KEY POINTS
- This international retrospective study included 167 children younger than 18 years with diffuse midline glioma treated across centres in Toronto, Birmingham, and Nottingham between 2010 and 2024. All had completed initial radiotherapy and subsequently developed radiological progression.
- Initial treatment was predominantly 54 Gy in 30 fractions, used in 144 patients (86.2%). At progression, 54 children (32.3%) received re-irradiation, while 113 received no second radiation course.
- Median overall survival from progression was 0.59 years with re-irradiation versus 0.21 years without it (p < 0.0001), corresponding to approximately 7.1 versus 2.5 months. Six-month survival was 68% versus 16%, and one-year survival was 19% versus 3%.
- Re-irradiation remained the strongest independent factor associated with survival after adjustment for clinical characteristics, with a 71% lower hazard of death (adjusted hazard ratio 0.29, 95% CI 0.20–0.42; p < 0.001).
- Patient selection was clearly present: children eventually receiving re-irradiation had a longer interval from initial radiotherapy to progression, 0.79 versus 0.52 years (p < 0.0001). The survival association nevertheless persisted in a secondary analysis restricted to children remaining progression-free for more than six months.
- Children re-irradiated at least one year after their first course had longer median survival after retreatment than those treated earlier: 0.81 versus 0.42 years (p = 0.0041). This likely reflects both treatment benefit and more favourable underlying tumour biology.
- The most common retreatment regimen was 30.6 Gy in 17 fractions, delivered to 24 patients (44.4%). Another 15 received 20 Gy in five or ten fractions, and 77.8% received focal-brain treatment. Doses of at least 30.6 Gy showed a nonsignificant trend toward longer survival (p = 0.086).
- Toxicity, symptom relief, performance status, and patient-reported quality of life were not systematically collected. The study also could not reliably distinguish radiation necrosis from progression, limiting conclusions about the optimal dose, fractionation, and net clinical benefit.
CLINICAL TAKEAWAY
Re-irradiation should be actively considered as a salvage option for children with recurrent diffuse midline glioma, particularly those with good performance status and a longer interval after initial treatment. The survival signal is substantial, but the evidence remains retrospective and does not establish the best regimen or quantify the trade-off between symptom benefit and cumulative brainstem toxicity.