Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302

Masafumi Ikeda; Yasuaki Arai; Yoshitaka Inaba; Toshihiro Tanaka; Shunsuke Sugawara; Yoshihisa Kodama; Takeshi Aramaki; Hiroshi Anai; Shinichi Morita; Yoshinori Tsukahara; Hiroshi Seki; Mikio Sato; Kenya Kamimura; Kimei Azama; Masakatsu Tsurusaki; Eiji Sugihara; Masaya Miyazaki; Tatsushi Kobayashi; Miyuki Sone

doi:10.1159/000525500

Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302

Liver Cancer. 2022 Jun 15;11(5):440-450. doi: 10.1159/000525500. eCollection 2022 Sep.

Authors

Masafumi Ikeda¹, Yasuaki Arai², Yoshitaka Inaba³, Toshihiro Tanaka⁴, Shunsuke Sugawara⁵, Yoshihisa Kodama⁶, Takeshi Aramaki⁷, Hiroshi Anai⁸, Shinichi Morita⁹, Yoshinori Tsukahara¹⁰, Hiroshi Seki¹¹, Mikio Sato¹², Kenya Kamimura¹³, Kimei Azama¹⁴, Masakatsu Tsurusaki¹⁵, Eiji Sugihara¹⁶, Masaya Miyazaki¹⁷, Tatsushi Kobayashi¹⁸, Miyuki Sone⁵

Affiliations

¹ Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
² Executive Advisor to the President, National Cancer Center, Tokyo, Japan.
³ Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan.
⁴ Department of Radiology, IVR Center, Nara Medical University, Kashihara, Japan.
⁵ Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Department of Radiology, Teine Keijinkai Hospital, Sapporo, Japan.
⁷ Division of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan.
⁸ Department of Radiology, Nara City Hospital, Nara, Japan.
⁹ Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Hospital, Minamiuonuma, Japan.
¹⁰ Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan.
¹¹ Department of Diagnostic Radiology, Niigata Cancer Center Hospital, Niigata, Japan.
¹² Department of Gastroenterology and Hepatology, Ryugasaki Saiseikai Hospital, Ryugasaki, Japan.
¹³ Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
¹⁴ Department of Radiology, Ryukyu University Hospital, Nishihara, Japan.
¹⁵ Department of Radiology, Kindai University Faculty of Medicine, Osaka-sayama, Japan.
¹⁶ Department of Diagnostic Imaging, Osaka General Medical Center, Osaka, Japan.
¹⁷ Department of Applied Medical Imaging, Gunma University Graduate School of Medicine, Maebashi, Japan.
¹⁸ Department of Diagnostic Radiology, National Cancer Center Hospital East, Kashiwa, Japan.

Abstract

Introduction: With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC.

Methods: Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events.

Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p = 0.0001), fatigue (5.1% vs. 15.8%, p = 0.0194), malaise (11.1% vs. 25.7%, p = 0.0103), appetite loss (12.1% vs. 28.7%, p = 0.0048), abdominal pain (12.1% vs. 23.8%, p = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, p = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, p = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm.

Conclusions: Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.

Keywords: Drug-eluting beads; Epirubicin; Ethiodized oil; Hepatocellular carcinoma; Transarterial chemoembolization.