Background
IAEA-sponsored Phase III, open-label, multicenter RCT. 98 patients with newly diagnosed GBM, age ≥65 years, KPS ≤50 or age ≥70 with any KPS — a frail/very elderly population. Conducted across multiple countries. Compared two hypofractionated regimens: 40 Gy/15fr vs an even shorter 25 Gy/5fr schedule. The rationale was to identify the shortest effective RT course for patients unable to tolerate standard 6-week treatment.
Interventions and follow up
Arm A: Shorter hypofractionated radiotherapy — 25 Gy in 5 daily fractions over 1 week
Arm B: Standard hypofractionated radiotherapy — 40 Gy in 15 fractions over 3 week
Primary endpoint: Overall survival
mFollow up: Median not specified; final analysi
Arm B: Standard hypofractionated radiotherapy — 40 Gy in 15 fractions over 3 week
Primary endpoint: Overall survival
mFollow up: Median not specified; final analysi
Results
OS: 7.9 months (25 Gy/5fr) vs 6.4 months (40 Gy/15fr) — equivalent, non-inferior
6-month OS: 57% vs 48%
KPS maintenance: Similar between arms
Treatment completion: Higher in 25 Gy arm (fewer missed fractions due to shorter course)
6-month OS: 57% vs 48%
KPS maintenance: Similar between arms
Treatment completion: Higher in 25 Gy arm (fewer missed fractions due to shorter course)
Adverse events
Main adverse events: Similar acute toxicity profile. No grade 4 toxicity reported. 25 Gy/5fr was well-tolerated and completed by most patients. Corticosteroid requirements similar.
Conclusions
The ultra-short 25 Gy/5fr regimen was non-inferior to 40 Gy/15fr in elderly/frail GBM patients, with similar OS and toxicity profile. The 1-week schedule is logistically advantageous for debilitated patients and resource-limited settings.
Key Limitations
Key Limitations: Small sample size (N=98) — limited power for subgroup analyses. No TMZ arm or comparison with standard 60 Gy — not designed to show superiority over the Stupp backbone. MGMT status not prospectively evaluated. The very elderly/frail population limits generalizability to fit younger elderly GBM. No quality of life instruments reported. IAEA sponsor may limit applicability to resource-rich settings where options are broader.
Clinical Context
This trial established 25 Gy/5fr as an acceptable alternative to 40 Gy/15fr for the oldest, most frail GBM patients — particularly relevant in palliative intent care and low-resource settings. Current WHO and NCCN guidelines accept 25 Gy/5fr as an option for patients with very poor performance status. For fit elderly patients ≥65yr, EORTC 26062 (Perry 2017) data support 40 Gy/15fr + TMZ as the standard. The 25 Gy/5fr regimen is most appropriate when 3-week RT is burdensome.
References
References: Roa W et al, Mol Clin Oncol 2015 (IAEA Trial)