Citations

Abstract Background Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas. Methods Targeted gene expression profiling was performed on 173 meningiomas and an optimized gene expression biomarker (34 genes) and risk score (0 to 1) was developed to predict clinical outcomes. Clinical and analytical validation was performed on independent meningiomas from 12 institutions across 3 continents (N = 1856), including 103 meningiomas from a prospective clinical trial. Gene expression biomarker performance was compared to 9 other classification systems. Results The gene expression biomarker improved discrimination of postoperative meningioma outcomes compared to all other classification systems tested in the independent clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). The increase in area under the curve compared to the current standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07–0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% CI 0.37–0.78, P = 0.0001) and re-classified up to 52.0% meningiomas compared to conventional clinical criteria, suggesting postoperative management could be refined for 29.8% of patients. Conclusions A targeted gene expression biomarker improves discrimination of meningioma outcomes compared to recent classification systems and predicts postoperative radiotherapy responses.

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.