CTNI-20. NEOADJUVANT RADIOTHERAPY IN GLIOBLASTOMA IDH-WILDTYPE: INTERIM RESULTS FROM THE POBIG (PREOPERATIVE BRAIN IRRADIATION IN GLIOBLASTOMA) STUDY

Abstract Glioblastoma IDH-wildtype is a highly infiltrative and aggressive brain tumour, making complete surgical resection unachievable. Preclinical evidence suggests that surgical manipulation may contribute to tumour recurrence by stimulating the proliferative and migratory potential of the tumour. Neoadjuvant approaches, treating the tumour in its undisturbed state, remain largely unexplored in glioblastoma. The POBIG trial (NCT03582514) was initiated to assess the feasibility, safety, and preliminary efficacy of preoperative radiotherapy in glioblastoma. POBIG enrols patients using MRI-based diagnostic criteria, eliminating the need for pre-treatment biopsy. The study follows an initial dose-escalation (8–14Gy) followed by an irradiated volume-escalation (<30cc, 30–60cc, >60cc). A single high-dose radiation fraction is delivered preoperatively, followed by standard postoperative chemoradiotherapy (60Gy in 30 fractions with concurrent temozolomide). Following each cohort of three patients, a three-month observation period is used to monitor for adverse effects before escalating dose or volume. In initial cohorts, only partial tumour irradiation was done to enable comparison between irradiated and non-irradiated tissue for molecular and pathological analyses. Overall survival (OS) is measured from the time of preoperative treatment, with enrolment of the planned 18 patients expected to be completed by 2025Q3. This report presents interim outcomes from the first ten patients enrolled between 2022 and 2024. Nine had histologically confirmed glioblastoma; one was diagnosed with pilocytic astrocytoma and excluded. The median OS was 20.4 months, and six patients were alive at the time of analysis. No surgical complications were observed following preoperative radiotherapy. Seven patients (78%) developed new contrast-enhancing abnormalities, with a median onset of 5.9 months. Three underwent reoperation for suspected progression; pathology revealed reactive gliosis and inflammation without unequivocal recurrence. Four patients experienced true progression—three outside the POBIG field but within the standard postoperative field, and one outside all treated areas. These findings suggest that preoperative radiotherapy is feasible, not associated with increased surgical complications, and may reduce local recurrence. Continued investigation through POBIG is warranted.