What are the current radiotherapy guidelines for treating brain‑stem glioma, including recommended dose, fractionation, technique, and use of concurrent temozolomide for high‑grade lesions?

Brainstem Glioma Radiotherapy Guidelines

For diffuse intrinsic pontine glioma (DIPG) and brainstem gliomas, conventional fractionated radiotherapy remains the standard treatment, with a recommended dose of 54-60 Gy delivered in 1.8-2.0 Gy fractions over 6 weeks, targeting the tumor with a margin while carefully limiting dose to critical brainstem structures. 1

Dose and Fractionation

Standard Approach:

• Deliver 54-59.4 Gy in conventional fractionation (1.8-2.0 Gy per fraction) over 6 weeks 2
• This represents the established standard based on decades of clinical experience, though survival outcomes remain poor with median survival of 8-9.5 months 1

Alternative Fractionation Schemes:

• Hyperfractionated radiotherapy (70.2 Gy in 1.17 Gy twice-daily fractions) shows no survival advantage over conventional fractionation (HR 1.07,95% CI 0.75-1.53) and should not be routinely used 1
• Hypofractionated radiotherapy (39 Gy in 13 fractions over 2.6 weeks) may be considered for patients where reducing treatment burden is prioritized, as it shows similar survival outcomes (HR 1.03,95% CI 0.53-2.01) with median OS of 7.8 months versus 9.5 months for conventional fractionation 1

Target Volume and Technique

• Use focal, conformal radiotherapy targeting the visible tumor on MRI rather than whole-brain radiation 3
• Employ three-dimensional conformal RT (3DCRT) or intensity-modulated RT (IMRT) to maximize dose differential between tumor and normal tissue 3
• Keep dose to critical structures (brainstem, optic chiasm/nerves) within acceptable limits, though specific constraints are not defined in the available evidence 4
• Modern techniques including IMRT enable better normal tissue sparing without improving survival, but may reduce treatment-related toxicity 3

Concurrent Temozolomide

The evidence does NOT support routine use of concurrent temozolomide with radiotherapy for brainstem gliomas:

• In pediatric DIPG, concurrent temozolomide (75 mg/m² daily during RT) followed by adjuvant temozolomide does not improve the poor prognosis 5
• A study of 15 children showed median time to progression of only 7.15 months with no complete responses, and the regimen failed to extend survival beyond historical controls 5
• Another pediatric series showed median survival of 20 months with concurrent temozolomide, but this included patients with potentially lower-grade tumors and small sample size limits interpretation 2

Important distinction: The guidelines for supratentorial glioblastoma (which recommend concurrent and adjuvant temozolomide) 4 do NOT apply to brainstem gliomas, as these are biologically and clinically distinct entities with different treatment responses.

Timing of Treatment

• Initiate radiotherapy as soon as safely permissible after diagnosis, typically 3-6 weeks after any surgical intervention 4
• For brainstem gliomas, biopsy is often not performed due to location, and treatment proceeds based on characteristic MRI findings 2, 6

Recurrent Disease

For adults with recurrent "low-grade" diffuse brainstem glioma after initial radiotherapy:

• Consider temozolomide at 150-200 mg/m² for 5 days every 28 days 6
• This approach showed clinical improvement in 60% of adult patients with median PFS of 9.5 months after TMZ 6
• Grade 3 thrombocytopenia occurred in 26% of cases, requiring monitoring 6
• Reirradiation may be considered in select cases with good performance status, though no phase III data exist to guide optimal dose or volume 4

Critical Caveats

• Brainstem gliomas have universally poor prognosis despite all treatments, with median survival under 12 months for most patients 1, 5
• Tumor volume matters: Patients with primary disease volume <40cc show better median survival (26 months) compared to >40cc (13.5 months) 2
• The primary goal of modern radiotherapy techniques is reducing toxicity rather than improving survival, as no dose escalation or altered fractionation has demonstrated survival benefit 3
• Quality of life considerations favor hypofractionated approaches when appropriate, to decrease treatment burden during limited remaining lifespan 1