INTRAGO-II trial

Background

Open-label, multicentre, randomised phase 3 trial (18 centres, 7 countries). N=314 (298 full-analysis set) aged 18-80 with newly diagnosed supratentorial glioblastoma amenable to resection, KPS ≥60%. Tested adding kilovoltage intraoperative radiotherapy (IORT) to standard chemoradiotherapy.

Results

Interventions and follow up: Arm A: Surgery + IORT 30 Gy (kV) at resection, then standard EBRT 60 Gy with concurrent temozolomide 75 mg/m² and 6 adjuvant TMZ cycles (n=161)
Arm B: Surgery alone then standard chemoradiotherapy (Stupp) (n=137)
Primary endpoint: Progression-free survival (FAS, masked central review)
mFollow up: 17.2 months
Results: PFS: 11.0 mo vs 11.4 mo, HR 1.1 (95% CI 0.85–1.44), P=.47 (not significant)
Local recurrence (predominant failure): 72% vs 71%
OS: NR (not reported/immature)

Adverse events

Grade 3-4 seizure: 13% vs 7%
Radiation necrosis: 7% vs 2% (P=.06)
Serious adverse events: 65% vs 53% of patients

Conclusions

Intraoperative radiotherapy dose escalation added to standard care did not improve progression-free survival and increased radiation necrosis and seizures. The findings question further local dose intensification in resectable glioblastoma.

Key Limitations

Open-label design; PFS was the primary endpoint and OS is not yet reported (NR). Arm sizes were imbalanced (161 vs 137). Radiation necrosis in the IORT arm can mimic progression on imaging, potentially confounding a PFS endpoint even under masked review.

Clinical Context

The Stupp protocol (maximal safe resection, 60 Gy radiotherapy with concurrent/adjuvant temozolomide, with optional tumor-treating fields) remains standard of care. IORT is not standard practice; INTRAGO-II confirms no role for routine intraoperative dose escalation. No regulatory or guideline change.

References