Functional, genomic, and radiographic associations with outcomes in IDH-mutant glioma: experience from a high-volume tumor center Restricted; Files Only

Abstract

Introduction:

Gliomas are tumors that arise from brain tissue. While the most common tumors are high-grade and diagnosis portends a poor prognosis, a recently-defined subset of glioma characterized by a mutation of isocitrate dehydrogenase gene (IDH-mutant) are low/intermediate grade. IDH-mutant gliomas represent a heterogenous group of tumors with differing outcomes. We have one of the largest single-institution experiences with patients with IDH-mutant glioma. The goal of this project was describe frailty, tumor genetic, and radiographic parameters that relate to outcomes within IDH-mutant glioma.

 

Methods:

We had three aims in defining outcomes within our IDH-mutant glioma cohort. We first collected frailty-specific measures and calculated Charlson Comorbidity Index (CCI) and 5-factor modified frailty index (mFI-5). We tested this as an exposure for outcomes of 30-day readmission and overall survival. For the second aim, we tested the exposure of copy number (CN) variation, a proxy for mutational burden within the tumor, for outcomes of overall survival and progression free survival. Finally, we created and compared deep-learning, neural-network algorithms with non-imaging and MR imaging-only parameters to predict the outcome for genetic lineage of IDH-mutant glioma (astrocytoma vs. oligodendroglioma).

 

Results:

Higher frailty was not associated with 30-day readmission, nor overall survival in our cohort of IDH-mutant glioma patients, except when their first operation was performed at our institution. Higher CN variation was associated with lower progression free survival. We were able to predict astrocytoma vs. oligodendroglioma lineage using our deep-learning, neural-network algorithm. The MR imaging-only parameters better predicted tumor type than non-imaging variables.

 

Conclusion:

We further described the roles of frailty, tumor genetics, and imaging-predicting exposures within our single-institution experience of IDH-mutant glioma. Most of our statistical analyses were underpowered to define meaningful associations, however, these findings may inform future, larger cohort analyses.

Table of Contents

Table of Contents

Introduction………………………………………………………………………………………..1

Background………………………………………………………………………………………..2

Methods……………………………………………………………………………………………9

Results……………………………………………………………………………………………20

Discussion………………………………………………………………………………………..27

References………………………………………………………………………………………..34

Tables……………………………………………………………………………………….....…41

Figures……………………………………………………………………………………….......49

About this Master's Thesis

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• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Oncology Health Sciences, Surgery Health Sciences, Epidemiology
Palavra-chave	Glioma Frailty
Committee Chair / Thesis Advisor	Jordan Kempker, Emory University
Committee Members	Tomas Garzon-Muvdi, Emory University Jeffrey Olson, Emory University

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