Tumor response assessment in hepatocellular carcinoma treated with immunotherapy: imaging biomarkers for clinical decision-making

Abstract

Objective: To compare the performance of 1D and 3D tumor response assessment for predicting median overall survival (mOS) in patients who underwent immunotherapy for hepatocellular carcinoma (HCC).

Methods: Patients with HCC who underwent immunotherapy between 2017 and 2023 and received multi-phasic contrast-enhanced MRIs pre- and post-treatment were included in this retrospective study. Tumor response was measured using 1D, RECIST 1.1, and mRECIST, and 3D, volumetric, and percentage quantitative EASL (vqEASL and %qEASL). Patients were grouped into disease control vs progression and responders vs non-responders. Kaplan-Meier curves analyzed with log-rank tests assessed the predictive value for mOS. Cox regression modeling evaluated the association of clinical baseline parameters with mOS.

Results: This study included 37 patients (mean age, 69.1 years [SD, 8.0]; 33 men). The mOS was 16.9 months. 3D vqEASL and %qEASL successfully stratified patients into disease control and progression (vqEASL: HR 0.21, CI: 0.55-0.08, p < 0.001; %qEASL: HR 0.18, CI: 0.83-0.04, p = 0.013), as well as responder and nonresponder (vqEASL: HR 0.25, CI: 0.08-0.74, p = 0.007; %qEASL: HR 0.17, CI: 0.04-0.72, p = 0.007) for predicting mOS. The 1D criteria, mRECIST stratified into disease control and progression only (HR 0.24, CI: 0.65-0.09, p = 0.002), and RECIST 1.1 showed no predictive value in either stratification. Multivariate Cox regression identified alpha-fetoprotein > 500 ng/mL as a predictor for poor mOS (p = 0.04).

Conclusion: The 3D quantitative enhancement-based response assessment tool qEASL can predict overall survival in patients undergoing immunotherapy for HCC and could identify non-responders.

Clinical relevance statement: Using 3D quantitative enhancement-based tumor response criteria (qEASL), radiologists' predictions of tumor response in patients undergoing immunotherapy for HCC can be further improved.

Key points: MRI-based tumor response criteria predict immunotherapy survival benefits in HCC patients. 3D tumor response assessment methods surpass current evaluation criteria in predicting overall survival during HCC immunotherapy. Enhancement-based 3D tumor response criteria are robust prognosticators of survival for HCC patients on immunotherapy.

Keywords: Hepatocellular carcinoma; Immune checkpoint inhibitors; Magnetic resonance imaging; Treatment outcome.