INNV-36. Personalised multimodal management of multifocal WHO grade 4 IDH-wildtype glioblastoma: a case study demonstrating prolonged survival through surgery, chemotherapy, radiotherapy, and genomic profiling

Abstract Multifocal glioblastoma multiforme (GBM) is associated with a poor prognosis, with a median survival of approximately six months. We present the case of a 51-year-old female diagnosed with multifocal WHO Grade 4 IDH-wildtype GBM, involving bilateral frontal infiltrating tumours with extension into the left centrum semiovale and corpus callosum, and exhibiting MGMT promoter methylation (25–50%). Management employed an individualised, multimodal approach incorporating surgery, chemotherapy, radiotherapy, and genomic profiling. A stereotactic burr hole biopsy on 15/09/2024 confirmed the diagnosis, undertaken due to eloquent location, fixed neurological deficit despite dexamethasone, and multifocal disease. Genomic profiling identified pathogenic mutations in TP53, RB1, KMT2D, TERT, BCOR, and PTEN, along with variants of uncertain significance in FGFR3 and PIK3CG. Tumour mutation burden was low, microsatellite instability was not detected, PD-L1 was negative, and mismatch repair proficient. Temozolomide chemotherapy was initiated on 23/09/2024. Hypofractionated radiotherapy (40.05 Gy in 15 fractions) commenced on 14/10/2024, targeting the dominant enhancing, biopsied left frontal lesion, concurrent with the second chemotherapy cycle. Following treatment initiation, the patient’s Karnofsky Performance Status improved from 70% to 90–100%, facilitating independent ambulation and enhanced quality of life. After the seventh cycle of temozolomide, oligoprogression was observed with enlargement of a right frontal lesion. The patient underwent craniotomy for resection on 04/05/2025, with plans for further radiotherapy and continued chemotherapy targeting this site. This case underscores that, despite the typically poor prognosis of multifocal GBM, a personalised, stepwise multimodal approach—guided by molecular insights and functional status—can yield meaningful clinical benefit and extended survival. At the time of reporting, the patient maintains excellent performance status and quality of life, emphasising the value of adaptive, individualised care in this aggressive disease.