FLAIRectomy in Supramarginal Resection of Glioblastoma Correlates With Clinical Outcome and Survival Analysis: A Prospective, Single Institution, Case Series

Abstract

Background Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival. Objective To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival. Methods A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared. Results FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68). Conclusion EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.

Diagnostic Utility of the Immunohistochemical Expression of Serine and Arginine Rich Splicing Factor 1 (SRSF1) in the Differential Diagnosis of Adult Gliomas

“…Assigning a histological grade was the only means of predicting the biological behavior of a CNS neoplasm. The 2016 World Health Organization (WHO) classification of CNS tumors introduced substantial changes to the previous morphology-based classification method [ 8 , 9 , 10 , 11 ]: the most important novelty was the introduction of “entity-defining” molecular alterations, such as chromosome 1p and 19q co-deletion for oligodendrogliomas [ 12 ]; the increasingly limited use of the diagnosis of “oligoastrocytoma”, restricted to cases in which molecular tests cannot be performed or are not conclusive [ 13 ]; the identification of specific mutations with both prognostic and diagnostic value, including the mutational status of the isocitrate dehydrogenase 1 and 2 genes ( IDH1/2 ) for adult astrocytomas [ 14 , 15 ]. In particular, IDH mutations represent the most important independent prognostic factor associated with a favorable outcome among adult diffuse gliomas, as IDH-mutant adult astrocytomas have a relatively better prognosis in terms of disease-free survival and overall survival than their IDH wild-type counterparts.…”

Quantitative Mapping of Individual Voxels in the Peritumoral Region of Glioblastoma to Distinguish Between Tumor Infiltration and Edema

“…A possible implication for pre-operative mapping of the PTR can be in surgical resection of regions with a likely higher burden of microscopic disease. Few studies had shown a potentially positive impact on survival in patients undergoing supratotal resection or "FLAIRectomy" [22,23]. Another potential application for the current study will be in guiding RT target volumes, speci cally targeting areas of in ltrative tumor, as the standard practice includes a wider margin in an empirical manner [24].…”

Peritumoral Microenvironment in High-Grade Gliomas: From FLAIRectomy to Microglia–Glioma Cross-Talk

“…Other study groups, instead, in a series of 245 and 64 patients did not find a survival improvement with FLAIRectomy [ 3 , 7 ]. On the contrary, we recently described in our single-center experience on 68 patients that a FLAIR-based EOR, in multivariate analyses comprising age, isocitrate dehydrogenase 1 (IDH-1) mutation, O6 methylguanine methyltrasferase (MGMT)-methylation, Radiotherapy (RT) dose, and the number of temozolomide cycles, appears to be a stronger survival predictor compared with EN resection [ 9 ]. In a detailed analysis of 585 cases, Jang et al found that HGGs probably explain the literature discrepancies.…”

“…Nevertheless, the present literature does not clearly define what is “supratotal resection” (SupTR), especially in high-grade gliomas (HGGs) [ 6 ]. Some authors have taken into consideration the FLAIR hyperintensity region beyond the enhancing nodule (EN), and it has been proven that this area has different biological features [ 6 , 7 , 8 , 9 , 10 , 11 ]. Ross et al demonstrated that glioblastoma (GBM) has three principal tumoral microenvironments—the perinecrotic region, bulk tumor (corresponding to EN), and the infiltrative tumor margin (partially corresponding to FLAIR hyperintensity areas).…”