Giorgio Fiore

Background: Intraoperative neurophysiological monitoring (IONM) facilitates safe glioma resection in eloquent regions. Its effect on survival in molecularly defined isocitrate dehydrogenase (IDH)-wildtype glioblastoma remains uncertain. We assessed the association between IONM-supported surgery and survival outcomes in this high-risk population and explored subgroups deriving the greatest benefit. Methods: We retrospectively analyzed 200 adults who underwent first-time resection for IDH-wildtype glioblastoma between 2012 and 2021. Co-primary outcomes were progression-free survival (PFS) and overall survival (OS), evaluated through Kaplan-Meier estimates and multivariable Cox models. Secondary 1:1 propensity score-matched analyses were performed based on age, preoperative KPS, MGMT methylation status, preoperative tumor volumes, and localization. Volumetric analysis included contrast-enhancing (CE) and non-CE tumor components. Subgroup analyses were stratified by tumor location. Results: In the unmatched cohort, IONM was independently associated with prolonged PFS (HR 0.60, 95% CI, 0.45-0.84) and OS (HR 0.60, 95% CI, 0.43-0.83), along with younger age, MGMT methylation, higher KPS, and smaller postoperative volumes. IONM patients had higher complete CE resection rates (64.2% vs 40.4%, P = .0005) and improved functional preservation (postoperative KPS 80 vs. 70, P = .008), despite more early deficits. In the location-matched cohort (n = 104), median PFS was 12 months with IONM vs 7 months without (P = .0007), and OS was 17 vs 11 months (P = .0018). Supramaximal resections occurred exclusively in the IONM group. The benefit was most evident in frontal, parietal, and insular tumors. Conclusions: IONM-supported surgery was associated with more extensive resection, functional preservation, and longer survival in IDH-wildtype glioblastoma. IONM was more frequently used in tumors located in frontal, parietal, and insular regions, consistent with the functional complexity of these areas.

Background/Objectives: Patients with unresectable glioblastoma (GBM) undergoing biopsy alone represent a clinically heterogeneous population with poor survival and limited access to standard oncological treatment. We investigated clinical, radiological, and histomolecular factors associated with early mortality after biopsy. Methods: We retrospectively analyzed 93 consecutive cases of patients with IDH-wildtype GBM who underwent biopsy without tumor resection between 2013 and 2025. Early death was defined as death within three months of biopsy. Baseline clinical, radiological, and molecular variables were evaluated using univariable analyses and exploratory multivariable logistic regression. Results: Median overall survival was 3 months, and 48/89 patients with available survival data (53.9%) died within three months. Preoperative Karnofsky Performance Status (KPS) and MGMT promoter methylation status (available for 71/93 patients) were nominally associated with early mortality in univariable analyses, although these associations did not remain significant after FDR correction. Age was not significant in univariable analysis but was associated with early mortality after adjustment in the exploratory multivariable model based on 62 complete cases. Conventional radiological parameters showed no consistent association with early death. Exploratory analysis suggested a high-risk phenotype combining KPS ≤ 60 and FLAIR signal crossing the midline. Overall, 23/93 patients (24.7%) did not initiate any adjuvant treatment, while only 17/93 (18.3%) completed the Stupp regimen. Conclusions: Early mortality is frequent in biopsy-only GBM. Clinical and molecular factors may help identify particularly vulnerable patients at diagnosis, supporting individualized treatment planning and shared decision-making. External validation in larger multicenter cohorts is warranted.

Background/Objectives: Recurrent glioblastoma has a poor prognosis and no universally accepted standard of care. Regorafenib has been investigated in this setting, but its use may be limited by treatment-related toxicity. This study evaluated the feasibility, safety, and clinical outcomes of reduced-dose regorafenib in patients with recurrent IDH-wildtype glioblastoma. Methods: We retrospectively analyzed 21 patients with recurrent IDH-wildtype glioblastoma (WHO 2021) treated at a single center after progression according to the Stupp protocol. Regorafenib was started at 80 mg/day on the standard 3-weeks-on/1-week-off schedule. We assessed overall survival from diagnosis (OS1) and from first progression (OS2), progression-free survival from diagnosis (PFS1) and from first progression (PFS2), treatment exposure, dose modifications, and treatment-related adverse events (CTCAE v5.0). Results: Median PFS2 was 5 months (95% CI, 3–8), median OS2 was 6 months (95% CI, 5–10), and median OS1 was 21 months (95% CI, 15–27). No grade ≥ 3 adverse events occurred, and no patient discontinued treatment permanently because of toxicity. Conclusions: In this retrospective single-center cohort, reduced-dose regorafenib was feasible and well tolerated in selected patients. These descriptive, hypothesis-generating findings warrant prospective studies to define the role of individualized regorafenib dosing in recurrent glioblastoma.

Background: Spheno-orbital meningiomas (SOMs) are challenging skull base tumors requiring a balance between oncologic control and functional–aesthetic outcomes. Endoscopic transorbital approaches (ETOA) have recently gained popularity as minimally invasive alternatives to standard transcranial techniques, but comparative evidence is lacking. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed/MEDLINE, Embase, and Scopus were searched from inception to the final search date. Studies reporting outcomes after ETOA or standard transcranial approaches were included. Primary outcomes included improvement in proptosis and visual function, extent of resection, and complications. Secondary outcomes included tumor progression and recurrence. Random-effects generalized linear mixed models were used to pool proportions. Mixed-effects meta-regression evaluated the association between approach and outcomes. Results: Fifty-three studies encompassing 2016 patients were included. A total of 155 (7.7%) ETOA and 1864 (92.3%) transcranial approaches were performed. Proptosis improvement was greater with ETOA (96% vs 72%) while visual improvement was similar (ETOA 31% vs standard 33%; p=0.857). Gross total resection (GTR) was lower with ETOA (21.1% vs 48.0%) and favored transcranial approaches after sensitivity analysis excluding influential studies (OR 5.00, p=0.047). Complication rates did not differ significantly between approaches, with a numerically lower rate observed after ETOA compared with standard transcranial surgery (18% vs 26%; p = 0.165). Median follow-up was shorter in the ETOA series (18 vs 52 months); recurrence and progression were lower after ETOA but likely influenced by follow-up duration. Conclusions: ETOA demonstrates superior proptosis improvement compared with standard transcranial approaches, comparable visual outcomes, and lower rates of GTR. Complication rates did not differ significantly. In appropriately selected SOMs, ETOA represents a valid surgical strategy within a tailored, goal-oriented approach, while standard transcranial techniques remain a workhorse for cases requiring extensive intracranial or dural control. Longer follow-up is required to clarify long-term tumor control.

Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m²; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework.

Objective: Stereo‐electroencephalography (SEEG) is designed to record gray matter (GM) activity for epileptogenic zone localization. SEEG electrodes, however, traverse white matter (WM) pathways that connect regions involved in seizure networks and cognition. We retrospectively evaluated WM tract sampling in patients with SEEG to identify pathways suitable for prospective WM stimulation studies and validated this in two patients. Methods: This retrospective analysis included 86 individuals who underwent SEEG implantation for drug‐resistant epilepsy between 2014 and 2020. Electrode contacts were localized using postoperative high‐resolution computed tomography (CT), co‐registered to preoperative 3T T1‐weighted magnetic resonance imaging (MRI) and normalized to Montreal Neurological Institute (MNI) space. Tissue classification utilized the Harvard–Oxford atlas, whereas WM tract involvement was assessed using probabilistic WM atlases. Preoperative tractography with dissection of the optic radiation was performed and used for 50 Hz, image‐guided SEEG stimulation of white matter. Results: Among 86 patients (30 left, 40 right, 16 bilateral hemisphere implantations), 860 electrodes (6372 contacts) were implanted. Of 5853 intraparenchymal contacts (92%), 1826 (31%) were positioned exclusively within WM and 2554 (44%) at the GM/WM boundary. Patients had an average of 10 electrodes (74 contacts). Of intraparenchymal contacts, 4381 (75%) crossed WM pathways (average 21 tracts per patient). The most frequently sampled tracts were commissural fibers (corpus callosum: 100% of patients), followed by association fibers including the inferior fronto‐occipital fasciculus (97.7%), superior longitudinal fasciculus II (96.5%), and cingulum (95.4%). In two separate patients, WM stimulation induced phosphenes at .5–1 mA in different distant electrodes with contacts in the optic radiation, which was reproducible and tract selective. Significance: SEEG electrodes sample WM structures in approximately two‐thirds of contacts, and association pathways demonstrate near‐universal sampling, making them optimal candidates for systematic WM stimulation protocols. SEEG–WM stimulation with preoperative tractography was validated in two different patients.