Cognitive impairment three months after surgery is an independent predictor of survival time in glioblastoma patients

Elke Butterbrod,Karin Gehring,Inga Schwabe,Margriet Sitskoorn,Nathalie Synhaeve,Geert-Jan Rutten

doi:10.1007/s11060-020-03577-7

Abstract

PurposeCognitive functioning is increasingly investigated for its prognostic value in glioblastoma (GBM) patients, but the association of cognitive status during early adjuvant treatment with survival time is unclear. The aim of this study was to determine whether cognitive performance three months after surgical resection predicted survival time, while using a clinically intuitive time ratio (TR) statistic.MethodsNewly diagnosed patients with GBM undergoing resection between November 2010 and February 2018 completed computerized cognitive assessment 3 months after surgery with the CNS Vital Signs battery (8 measures). The association of cognitive performance (continuous Z scores and dichotomous impairment status; impaired vs. unimpaired) with survival time was assessed with multivariate Accelerated Failure Time (AFT) models that also included clinical prognostic factors and covariates related to cognitive performances.Results114 patients were included in the analyses (median survival time 16.4 months). Of the clinical factors, postoperative Karnofsky Performance Status (TR 1.51), surgical (TR 2.20) and non-surgical (TR 1.94) salvage treatment, and pre-surgical tumor volume (cm3, TR 1.003) were significant independent predictors of survival time. Independently of the base model factors and covariates, impairment on Stroop test I and Stroop test III estimated 23% and 26% reduction of survival time (TR 0.77, TR 0.74) respectively, as compared to unimpaired performance.ConclusionThese findings suggest that impaired performances on tests of executive control and processing speed in the early phase of adjuvant treatment can reflect a worse prognostic outlook rather than an early treatment effect, and their assessment might allow for early refinement of current prognostic stratification.

Highlights

To date, functional performance status (PS) appears to be one of the few clinical factors consistently allowing for prognostic stratification in the glioblastoma (GBM) population [1,2,3]
Before running the cognitive models, we investigated potential covariates: sex, low educational level, high educational level, affected hemisphere, frontal involvement, corticosteroid use at T3, anti-epileptic drug (AED) use at T3, and the clinical factors that were not significant predictors in the base model
This study investigated to what extent cognitive performance three months after surgical resection was related to survival time in patients with GBM

Summary

Introduction

Functional performance status (PS) appears to be one of the few clinical factors consistently allowing for prognostic stratification in the glioblastoma (GBM) population [1,2,3]. Journal of Neuro-Oncology (2020) 149:103–111 predictive value compared to characteristics such as macroscopic extent of resection [1] and patient age [3, 6]. Poorer cognitive performance in treatment- naive patients appears to predict worse survival outcome [10, 11]. Not all patients can be tested (validly) in the short period between diagnosis and start of treatment, and pre-treatment cognitive dysfunction may reflect tumor status [9, 12], its nature or severity may be affected by distress from the diagnosis [9, 13] tumor laterality [14], or motor symptoms [12, 13]

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