CTNI-44. HYPOFRACTIONATED CHEMORADIATION FOR NEWLY DIAGNOSED GLIOBLASTOMA: A MULTICENTER RANDOMIZED CLINICAL TRIAL IN THE NETHERLANDS

Abstract INTRODUCTION In the vulnerable population of patients with glioblastoma (GBM), there is a strong need for efficient treatment, while maintaining health-related quality of life (HRQoL). Since 2005, the standard of care involves radiotherapy of 2Gy in 30 fractions, with temozolomide (PMID: 15758009). A prior single arm phase II study (n=40) suggests that extreme hypofractionation (6Gyx6) may offer comparable survival with reduced treatment time and costs (PMID: 25107913). METHODS A phase III randomized clinical trial was performed to evaluate non-inferiority of a hypofractionated treatment schedule (6Gy times 6, in 2 weeks) versus standard of care (2Gy times 30), in newly diagnosed GBM patients with Karnofsky performance status ≥70. All patients received concurrent treatment and adjuvant temozolomide for six months. The primary endpoint was Overall Survival (OS); secondary outcomes included progression-free survival (PFS), toxicity and HRQoL. RESULTS Enrollment was halted early, due to poor accrual (n=129 of planned 474). Patients were randomized in the experimental arm (n=65) or standard arm (n=64). At a median follow-up duration of 24 months, median OS was shorter in the experimental arm (13.0 months, 95% confidence interval [CI] 10.2-15.8) versus the standard arm (median OS not reached yet, p=0.002). Cox regression identified treatment arm (Hazard Ratio [HR] 2.19, p=0.001) and age (HR 1.04, p = 0.008) as independent predictors of poor survival. Median PFS was also reduced in the experimental arm (9 versus 10 months, p=0.048). Clinical toxicity analysis showed a significantly higher rate of reported radionecrosis in the experimental arm (58.5% vs 23.1%, p<0.001). Longitudinal HRQoL data is reported separately. CONCLUSION In the treatment of newly diagnosed glioblastoma with temozolomide-based chemoradiation, non-inferiority of hypofractionation using 6Gy times 6, compared to the conventional 2Gy times 30 regimen, could not be demonstrated. The hypofractionation schedule is associated with inferior PFS and OS, along with increased reports of radionecrosis.