Hepatocellular carcinoma (HCC) represents the commonest primary liver malignancy, and the fourth deadliest cancer around the world [1]. HCC prognosis remains poor, mainly because of a high diagnostic rate at an advanced disease stage. Moreover, therapeutic options for these patients are generally limited to systemic treatment [2,3]. Currently, there are many novel anticancer agents with demonstrated effectiveness. Sorafenib, the first approved systemic drug for HCC, improves patient survival [4]; in addition, the multitarget tyrosine kinase inhibitor (TKI) lenvatinib with anti-angiogenic effects, was proven to be non-inferior to sorafenib as first-line therapy for advanced-stage HCC in the REFLECT trial [5]. In recent years, immunotherapy applying checkpoint blockade inhibitors has renewed hope in HCC therapy, but with mixed results [6,7]. Lately, combined targeted and immunotherapy with TKIs and anti-programmed cell death protein 1 (PD-1) antibodies has revealed synergistic effects with promising results [[8], [9], [10]], with superiority over both TKI monotherapy [5,11] and single-agent anti-PD-1 antibody alone [6,7]. Yet, differential response to treatment has been reported with frequently detected primary or secondary resistance. Furthermore, these treatments are associated with unavoidable adverse events. Predicting various responses pre-treatment could help opt for more targeted treatments and optimize individual treatment strategies.

Among existing tools that are commonly used, biopsy is an invasive procedure with several risks and limitations [12], while serum testing lacks specificity [13]. Thus, identifying a reliable non-invasive imaging biomarker is of paramount importance in the search for effective therapeutic candidates. Nowadays, multiphase contrast-enhanced MRI is considered the most accurate tool in HCC imaging [14]. Recently reported findings suggested MRI as a good method for evaluating HCC prognosis [[15], [16], [17], [18], [19]], but this technique has been seldom applied for assessing the efficacy of combined targeted immunotherapy in HCC.

The present work aimed to assess the value of pre-treatment MRI in predicting treatment response to combined targeted immunotherapy in advanced HCC.