RADT-48. MAPPING ISOLATED LOCAL PROGRESSION IN NEWLY DIAGNOSED GLIOBLASTOMA TO INFORM ON A CLINICAL TARGET VOLUME MARGIN FOR A RADIATION BOOST TARGET

Abstract BACKGROUND Applied boost targets in radiation dose-escalation trials for newly diagnosed glioblastoma vary largely. This nationwide recurrence pattern study aims to map the distance of isolated local infiltration at first progression to inform on a potential radiation boost target. METHODS All adults newly-diagnosed with glioblastoma between 2015-2019 in Denmark, planned to start long-course chemoradiotherapy (59.4-60 Gy in 30-33 fractions) with a dedicated radiotherapy planning-MRI, were included (n=756). Patients with a confirmed IDH mutation were excluded (n=24). In total, 492 patients were available for analyses (treatment response not-evaluable n=82, no-radiographic progression n=62, CSF/meningeal/hematological dissemination n=28, technical error n=68). The gross tumor volume (GTV) and contrast-enhancing recurrence (following RANO-criteria) were automatically segmented on the respective MRIs using AI. Each segmentation was manually checked and adapted if needed. Imaging and radiotherapy dose distribution were rigidly co-registered. With respect to the 95% radiotherapy isodose of the clinical plans, recurrences were classified as central/in-field/marginal/distant in 414/22/21/35 patients, respectively. The GTV was expanded in 1mm steps to simulate clinical target volumes (CTV). The CTV expansion needed to cover 95% of the most distant recurrence volume was compared between those with isolated-local progression (i.e. contiguous with original site/resection margin), and those with non-local/combined progression by Mann-Whitney-U test. RESULTS In patients with isolated-local progression (n=352), a simulated 5/10/15mm CTV margin achieved recurrence coverage in 48/71/80% of the patients, respectively. Regarding non-local/combined progression patients (n=140), 5/10/15mm CTV margins achieved recurrence coverage in 1/6/15% of the patients, respectively (p<.001 vs. isolated local). In isolated-local progression patients with an MGMT methylated (n=136) vs. unmethylated tumor (n=206), a simulated 5/10/15mm CTV margin achieved recurrence coverage in 53/76/88% vs, 44/67/74% of patients, respectively (p=0.18). CONCLUSIONS Our cohort results can be used to select GTV-to-CTV margins for the radiation boost target in newly diagnosed glioblastoma patients.