A novel hybrid model for predicting tertiary lymphoid structures and targeted immunotherapy outcomes in hepatocellular carcinoma: a multicenter retrospective study

To develop a novel hybrid model for preoperative prediction of tertiary lymphoid structures (TLSs) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from postoperative targeted immunotherapy.

Retrospective data were gathered from 332 patients with HCC who underwent surgical resection and gadoxetate disodium (Gd-EOB-DTPA) enhanced MRI at two tertiary hospitals (training cohort, n = 205; internal validation cohort, n = 90; and external validation cohort, n = 37) between March 2020 and January 2023. Radiomic features were extracted from Gd-EOB-DTPA-enhanced MRI sequences. These signatures were integrated with clinical–radiologic (CR) factors into a hybrid model and nomogram for clinical application. The performance of the model was assessed using the area under the curve (AUC) and 95% confidence intervals (CI).

The hybrid model outperformed the radiomics and CR models in the training cohort (AUC = 0.860 [95% CI: 0.805, 0.904], 0.784 [95% CI: 0.721, 0.838], and 0.809 [95% CI: 0.748, 0.860]). The hybrid model showed optimal performance, with AUCs of 0.823 (95% CI: 0.728, 0.895) and 0.875 (95% CI: 0.725, 0.960) in the internal and external validation cohorts, respectively. The calibration curve demonstrated that the nomogram had good diagnostic ability, and decision curve analysis indicated good clinical utility across all cohorts. Importantly, patients with a predicted high risk of TLSs from the hybrid model gained a survival benefit from targeted immunotherapy.

The hybrid model showed satisfactory performance in predicting intra-tumoral TLS positivity and targeted immunotherapy benefit in patients with HCC, potentially assisting clinicians in selecting precise individualized therapies.

Question How can accurate preoperative risk stratification of tertiary lymphoid structures positivity HCC be achieved to support targeted immunotherapy decision-making?

Findings A hybrid model combining radiomics model and clinical–radiological model may be a reliable marker for predicting tertiary lymphoid structures positivity HCC.

Clinical relevance Using this hybrid model may be useful in predicting tertiary lymphoid structures and screening candidate patients for targeted immunotherapy based on multiparametric MRI, which has potential clinical value in guiding clinical decision-making and improving patient outcomes.