Glioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.

Background: Glioblastomas (GBMs) in eloquent areas, particularly within the motor system, represent a significant surgical challenge due to the risk of postoperative neurological deficits. This study evaluates the effectiveness of a structured preoperative protocol, including nTMS-guided motor mapping, to optimize surgical outcomes and minimize neurological deficits, with a particular focus on the timing of adjuvant oncological therapy initiation. Methods: A retrospective analysis was conducted on 44 GBM patients, divided into two groups: 11 with motor area lesions (group A) and 33 with non-eloquent lesions (group B). All patients underwent a standardized preoperative protocol. Surgical outcomes (EORs), neurological function (MRC score and KPS index), time to oncological therapy initiation and survival (OS and PFS) were compared between groups. Results: Both groups achieved high rates of GTR without significant differences in EOR (72.7% group A vs. 78.8% group B). Although group A exhibited a higher incidence of postoperative motor deficits, motor function at three-month follow-up was similar between groups. Time to initiation of oncological therapy did not differ between groups (40.6 days group A vs. 41.9 days group B, p = 0.719), highlighting that preservation of motor function helped minimize delays in starting oncological therapy. No significant differences were found in survival outcomes. Conclusions: A structured preoperative protocol incorporating nTMS motor mapping allows for safe and aggressive resection of motor-area GBMs. This approach effectively mitigates the risk of delays in initiating adjuvant oncological therapy, optimizing the patient prognosis. Further studies are needed to explore the long-term benefits of this protocol in both functional and oncological outcomes.