Predictive accuracy of T2-FLAIR mismatch sign for the IDH-mutant, 1p/19q noncodeleted low-grade glioma: An updated systematic review and meta-analysis

Abstract

Background The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, has been considered a highly specific imaging biomarker of IDH-mutant, 1p/19q non-codeleted low grade glioma. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of T2-FLAIR mismatch sign for prediction of a patient with IDH-mutant, 1p/19q non-codeleted low grade glioma, and identify the causes responsible for the heterogeneity across the included studies. Methods A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before November 17, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Meta-regression analyses were also performed to determine factors influencing heterogeneity. Results For all the 10 included cohorts from 8 studies, the pooled sensitivity was 40% (95% confidence interval [CI] 28–53%), and the pooled specificity was 100% (95% CI 95–100%). In the hierarchic summary receiver operating characteristic curve, the difference between the 95% confidence and prediction regions was relatively large, indicating heterogeneity among the studies. Higgins I 2 statistics demonstrated considerable heterogeneity in sensitivity (I 2 = 83.5%) and considerable heterogeneity in specificity (I 2 = 95.83%). Among the potential covariates, it seemed that none of factors was significantly associated with study heterogeneity in the joint model. However, the specificity was increased in studies with all the factors based on the differences of the composition of the detailed tumors. Conclusions The T2-FLAIR mismatch sign is near-perfect specific marker of IDH mutation and 1p/19q non-codeletion.

The T2‐FLAIR mismatch sign as an imaging biomarker for oligodendrogliomas in dogs

“…Although MRI features compatible with the T2FMM sign previously were included in a study of oligodendrogliomas in dogs, ours is the first study that specifically identified a significant relationship between an MRI biomarker and the oligodendroglial phenotype in dogs 18 . In adult humans, the T2FMM sign is a highly accurate biomarker for IDH1‐mutated, 1p/19q non‐codeleted astrocytomas, with specificity and sensitivity as high as 100% and 31%, respectively 8‐12 . We found a similar high specificity and low sensitivity for the T2FMM to detect oligodendrogliomas in dogs.…”

“…Glioma classification in humans is based on 2021 World Health Organization criteria, including genotypic, molecular and phenotypic tumor features, describing entities in which the presence of isocitrate dehydrogenase 1/2 (IDH1/2) mutations and 1p/19q codeletion status are considered important predictors of positive prognosis and longer overall survival than are found in patients carrying the wild‐type IDH1/2 gene 5‐7 . Genomic features of gliomas in humans also have been associated with certain magnetic resonance imaging (MRI) biomarkers such as the T2‐weighted (T2W)—fluid‐attenuated inversion recovery (FLAIR) mismatch (T2FMM) sign, which has high to perfect specificity and moderate to low sensitivity to predict IDH1‐mutant, 1p/19q non‐codeleted low‐grade astrocytomas (LGA) 8‐13 . The T2FMM is characterized by a homogeneous hyperintense signal on T2W and a hypointense signal with a hyperintense peripheral rim on FLAIR 8,13 …”

“…[5][6][7] Genomic features of gliomas in humans also have been associated with certain magnetic resonance imaging (MRI) biomarkers such as the T2-weighted (T2W)-fluid-attenuated inversion recovery (FLAIR) mismatch (T2FMM) sign, which has high to perfect specificity and moderate to low sensitivity to predict IDH1-mutant, 1p/19q non-codeleted low-grade astrocytomas (LGA). [8][9][10][11][12][13] The T2FMM is characterized by a homogeneous hyperintense signal on T2W and a hypointense signal with a hyperintense peripheral rim on FLAIR. 8,13 Although histopathology is the gold standard to diagnose gliomas, antemortem diagnosis by biopsy rarely is performed in veterinary medicine because of practical limitations, such as availability of centers with experience performing brain biopsy or surgery in dogs with gliomas.…”

T2-fluid attenuated inversion recovery mismatch in tumefactive multiple sclerosis

“…In a metanalysis of 10 cohorts across 8 studies, a pooled specificity of 100% was reported. 3 However, the application of this imaging finding is at times questionable in clinical practice. At the initial imaging interpretation, the primary question is often not the molecular status of the glial neoplasm, but whether the observed lesion is a glioma.…”

Editorial comment: “Diffuse glioma, not otherwise specified: imaging-based risk stratification achieves histomolecular-level prognostication”

“…Various signs have been identified that can help to predict the molecular status of glioma in the daily clinical setting. For example, the famous T2/FLAIR mismatch signshowing low sensitivity but high specificity for IDH-mutant astrocytoma [3] has been proven to be a reliable marker. Prior to the present, differentiation and prognostic analysis of high-grade glioma from low-grade glioma were the major topics of research.…”