Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy

Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20–40 Gy) in glioblastoma. INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P