Supplementary Material for: Lenvatinib-Transarterial Chemoembolization Sequential Therapy as an Effective Treatment at Progression during Lenvatinib Therapy for Advanced Hepatocellular Carcinoma

<b><i>Background:</i></b> The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. <b><i>Results:</i></b> Heterogeneous enhancement patterns (<i>Type-3</i> and <i>-4</i>), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (<i>Type-2</i>) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (<i>p</i> = 0.313). Because of significantly worse PPS, overall survival of <i>Type-4</i> tumor was poor compared to <i>Type-2</i> or <i>-3</i> tumors (<i>p</i> = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01–0.71; <i>p</i> = 0.023), while <i>Type-4</i> enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06–8.05; <i>p</i> = 0.039). <b><i>Conclusion:</i></b> Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.