Intertumoral Heterogeneity Based on MRI Radiomic Features Estimates Recurrence in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) heterogeneity impacts prognosis, and imaging is a potential indicator.

Purpose: To characterize HCC image subtypes in MRI and correlate subtypes with recurrence.

Study type: Retrospective.

Population: A total of 440 patients (training cohort = 213, internal test cohort = 140, external test cohort = 87) from three centers.

Field strength/sequence: 1.5-T/3.0-T, fast/turbo spin-echo T₂-weighted, spin-echo echo-planar diffusion-weighted, contrast-enhanced three-dimensional gradient-recalled-echo T₁-weighted with extracellular agents (Gd-DTPA, Gd-DTPA-BMA, and Gd-BOPTA).

Assessment: Three-dimensional volume-of-interest of HCC was contoured on portal venous phase, then coregistered with precontrast and late arterial phases. Subtypes were identified using non-negative matrix factorization by analyzing radiomics features from volume-of-interests, and correlated with recurrence. Clinical (demographic and laboratory data), pathological, and radiologic features were compared across subtypes. Among clinical, radiologic features and subtypes, variables with variance inflation factor above 10 were excluded. Variables (P < 0.10) in univariate Cox regression were included in stepwise multivariate analysis. Three recurrence estimation models were built: clinical-radiologic model, subtype model, hybrid model integrating clinical-radiologic characteristics, and subtypes.

Statistical tests: Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, Fisher's exact test, Kaplan-Meier curves, log-rank test, concordance index (C-index). Significance level: P < 0.05.

Results: Two subtypes were identified across three cohorts (subtype 1:subtype 2 of 86:127, 60:80, and 36:51, respectively). Subtype 1 showed higher microvascular invasion (MVI)-positive rates (53%-57% vs. 26%-31%), and worse recurrence-free survival. Hazard ratio (HR) for the subtype is 6.10 in subtype model. Clinical-radiologic model included alpha-fetoprotein (HR: 3.01), macrovascular invasion (HR: 2.32), nonsmooth tumor margin (HR: 1.81), rim enhancement (HR: 3.13), and intratumoral artery (HR: 2.21). Hybrid model included alpha-fetoprotein (HR: 2.70), nonsmooth tumor margin (HR: 1.51), rim enhancement (HR: 3.25), and subtypes (HR: 5.34). Subtype model was comparable to clinical-radiologic model (C-index: 0.71-0.73 vs. 0.71-0.73), but hybrid model outperformed both (C-index: 0.77-0.79).

Conclusion: MRI radiomics-based clustering identified two HCC subtypes with distinct MVI status and recurrence-free survival. Hybrid model showed superior capability to estimate recurrence.

Level of evidence: 3 TECHNICAL EFFICACY STAGE: 2.