delivered for progressive diffuse intrinsic pontine glioma. Clinical improvement was seen in almost all patients. Utility analysis suggests that a regimen of 24Gy in 12 fractions is preferred.