Ultra-hypofractionated versus conventional chemoradiation for newly diagnosed glioblastoma: Survival and toxicity results of a multicenter randomized trial
In brief
Ultra-hypofractionated chemoradiation cuts glioblastoma survival by eight months
In a randomized trial of 135 patients, a 2-week, 6-session radiation schedule with temozolomide yielded a median overall survival of 13 months versus 21 months with the conventional 6-week regimen. The shorter regimen also more than doubled rates of radiation necrosis, offering no survival benefit and raising safety concerns.
- Journal
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Q1)
- Published
- 8 August 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Anouk M de Jong, Arthur T J van der Boog, Gerda Wester, Daniëlle B P Eekers, Tom C G Budiharto, Tom Rozema, et al.
- PMID
- 42570798
- DOI
- 10.1016/j.radonc.2026.111726
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (paper of the day, 13 August 2026): Phase III RCT, ultra‑hypofractionated glioblastoma chemoradiation
Abstract
PURPOSE: In glioblastoma, standard first-line chemoradiation since the 2005 EORTC/NCIC trial is 30x2Gy with concurrent and adjuvant temozolomide. A phase II study suggested ultra-hypofractionation (6x6Gy) may offer comparable survival, with reduced treatment time and costs, potentially improving health-related quality of life (HRQoL). This phase III randomized trial (Netherlands Trial Registry, NL72953.041.20) evaluated non-inferiority of ultra-hypofractionated temozolomide chemoradiation in glioblastoma patients. PATIENTS AND METHODS: Adults with newly diagnosed glioblastoma and a Karnofsky performance status ≥70 were randomized (1:1) to ultra-hypofractionated (6x6Gy in 2 weeks) or standard (30x2Gy in 6 weeks) radiotherapy, both with concurrent and 6 cycles of adjuvant temozolomide. The primary endpoint was 2-year overall survival (OS); the non-inferiority margin was a hazard ratio of 1.2. Secondary outcomes included progression-free survival (PFS) and toxicity. RESULTS: Enrollment stopped early, due to slow accrual (n=135/474 planned, 67 experimental, 68 standard). Median OS was shorter in the experimental arm: 13.0 months (95% CI 10.3-15.7) versus 21.0 months (95% CI not estimable). In a time-dependent analysis, survival was similar in the first 6 months (HR 0.99, 95% CI 0.39-2.50), but mortality was higher thereafter (HR 2.54, 95% CI 1.57-4.09, p < 0.001). Radiation necrosis or pseudoprogression was more frequent after ultra-hypofractionation (47.8% vs 16.2%; HR 5.20, 95% CI 2.56-10.58), with increased dexamethasone use at 6-12 months. No grade 4-5 toxicities were observed. CONCLUSION: Non-inferiority of the 6x6 Gy chemoradiation regimen could not be demonstrated. This ultra-hypofractionated regimen was associated with inferior survival and increased radiation necrosis, and therefore should not replace standard chemoradiation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.