Influence of FLAIR inclusion on patterns-of-failure and outcomes in glioblastoma: results from the UNITED prospective adaptive radiotherapy trial.

Abstract

Inclusion of the peritumoral FLAIR-hyperintense-region (FHR) within the clinical target volume (CTV) for glioblastoma (GBM) varies across guidelines. Using data from a prospective phase 2 trial employing small-margin MR-guided adaptive radiotherapy (RT), we evaluated whether inclusion of FHR influences the pattern-of-failure (POF) and clinical outcomes. Patients with newly diagnosed GBM underwent chemoRT with weekly online-adaptive planning on an MR-Linac (NCT04726397). The gross tumor volume (GTV) included the resection cavity and residual enhancing tumor. The CTV was defined as GTV + 5 mm, with inclusion of FHR beyond 5 mm at the clinician's discretion. For this post hoc analysis, three contour categories were identified: no FHR beyond 5 mm (NF), FHR present but not included (FNI), and FHR included (FI). At radiographic progression, the recurrent GTV (rGTV) was delineated on co-registered MRIs to quantify overlap with the CTV and summed RT dose. rGTV coverage, dose/volume histogram metrics, progression-free survival (PFS), and overall survival (OS) were compared among groups. Among 98 patients, 24 were NF, 27 FNI, and 47 FI. Recurrences (n = 69) were predominantly central (65-72%) with no difference between groups (p = 0.717). Median rGTV coverage within the CTV was 97.9% and was comparable across strategies (p = 0.105), as was estimated rGTV dose. Median PFS and OS for the NF, FNI, and FI cohorts were 10.5, 8.0, and 8.6 months (p = 0.279) and 16.9, 15.8, and 13.4 months (p = 0.389), respectively. Multivariable analysis revealed no significant differences between contouring strategies on outcomes. Within a small-margin MR-guided adaptive RT paradigm, omission of FHR did not negatively influence the POF or survival outcomes.