Background
Phase III, prospective multicenter RCT. 100 patients with newly diagnosed GBM, age ≥60 years. First randomized trial comparing standard 60-Gy RT with a shorter-course 40-Gy regimen specifically in older GBM patients. Primary hypothesis: abbreviated RT is non-inferior to standard RT in overall survival.
Interventions and follow up
Arm A: Standard radiotherapy — 60 Gy in 30 fractions over 6 week
Arm B: Abbreviated radiotherapy — 40 Gy in 15 fractions over 3 week
Primary endpoint: Overall survival
mFollow up: All 100 patients had died at analysi
Arm B: Abbreviated radiotherapy — 40 Gy in 15 fractions over 3 week
Primary endpoint: Overall survival
mFollow up: All 100 patients had died at analysi
Results
OS: 5.6 months (40 Gy) vs 5.1 months (60 Gy), P=.57 — equivalent
6-month survival: 41.7% vs 44.7% — equivalent
Post-treatment corticosteroid increase: 23% (40 Gy) vs 49% (60 Gy), P=.02
6-month survival: 41.7% vs 44.7% — equivalent
Post-treatment corticosteroid increase: 23% (40 Gy) vs 49% (60 Gy), P=.02
Adverse events
Main adverse events: No major differences in KPS between arms. Abbreviated RT was associated with significantly less corticosteroid requirement post-treatment (23% vs 49% requiring increase, P=.02). Low FACT-Br QoL completion rates (45%) precluded formal QoL comparison. No radiation necrosis reported.
Conclusions
Abbreviated 40 Gy/15fr and standard 60 Gy/30fr had equivalent overall survival in elderly GBM patients (≥60 years), with less corticosteroid requirement in the short-course arm. Established 40 Gy/15fr as a reasonable alternative to standard RT in older patients.
Key Limitations
Key Limitations: Small sample (N=100) — powered for equivalence with wide margins; formal non-inferiority analysis not pre-planned. No temozolomide arm — performed before the Stupp 2005 trial. Only 45% FACT-Br completion limits QoL conclusions. The 40 Gy/15fr arm was not compared to the even shorter Roa 2015 regimen (25 Gy/5fr) in this trial.
Clinical Context
This trial established the proof of concept that hypofractionated RT is non-inferior to standard RT for elderly GBM. The Nordic trial (Malmstrom 2012) later showed that TMZ monotherapy was superior to standard RT in elderly patients, especially those >70 years. EORTC 26062 (Perry 2017) subsequently showed that 40 Gy/15fr + TMZ is superior to 40 Gy/15fr alone. The Roa 2004 regimen (40 Gy/15fr) is now widely used as the RT backbone for elderly GBM in combination with TMZ.
References
References: Roa W et al, J Clin Oncol 2004