Tiantian Hua, Xi Zhang, Junjie Li, Ying Jin, Jun Qiu, Ying Liu, Ying Liu, Dan Cheng, Yunyun Duan, Xing Liu, Zhizheng Zhuo, Song Lin, Yaou Liu, Yaou Liu
BACKGROUND: The T2-FLAIR mismatch (T2FM) sign is a highly specific imaging biomarker for isocitrate dehydrogenase (IDH)-mutant astrocytomas; however, its strict definition limits clinical applicability. PURPOSE: To determine whether an expanded T2FM (eT2FM) phenotype could improve identification of IDH-mutant astrocytomas and capture prognostic and biological information. STUDY TYPE: Retrospective. POPULATION: 349 patients (50.14% male; mean age, 41.08 ± 10.40 years) with IDH-mutant astrocytomas. FIELD STRENGTH/SEQUENCE: 3 T, T1-weighted gradient-echo- or spin-echo-based images, and T2-weighted, T2 fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted images mainly acquired using spin-echo-based techniques. ASSESSMENT: The eT2FM phenotype was defined by incorporating spatially heterogeneous T2 FLAIR signals beyond the classic T2FM sign. Survival differences were compared between eT2FM and non-eT2FM tumors. Survival associations were evaluated. Metabolomic profiling was explored. STATISTICAL TESTS: Kaplan-Meier analysis, weighted log-rank test, Cox regression, and metabolomic analyses. Significance was set at p < 0.05. RESULTS: The eT2FM phenotype was identified in 116 of 349 patients (33.24%; mean age, 39.08 ± 9.51 years), exceeding classic T2FM (50/349, 14.33%; mean age, 36.40 ± 9.10 years). Kaplan-Meier analysis showed more favorable overall survival for eT2FM than non-eT2FM tumors, with restricted mean survival time (RMST) up to 36 months of 35.18 and 32.08 months, respectively (absolute difference, 3.10 months). Similar findings were observed in the external validation cohort, in which eT2FM phenotype was identified in 48 of 146 patients (32.88%; mean age, 37.77 ± 11.05 years). Kaplan-Meier analysis also showed more favorable overall survival for eT2FM than non-eT2FM tumors, with RMSTs of 36.00 and 33.81 months, respectively (absolute difference, 2.19 months). The eT2FM phenotype was associated with better prognosis in univariable Cox analysis (HR, 0.265; 95% CI, 0.120-0.585), but not independently in multivariable analysis (HR, 2.014; 95% CI, 0.380-10.673; p = 0.41). Exploratory metabolomics identified 1078 differentially abundant features between groups. DATA CONCLUSION: The eT2FM phenotype extends the clinical utility of classic T2FM sign and delineates a subgroup of IDH-mutant astrocytomas with favorable clinicopathologic features. TECHNICAL EFFICACY: Stage 4.