Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2021; 27(47): 8166-8181
Published online Dec 21, 2021. doi: 10.3748/wjg.v27.i47.8166
Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib
Ajalaya Teyateeti, Armeen Mahvash, James Long, Mohamed Abdelsalam, Rony Avritscher, Ahmed Kaseb, Bruno Odisio, Gregory Ravizzini, Devaki Surasi, Achiraya Teyateeti, Homer Macapinlac, Srinivas Cheenu Kappadath
Ajalaya Teyateeti, Gregory Ravizzini, Devaki Surasi, Homer Macapinlac, Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Ajalaya Teyateeti, Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Armeen Mahvash, Mohamed Abdelsalam, Rony Avritscher, Bruno Odisio, Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
James Long, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Ahmed Kaseb, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Achiraya Teyateeti, Division of Radiation Oncology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Srinivas Cheenu Kappadath, Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Author contributions: Teyateeti A designed the study, collected, analyzed and interpreted the data and wrote the manuscript; Mahvash A, Abdelsalam M, Avritscher R, Odisio B, Ravizzini G, and Surasi D collected data, provided clinical advice and edited the manuscript; Long J supervised and provided advice for statistical analysis and edited the manuscript; Kaseb A and Macapinlac H edited the manuscript; Teyateeti A contributed to study design, provided clinical advice and made critical revision of the manuscrip; and Kappadath SC contributed to the design of the study, interpretation of the data, made critical revision of the manuscript and supervised the study.
Institutional review board statement: This study was approved by Institutional review board of The University of Texas MD Anderson Cancer Center, No. DR09-0025.
Informed consent statement: A waiver of informed consent was granted by our Institutional Review Board for this retrospective study. Patient data used complied with all institutional data protection and privacy regulations.
Conflict-of-interest statement: All authors have no any conflicts of interest.
Data sharing statement: Authors are open to data sharing, please email queries.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Srinivas Cheenu Kappadath, PhD, Professor, Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1155 Pressler St, Unit 1352, Houston, TX 77030, United States. skappadath@mdanderson.org
Received: March 22, 2021
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
Abstract
BACKGROUND

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.

AIM

To assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Radioembolization, Selective internal radiotherapy, Tumor response, Pattern of progression, Time to progression, Sorafenib

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.