Published online Dec 21, 2021. doi: 10.3748/wjg.v27.i47.8166
Peer-review started: March 22, 2021
First decision: June 14, 2021
Revised: July 28, 2021
Accepted: December 8, 2021
Article in press: December 8, 2021
Published online: December 21, 2021
Impressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals’ disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden.
To assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients.
This retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib.
The median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone.
TARE with/without sorafenib according to individuals’ disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.
Core Tip: Hepatocellular carcinoma (HCC) patients treated with yttrium-90 transarterial radioembolization (TARE) alone for intrahepatic tumor load ≤ 50% and TARE with sorafenib for intrahepatic tumor load > 50% and/or present macrovascular invasion, extrahepatic disease or infiltrative HCC yielded acceptable disease control rates of 79.4% and 71.6%, respectively. Between these 2 subgroups, incidence of intrahepatic progression was comparable (about 40%) but extrahepatic progression was much less common with TARE alone (12.7% vs 32%). Strategies that improve intrahepatic control for liver-only disease (dosimetry-based TARE) and extrahepatic control for metastatic disease (additional systemic therapy) could improve TARE outcome for unresectable HCC patients.