Stefano Borsa

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/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.

Purpose: To analyze the efficacy and safety of surgery compared to radiosurgery (RS), combined or not with whole brain radiotherapy (WBRT), for localized metastatic brain disease. Methods: A systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The inclusion criteria were limited to randomized controlled trials (RCTs) that compared surgery and RS for patients with up to 3 metastases (median diameter ≤ 4 cm). The primary outcomes were represented by overall survival (OS) and local brain progression-free survival (PFS), with the rate of complications as a secondary outcome. The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the RoB2 revised tool and the certainty of the evidence was assessed according to the GRADE guidelines. Results: In total, 11,256 records were identified through database and register searches. After study selection, 3 RCTs and 353 patients were included in the quantitative synthesis. Surgery and RS represented the main intervention arms in all the included RCTs. Conclusions: A low level of evidence suggests that RS alone and surgery followed by WBRT provide an equal rate of local brain PFS in patients with localized metastatic brain disease. There is a very low level of evidence that surgery and RS as main interventions offer equivalent OS in the population investigated. A reliable assessment of the complication rates among surgery and RS was not achievable. The lack of high-certainty evidence either for superiority or equivalence of these treatments emphasizes the need for further, more accurate, RCTs comparing surgery and RS as local treatment in patients with oligometastatic brain disease.

Background and Objective: To analyze the effects of several drug for pain prevention in adults undergoing craniotomy for elective brain surgery. Material and Methods: A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The inclusion criteria were limited to randomized controlled trials (RCTs) that evaluated the effectiveness of pharmacological treatments for preventing post-operative pain in adults (aged 18 years or older) undergoing craniotomies. The main outcome measures were represented by the mean differences in validated pain intensity scales administered at 6 h, 12 h, 24 h and 48 h post-operatively. The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the RoB2 revised tool, and the certainty of evidence was assessed according to the GRADE guidelines. Results: In total, 3359 records were identified through databases and registers’ searching. After study selection, 29 studies and 2376 patients were included in the meta-analysis. The overall risk of bias was low in 78.5% of the studies included. The pooled estimates of the following drug classes were provided: NSAIDs, acetaminophen, local anesthetics and steroids for scalp infiltration and scalp block, gabapentinoids and agonists of adrenal receptors. Conclusions: High-certainty evidence suggests that NSAIDs and acetaminophen may have a moderate effect on reducing post-craniotomy pain 24 h after surgery compared to control and that ropivacaine scalp block may have a bigger impact on reducing post-craniotomy pain 6 h after surgery compared to control. Moderate-certainty evidence indicates that NSAIDs may have a more remarkable effect on reducing post-craniotomy pain 12 h after surgery compared to control. No moderate-to-high-certainty evidence indicates effective treatments for post-craniotomy pain prevention 48 h after surgery.

(1) Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) represents a diagnostic and therapeutic challenge in neurosurgical practice, expanding the burden of care and exposing patients to additional risks related to further invasive procedures and treatment delays. In addition, atypical cases and overlapping features have not been entirely addressed by modern diagnostic research. The aim of this study was to validate a previously designed and internally validated ResNet101 deep learning model to differentiate glioblastomas, PCNSLs and BMs. (2) Methods: We enrolled 126 patients (glioblastoma: n = 64; PCNSL: n = 27; BM: n = 35) with preoperative T1Gd-MRI scans and histopathological confirmation. Each lesion was segmented, and all regions of interest were exported in a DICOM dataset. A pre-trained ResNet101 deep neural network model implemented in a previous work on 121 patients was externally validated on the current cohort to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. (3) Results: The model achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.73; 95%CI: 0.62–0.85), glioblastomas (AUC: 0.78; 95%CI: 0.71–0.87) and moderate to low ability in differentiating BMs (AUC: 0.63; 95%CI: 0.52–0.76). The performance of expert neuro-radiologists on conventional plus advanced MR imaging, assessed by retrospectively reviewing the diagnostic reports of the selected cohort of patients, was found superior in accuracy for BMs (89.69%) and not inferior for PCNSL (82.90%) and glioblastomas (84.09%). (4) Conclusions: We investigated whether the previously published deep learning model was generalizable to an external population recruited at a different institution—this validation confirmed the consistency of the model and laid the groundwork for future clinical applications in brain tumour classification. This artificial intelligence-based model might represent a valuable educational resource and, if largely replicated on prospective data, help physicians differentiate glioblastomas, PCNSL and solitary BMs, especially in settings with limited resources.

Object: To investigate those parameters affecting early and follow-up functional outcomes in patients undergoing resection of meningiomas and to design a dedicated predictive score, the Milan Bio(metric)-Surgical Score (MBSS) is hereby presented. Methods: Patients undergoing transcranial surgery for intracranial meningiomas were included. The most significant parameters in the regression analyses were implemented in a patient stratification score and were validated by testing its classification consistency with a clinical–radiological grading scale (CRGS), Milan complexity scale (MCS), and Charlson Comorbidity Index (CCI) scores. Results: The ASA score, Frailty index, skull base and posterior cranial fossa locations, a diameter of >25 mm, and the absence of a brain–tumour interface were predictive of early post-operative deterioration and were collected in MBSS Part A (AUC: 0.965; 95%C.I. 0.890–1.022), while the frailty index, posterior cranial fossa location, a diameter of >25 mm, a edema/tumour volume index of >2, dural sinus invasion, DWI hyperintensity, and the absence of a brain–tumour interface were predictive of a long-term unfavourable outcome and were collected in MBSS Part B (AUC: 0.877; 95%C.I. 0.811–0.942). The score was consistent with CRGS, MCS, and CCI. Conclusion: Patients’ multi-domain evaluation and the implementation of frailty indexes might help predict the perioperative complexity of cases; the functional, clinical, and neurological early outcomes; survival; and overall QoL after surgery.