Association of Neurological Impairment on the Relative Benefit of Maximal Extent of Resection in Chemoradiation-Treated Newly Diagnosed Isocitrate Dehydrogenase Wild-Type Glioblastoma

Abstract

BACKGROUND:Increases in the extent of resection of both contrast-enhanced (CE) and non–contrast-enhanced (NCE) tissue are associated with substantial survival benefits in patients with isocitrate dehydrogenase wild-type glioblastoma. The fact, however, remains that these lesions exist within the framework of complex neural circuitry subserving cognition, movement, and behavior, all of which affect the ultimate survival outcome. The prognostic significance of the interplay between CE and NCE cytoreduction and neurological morbidity is poorly understood.OBJECTIVE:To identify a clinically homogenous population of 228 patients with newly diagnosed isocitrate dehydrogenase wild-type glioblastoma, all of whom underwent maximal safe resection of CE and NCE tissue and adjuvant chemoradiation. We then set out to delineate the competing interactions between resection of CE and NCE tissue and postoperative neurological impairment with respect to overall survival.METHODS:Nonparametric multivariate models of survival were generated via recursive partitioning to provide a clinically intuitive framework for the prognostication and surgical management of such patients.RESULTS:We demonstrated that the presence of a new postoperative neurological impairment was the key factor in predicting survival outcomes across the entire cohort. Patients older than 60 yr who suffered from at least one new impairment had the worst survival outcome regardless of extent of resection (median of 11.6 mo), whereas those who did not develop a new impairment had the best outcome (median of 28.4 mo) so long as all CE tissue was resected.CONCLUSION:Our data provide novel evidence for management strategies that prioritize safe and complete resection of CE tissue.

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

“…1,2 Prior studies provided evidence that larger extent of resection (EOR) is associated with more favorable outcome. [3][4][5][6][7] However, the terminology used to describe EOR has been inconsistently applied across clinical studies; hampering comparative analyses between different reports or institutions. Here, EOR has often been defined based upon the proportion of removed tumor although more recent studies suggest that the absolute residual tumor volume might be prognostically more relevant.…”

Technical Aspects of Motor and Language Mapping in Glioma Patients

“…Maximal safe resection is defined as resecting as much tumor-infiltrated tissue as possible to improve survival while minimizing the risk of postoperative neurological deficits and retaining quality of life [ 2 , 25 , 26 , 27 ]. As mentioned, SpTR has recently been associated with improved overall survival (OS) for both LGG and GBM [ 2 , 28 ]; however, the survival advantage of these more aggressive resections is lost when patients have a postoperative deficit [ 8 , 9 , 10 ]. As such, significant efforts have been made to develop pre- and intra-operative methods for maximizing EOR.…”

“…During tumor resection, the primary goal is to maximize the extent of resection—often performing a supratotal resection (SpTR) of lesional tissue when possible—while also preserving neurological function and patient quality of life [ 2 , 3 , 4 , 5 , 6 , 7 ]. The benefit of aggressive surgical resections must be balanced with the preservation of neurological function, as neurological deficits, particularly hemiparesis, have been shown to abrogate the procedure’s survival benefits [ 8 , 9 , 10 ].…”

Involvement of White Matter Language Tracts in Glioma: Clinical Implications, Operative Management, and Functional Recovery After Injury

“…However, the benefits of maximal resection are limited by the risks of iatrogenic injury to eloquent structures, or those that subserve motor, sensory, language, and cognitive processing and whose injury leads to potentially permanent functional impairment. Indeed, the development of postoperative neurological impairment not only negatively impacts quality of life, but is also associated with worse survival ( McGirt et al, 2009 ; Hervey-Jumper et al, 2015 ; Hervey-Jumper and Berger, 2016 ; Rahman et al, 2016 ; De Witt Hamer et al, 2021 ; Aabedi et al, 2022b ). This balance is especially challenging to achieve when eloquent white matter tracts are involved in the tumor as they are classically thought to be less resilient to injury and possess less plasticity or recovery potential in comparison to eloquent cortex ( Ius et al, 2011 ; Hamer et al, 2013 ).…”