KEY POINTS
- The report combines two institutional cases with a systematic PubMed review identifying 10 previously published patients, producing a total global cohort of 12 patients who received at least three radiation courses for DIPG or H3K27-altered diffuse midline glioma.
- Across the combined experience, median age was 6 years, median time to first progression 11 months, and median overall survival from diagnosis 27 months. Most patients received 54 Gy upfront, approximately 30.6 Gy at first reirradiation and approximately 20 Gy at the next course.
- The first institutional patient, a 34-year-old woman with H3K27-altered pontomedullary disease, received 54 Gy/30, then 25 Gy/10, 15 Gy/6, and finally 10 Gy/4. Each of the first two reirradiation courses produced symptomatic improvement; the fourth total RT course provided some symptom relief but was followed by declining quality of life. She survived 33 months from diagnosis.
- The second institutional case was a 5-year-old girl treated with 54 Gy/30, followed 13.5 months later by 30 Gy/10 and then 15 Gy/6 another 6.5 months later. The second reirradiation produced marked improvement in walking, energy and appetite and radiographic tumor shrinkage; overall survival was 34.5 months.
- Published experience suggests that symptomatic responses after additional low-dose reirradiation are possible, but patient selection is extreme. The median interval between first and second reirradiation courses was approximately 6.3 months, and the reported patients generally had unusually long initial responses compared with the typical DIPG natural history.
- Safety remains poorly defined. Two previously published patients developed radionecrosis after their second reirradiation, and the adult institutional patient developed symptoms after her final course for which tumor progression was favored but radionecrosis could not be excluded.
- There are no consensus dose recommendations for repeated DIPG reirradiation. Most first reirradiation regimens in the literature fall around 20–36 Gy, while subsequent courses have generally used progressively lower doses; the authors emphasize that a third course should be considered only individually rather than routinely.
CLINICAL TAKEAWAY
A third radiation course should not automatically be ruled out in exceptionally selected patients with recurrent DIPG who previously experienced durable response and symptomatic benefit from RT. The evidence is nevertheless based on only 12 cases, with major selection bias and uncertain radionecrosis risk, so this remains individualized palliative decision-making rather than a treatment standard.