Early target volume dynamics during MR-guided radiotherapy for glioblastoma: first results from the prospective MARGA-I trial

Serial MRI during radiotherapy may enable early response assessment and guide adaptive treatment strategies; however, data on intratreatment volumetric changes remain limited. We herein report results of the MARGA-I-study, investigating target volume changes during MR-linac-based radio-(chemo-)therapy. In this prospective single-center-study, 25 patients with glioblastoma were treated on a 0.35-T-MR-linac. TrueFISP and T2-FLAIR images were acquired before treatment and every fifth fraction. TrueFISP-based extended resection cavity (cavity/tumor residue) and FLAIR-hyperintense volumes were contoured and analyzed longitudinally. Volume changes were stratified among early (SIM-f5) and late (f5-last fraction) phase and changes >±10% were deemed major. The exceedance of the volumes over the CTV and 95% isodose line was evaluated. Extended-resection-cavity- and FLAIR-contours derived from MR-linac imaging showed correspondence with those from diagnostic MRI (Pearson r > 0.96). In the extended resection cavity, 59%/27%/14% of analyzed patients showed major increase/major decrease/minor changes respectively. In FLAIR contours, the prevalences were 79%/0%/21% respectively. Differences between early and late volume changes were not statistically significant. The FLAIR contours exceeded CTV >1cc in 74% of patients, while the extended resection cavity exceeded the CTV and 95% isodose line >1cc in 27% and 18% respectively. No clinical or molecular parameter significantly predicted volumetric trajectories. Non-contrast MR-linac imaging reliably captures glioblastoma target volume dynamics during treatment. Volumetric changes are heterogeneous across patients and major changes can occur both early and late, underscoring the potential for serial imaging. Our data provide a rationale for further investigation of the clinical significance of these changes and their potential utility for individualized adaptive radiotherapy strategies.