Liver Cancer (Jul 2020)

Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials

  • Keisuke Koroki,
  • Sadahisa Ogasawara,
  • Yoshihiko Ooka,
  • Hiroaki Kanzaki,
  • Kengo Kanayama,
  • Susumu Maruta,
  • Takahiro Maeda,
  • Masayuki Yokoyama,
  • Toru Wakamatsu,
  • Masanori Inoue,
  • Kazufumi Kobayashi,
  • Soichiro Kiyono,
  • Masato Nakamura,
  • Naoya Kanogawa,
  • Tomoko Saito,
  • Takayuki Kondo,
  • Eiichiro Suzuki,
  • Shingo Nakamoto,
  • Shin Yasui,
  • Akinobu Tawada,
  • Tetsuhiro Chiba,
  • Makoto Arai,
  • Tatsuo Kanda,
  • Hitoshi Maruyama,
  • Jun Kato,
  • Satoshi Kuboki,
  • Masayuki Ohtsuka,
  • Masaru Miyazaki,
  • Osamu Yokosuka,
  • Naoya Kato

DOI
https://doi.org/10.1159/000508809

Abstract

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Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden. Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs. Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC. Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC. Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.

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