Abstract

Hepatocellular carcinoma (HCC) is a heterogeneous disease with many available treatment modalities. Transarterial chemoembolization (TACE) is a valuable treatment modality for HCC lesions. This article seeks to evaluate the utility of additional ablative therapy in the management of patients with HCC who received an initial TACE procedure. To compare the overall survival (OS) and freedom from local progression (FFLP) outcomes after TACE alone with TACE that is followed by an ablative treatment regimen using stereotactic body radiation therapy, radiofrequency ablation, or microwave ablation for patients with HCC. This cohort study of 289 adults at a single urban medical center examined survival outcomes for patients with nonmetastatic, unresectable HCC who received ablative therapies following TACE or TACE alone from January 2010 through December 2018. The Lee, Wei, Amato common baseline hazard model was applied for within-patient correlation with robust variance and Cox regression analysis was used to assess the association between treatment group (TACE vs TACE and ablative therapy) and failure time events (FFLP per individual lesion and OS per patient), respectively. In both analyses, the treatment indication was modeled as a time-varying covariate. Landmark analysis was used as a further sensitivity test for bias by treatment indication. TACE alone vs TACE followed by ablative therapy. Freedom from local progression and overall survival. Hypotheses were generated before data collection. Of the 289 patients identified, 176 (60.9%) received TACE only and 113 (39.1%) received TACE plus ablative therapy. Ablative therapy included 45 patients receiving stereotactic body radiation therapy, 39 receiving microwave ablation, 20 receiving radiofrequency ablation, and 9 receiving a combination of these following TACE. With a median (interquartile range) follow-up of 17.4 (9.5-29.5) months, 242 of 512 (47.3%) lesions progressed, 211 in the group with TACE alone and 31 in the group with TACE plus ablative therapy (P < .001). Over 3 years, FFLP was 28.1% for TACE alone vs 67.4% for TACE with ablative therapy (P < .001). The 1-year and 3-year OS was 87.5% and 47.1% for patients with lesions treated with TACE alone vs 98.7% and 85.3% for patients where any lesion received TACE plus ablative therapy, respectively (P = .01), and this benefit remained robust on landmark analyses at 6 and 12 months. The addition of ablative therapy was independently associated with OS on multivariable analysis for all patients (hazard ratio, 0.26; 95% CI, 0.13-0.49; P < .001) and for patients with Barcelona clinic liver cancer stage B or C disease (hazard ratio, 0.31; 95% CI, 0.14-0.69; P = .004). Adding ablative therapy following TACE improved FFLP and OS among patients with hepatocellular carcinoma. This study aims to guide the treatment paradigm for HCC patients until results from randomized clinical trials become available.

Highlights

  • Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fourth leading cause of cancer-related death worldwide, accounting for more than 782 000 total deaths in 2018.1 Transarterial chemoembolization (TACE) has been shown to improve the survival of patients with HCC compared with best supportive care in randomized clinical trials and meta-analyses conducted over the last 20 years

  • We evaluate the association of local ablative therapy using stereotactic body radiation therapy (SBRT), microwave ablation (MWA), or radio frequency ablation (RFA) given after TACE with the overall survival benefit

  • We found that the addition of an ablative treatment modality using either SBRT, MWA, or RFA following an initial TACE procedure in patients with newly diagnosed HCC was associated with improved overall survival and freedom from local progression

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fourth leading cause of cancer-related death worldwide, accounting for more than 782 000 total deaths in 2018.1 Transarterial chemoembolization (TACE) has been shown to improve the survival of patients with HCC compared with best supportive care in randomized clinical trials and meta-analyses conducted over the last 20 years. A 2002 randomized trial[2] found a survival advantage of conventional TACE when added to best supportive care (TACE, 28.6 months vs best supportive care, 17.9 months; P = .01). TACE as a solitary treatment rarely produces a complete response. Published data suggest that SBRT may be associated with a progression-free survival benefit, among patients with a lesser disease burden.[9]

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