T2-FLAIR mismatch sign predicts DNA methylation subclass and CDKN2A/B status in IDH-mutant astrocytomas.

in Clinical cancer research : an official journal of the American Association for Cancer Research by Matthew D Lee, Rajan Jain, Kristyn Galbraith, Anna Chen, Evan Lieberman, Sohil H Patel, Dimitris G Placantonakis, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, John G Golfinos, Daniel A Orringer, Matija Snuderl

TLDR

  • The study looked at how well a specific sign on an MRI scan (T2-FLAIR mismatch) could predict the grade of a type of brain tumor called IDH-mutant astrocytoma. The study found that the T2-FLAIR mismatch sign was very specific for predicting low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas. This means that if a patient has this sign on their MRI scan, it is likely that their tumor has a specific genetic makeup. The study also found that the T2-FLAIR mismatch sign could be used to predict the response to treatment in IDH-mutant astrocytomas. This means that if a patient has this sign on their MRI scan, it is likely that they will respond well to certain treatments. However, more research is needed to confirm these findings and to see if the T2-FLAIR mismatch sign can be used in other types of brain tumors.

Abstract

DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low-grade and high-grade groups. We investigated the utility of the T2-FLAIR mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization (WHO) classification. Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n=71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed. The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (p<0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (p=0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for PFS (p=0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, CNV, and methylation grade, showed trends toward significance for DNA methylation grade with OS (p=0.045) and CDKN2A/B status with PFS (p=0.052). The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.

Overview

  • The study investigates the utility of the T2-FLAIR mismatch sign for predicting DNA methylation grade and CDKN2A/B homozygous deletion in IDH-mutant astrocytomas according to the 2021 WHO classification. The study used preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n=71) and evaluated the T2-FLAIR mismatch sign by two radiologists. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed. The primary objective of the study is to determine the utility of the T2-FLAIR mismatch sign in predicting DNA methylation grade and CDKN2A/B homozygous deletion in IDH-mutant astrocytomas.

Comparative Analysis & Findings

  • The T2-FLAIR mismatch sign was present in 46.7% of methylation low-grade and 3.9% of methylation high-grade cases, resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for PFS (p=0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, CNV, and methylation grade, showed trends toward significance for DNA methylation grade with OS (p=0.045) and CDKN2A/B status with PFS (p=0.052). The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.

Implications and Future Directions

  • The study's findings suggest that the T2-FLAIR mismatch sign can be used to predict DNA methylation grade and CDKN2A/B homozygous deletion in IDH-mutant astrocytomas. The study's findings can be used to improve the accuracy of diagnosis and prognosis of IDH-mutant astrocytomas. Future research should investigate the utility of the T2-FLAIR mismatch sign in other subtypes of astrocytomas and in other brain tumors. Future research should also investigate the utility of the T2-FLAIR mismatch sign in predicting response to treatment in IDH-mutant astrocytomas.
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