Beyond Reirradiation: Third-Course Radiation Therapy in Recurrent Diffuse Intrinsic Pontine Glioma—Case Series and Literature Review

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive brainstem tumor with a poor prognosis, for which radiotherapy remains the only established treatment. Although reirradiation at first progression has been reported to provide symptomatic relief and survival benefit, the role of a third course of irradiation remains unclear. In this study, we report 3 cases of DIPG treated with a third course of radiotherapy at second recurrence and conduct a literature review to evaluate its clinical efficacy and safety. All 3 patients demonstrated radiologic disease stabilization following the third course of irradiation, with 1 patient showing partial neurological improvement. No permanent severe toxicity attributable to the third course of radiotherapy was observed; 2 patients transiently experienced consciousness disturbance, cerebral edema, and/or respiratory dysfunction. To further assess the clinical significance of this approach, we analyzed previously reported cases of DIPG treated with 3 courses of radiotherapy. Of the 21 identified rare cases, 13 with sufficient clinical data were included in the analysis. The median radiation doses for the first, second, and third courses were 54.0 (39.0 to 54.0), 20.0 (19.8 to 36.0), and 20.0 (12.0 to 24.0) Gy, respectively. Total median radiation doses of 3-course irradiation were 94.0 Gy (79.0 to 111.6). The median survival after the third irradiation was 5.5 (2 to 13) months, and the median overall survival was 20.5 (15 to 102) months, measured from the start of the first radiation. A radiologic response greater than stable disease was observed in 69.2% of cases, whereas clinical improvement or stabilization was noted in 93.7% of cases. Although further studies with larger cohorts are needed to clarify the efficacy and particularly the safety of this treatment due to the limited data on adverse events, 3 courses of irradiation may be a viable option for children with DIPG, with careful consideration of the risks and benefits.