In a phase III trial (INTRAGO-II) reported in The Lancet Oncology, Giordano et al found that the addition of intraoperative radiotherapy to surgery did not improve outcomes in patients with newly diagnosed glioblastoma.
Study Details
The open-label trial enrolled 298 patients (full-analysis set) from sites in Brazil, Canada, China, Germany, Spain, South Korea, and the United States. They were randomly assigned between December 2016 and June 2024 to receive additional kilovoltage intraoperative radiotherapy with 30 Gy (intraoperative radiotherapy group, n = 161) or surgery alone (standard-of-care [SOC] group, n =137). Postoperative treatment in both groups consisted of external-beam radiotherapy to 60 Gy with concurrent temozolomide at 75 mg/m², followed by six adjuvant cycles of temozolomide at 150 to 200 mg/m² on days 1 to 5 every 28 days. The primary endpoint was median progression-free survival in the full-analysis set, as confirmed by masked central review.
Key Findings
At a median follow-up of 17.2 months (interquartile range = 10.5–27.1 months), median progression-free survival was 11.0 months (95% confidence interval [CI] = 9.2–12.6 months) in the intraoperative radiotherapy group vs 11.4 months (95% CI = 9.7–13.9 months) in the SOC group (hazard ratio [HR] = 1.1, 95% CI = 0.85–1.44, P = .47). Local recurrence accounted for 72% of progression cases in the intraoperative radiotherapy group and 71% of cases in the SOC group.
Median overall survival was 17.7 months (95% CI = 15.5–21.1 months) in the intraoperative radiotherapy group vs 18.7 months (95% CI = 17.2–21.1 months) in the SOC group (HR = 1.2, 95% CI = 0.91–1.54, P =.20).
The most common grade 3 or 4 adverse events were seizure (13% in the intraoperative radiotherapy group vs 7% in the SOC group), radiation necrosis (7% vs 2%), thrombocytopenia (4% vs 8%), and muscle weakness (7% vs 14%). Serious adverse events considered at least possibly related to treatment occurred in 26% of the intraoperative radiotherapy group and 19% of the SOC group. Death considered at least possibly related to treatment occurred in 14 patients in the intraoperative radiotherapy group (due to CNS toxicity, myocardial infarction, and sepsis in two each, and cardiac arrest, fever, lung infection, fracture, postoperative hemorrhage, neoplasm, hematoma, and death–not otherwise specified in one each) and in 6 patients in the SOC group (due to lung infection in two and multiorgan failure, encephalitis, neoplasm, and cystitis in one each).
The investigators concluded: “Instant, spatially precise dose escalation with intraoperative radiotherapy added to standard of care did not improve outcomes, questioning the value of further local dose intensification in resectable glioblastoma.”
Frank A. Giordano, MD, of the Department of Radiation Oncology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by the Universities of Heidelberg and Bonn, Carl Zeiss Meditec, and Deutsche Forschungsgemeinschaft. For full disclosures of the study authors, visit sciencedirect.com.
