3 MR-Linac on-Line Weekly Adaptive Radiotherapy for High Grade Glioma (Hgg): Results From the United Single Arm Phase Ii Trial

To assess the safety of weekly on-line MR-Linac (MRL) adaptive RT with concurrent temozolomide (chemoRT), with a reduced 5 mm clinical target volume (CTV) margin, for patients with GBM. Methods: Patients with newly diagnosed GBM planned for chemoRT with either 60 Gy/30 # (long course) or 40 Gy/15 # (short course) were eligible. A reduced 5 mm CTV was applied to the gross tumor/surgical cavity. All patients were treated using a 1.5T integrated MRL with contrast-enhanced imaging every 5th fraction and daily plan adaptation. The primary endpoint was the risk of a marginal failure (MF) at the time of recurrence powered for non-inferiority compared historical rates of MF of 11%. Secondary endpoints included progression-free survival (PFS) and overall survival (OS) according to treatment schedule (long versus short course). Results: Adaptive RT was delivered to 98 patients (59 long course and 39 short course). All tumors were IDH-wt and 53% were MGMT methylated. MF events were observed in 4/98 (4%) patients, establishing non-inferiority (p<0.001); the most common pattern of failure was central (52%). Median PFS / OS was 11.6 / 18.5 mo (long course), and 6.8 / 10.6 mo (short course). Conclusion: This is the first trial evaluating on-line MRL adaptive chemoRT for GBM with a limited CTV. Safety and feasibility was demonstrated with a low risk of MF (4%) without compromising PFS or OS. Further trials are required to test whether the reduction in radiated normal brain tissue using this approach results in neurocognitive and quality of life benefits.