5-Aminolevulic acid-guided surgery (5-ALA-GS) improves the extent of resection (EoR) and progression-free survival in patients with glioblastoma multiforme (GBM). A single-center retrospective cohort study of adult patients with GBM who had surgical resection between 2013 and 2019, 5-ALA guided versus a non-5-ALA cohort. The primary outcome was the overall survival (OS). Secondary outcomes were EoR, performance status (PS), and new focal neurological deficit. Three hundred and forty-three patients were included: 253 patients in 5-ALA-GS group and 90 patients in the non-5-ALA-GS group. The OS (17.47 vs 10.63 months, P < .0001), postoperative PS (P < .0001), PS at 6 months (P = .002), new focal neurological deficit (23.3% vs 44.9%, P < .0001), and radiological EoR (gross total resection [GTR]—47.4% vs 22.9%, P < .0001) were significantly better in the 5-ALA-GS group compared to non-5-ALA-GS group. In multivariate analysis, use of 5-ALA (P = .003) and MGMT promoter methylation (P = .001) were significantly related with a better OS. In patients with radiological GTR, OS was also significantly better (P < .0001) in the 5-ALA-GS group compared to the non-5-ALA-GS group. 5-ALA-GS is associated with a significant improvement in the OS, PS after surgery and at 6 months, larger EoR, and fewer new motor deficits in patients with GBM.

Supratentorial function-eloquent brain tumour surgeries challenge the balance between maximal tumour resection and preservation of neurological function. This study aims to evaluate the efficacy of preoperative and intraoperative mapping techniques on resection outcomes and post-operative deficits. This systematic review and meta-analysis examined literature up to March 2023, sourced from PubMed, Embase, and Medline. Criteria for inclusion were studies on patients undergoing surgery for supratentorial brain tumours, comparing preoperative mapping only (POM), intraoperative neuromonitoring and mapping (IONM), and combined techniques (POM&IONM), excluding non-randomized controlled trials. Data extraction focused on rates of gross total resection (GTR) and focal neurological deficits (FNDs). The main outcomes, assessed through a random-effects model and Cochran's Q-test for subgroup analysis. The study protocol is published on PROSPERO CRD42024512306. 19 studies involving 992 patients were included. Systematic review with meta-analysis revealed a non-significantly higher average GTR rates for POM&IONM (49.13%) and POM (50.79%) compared to IONM alone (41.23%). Highest rates of GTR were achieved with tractography-guided resection in POM group (66.59% versus fMRI–20.00%, p = 0.0004), multimodal stimulation in IONM group (54.16% versus low frequency stimulation (LFS)–13.29%, p < 0.0001) and in POM&IONM group (65.88% versus LFS–37.77%, p = 0.0036). Within the same tumour histology–metastasis, high grade and low grade glioma–there are no differences in the GTR rates achieved in the different groups (p > 0.05). In language-eloquent tumours and in awake craniotomy techniques regardless of tumour functional eloquence, POM&IONM group had higher GTR when compared to IONM groups (language eloquent tumours–POM&IONM 43.31% versus IONM–15.09%, p = 0.022; awake craniotomy technique–POM&IONM–41.22% versus IONM–12.08%, p = 0.0006). Permanent FNDs were higher in the IONM group (IONM-73.0%; POM-29.6%; POM&IONM-33.7% of immediate postoperative deficits, p = 0.0010). A combined POM&IONM approach is responsible for higher rates of GTR in patients with language eloquent tumours and in both awake and asleep craniotomy techniques regardless of the tumour functional eloquence. The tumour histology is not relevant for differences in GTR rates among different mapping and monitoring strategies. Permanent postoperative FNDs are more likely with standalone utilization of IONM. Not applicable.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.