Is Flairectomy Directly Correlated with Prolonged Survival in Glioblastoma? A Prospective Italian Multicenter Study

Introduction: Supramarginal resection of glioblastoma, when safely feasible, is a surgical strategy aiming at including the FLAIR (Fluid Attenuated Inversion Recovery) positive area surrounding the gadolinium-enhancing tumor. Several papers have demonstrated a positive correlation between glioblastoma supramarginal resection, based on MRI FLAIR sequences (i.e. FLAIRectomy), and prolonged survival.
This study analyses the efficacy, safety and reliability of FLAIRectomy in a multicentric cohort of patients, correlating the extent of FLAIR resection (EOFR) with clinical outcome and survival.

Methods: One-hundred-fifty glioblastoma patients (82 male), with a mean age of 58.2 years (range 36-82), from three Italian neurosurgical centers were included. In all cases, supramarginal resection was deemed feasible pre-operatively; multicentric neoplasms or tumors infiltrating eloquent areas were excluded. Analysis of EOFR was based on comparison between pre- and post-operative 3D FLAIR images. EOFR was compared with Extent of resection (EOR) based on gadolinium-enhanced T1 sequences; theses data were also statistically correlated with survival parameters as well as with clinical and biomolecular data.

Results: Statistically significant differences in demographic features among the three centers group of patients were not found. EOFR rate was 78.8% in the entire cohort, whereas EOTR based on T1 sequences was 98.3%. Mean Progression free survival (PFS) and Overall Survival were 16.33 and 28.4 months, respectively. Adjusted multivariate Cox regression model showed a positive correlation between mumber of temozolomide cycles and EOFR. More precisely, the risk of mortality decreased by 27.2% and 7.6% with each one-unit increase in the number of TMZ cycles and in the EOFR, respectively
Further analysis based on artificial intelligence, demonstrated that the cluster of patients with higher values of PFS and OS received greater rate of FLAIRectomy.

Conclusion : This multicenter study demonstrates that EOFR is a more reliable predictor of PFS and OS than EOR based on gadolinium-enhanced T1 sequences, particularly if supramarginal resection is carried out according to specific pre-operative planning. 3D FLAIR navigation-guided resection may represent the optimal strategy to achieve a real FLAIRectomy.