Survival Outcomes Associated With Radiological Progressive Disease Subtypes in Patients With Atezolizumab and Bevacizumab–Treated HCC
Tomomitsu Matono
Department of Gastroenterology, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Hyogo, Japan
Search for more papers by this authorCorresponding Author
Toshifumi Tada
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
Correspondence:
Toshifumi Tada ([email protected])
Search for more papers by this authorTakashi Kumada
Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
Search for more papers by this authorAtsushi Hiraoka
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
Search for more papers by this authorMasashi Hirooka
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorKazuya Kariyama
Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
Search for more papers by this authorJoji Tani
Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan
Search for more papers by this authorMasanori Atsukawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorKoichi Takaguchi
Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorEi Itobayashi
Department of Gastroenterology, Asahi General Hospital, Chiba, Japan
Search for more papers by this authorShinya Fukunishi
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorHiroki Nishikawa
Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan
Search for more papers by this authorKazunari Tanaka
Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan
Search for more papers by this authorKunihiko Tsuji
Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan
Search for more papers by this authorToru Ishikawa
Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
Search for more papers by this authorKazuto Tajiri
Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorYuichi Koshiyama
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
Search for more papers by this authorHidenori Toyoda
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
Search for more papers by this authorChikara Ogawa
Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorTakeshi Hatanaka
Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan
Search for more papers by this authorSatoru Kakizaki
Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
Search for more papers by this authorKazuhito Kawata
Department of Hepatology, Hamamatsu University School of Medicine, Shizuoka, Japan
Search for more papers by this authorHideko Ohama
Department of Gastroenterology, Takarazuka City Hospital, Takarazuka, Hyogo, Japan
Search for more papers by this authorFujimasa Tada
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
Search for more papers by this authorKazuhiro Nouso
Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
Search for more papers by this authorAsahiro Morishita
Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan
Search for more papers by this authorAkemi Tsutsui
Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorTakuya Nagano
Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorNorio Itokawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorTomomi Okubo
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorTaeang Arai
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorTakashi Nishimura
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorMichitaka Imai
Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
Search for more papers by this authorHisashi Kosaka
Department of Surgery, Kansai Medical University, Osaka, Japan
Search for more papers by this authorAtsushi Naganuma
Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
Search for more papers by this authorTomoko Aoki
Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
Search for more papers by this authorHidekatsu Kuroda
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
Search for more papers by this authorYutaka Yata
Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan
Search for more papers by this authorYoshiko Nakamura
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorOsamu Yoshida
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorShinichiro Nakamura
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
Search for more papers by this authorHirayuki Enomoto
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorMasaki Kaibori
Department of Surgery, Kansai Medical University, Osaka, Japan
Search for more papers by this authorYoichi Hiasa
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorMasatoshi Kudo
Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
Search for more papers by this authorthe Real-life Practice Experts for HCC (RELPEC) Study Group
Search for more papers by this authorthe Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group
Search for more papers by this authorTomomitsu Matono
Department of Gastroenterology, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Hyogo, Japan
Search for more papers by this authorCorresponding Author
Toshifumi Tada
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
Correspondence:
Toshifumi Tada ([email protected])
Search for more papers by this authorTakashi Kumada
Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
Search for more papers by this authorAtsushi Hiraoka
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
Search for more papers by this authorMasashi Hirooka
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorKazuya Kariyama
Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
Search for more papers by this authorJoji Tani
Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan
Search for more papers by this authorMasanori Atsukawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorKoichi Takaguchi
Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorEi Itobayashi
Department of Gastroenterology, Asahi General Hospital, Chiba, Japan
Search for more papers by this authorShinya Fukunishi
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorHiroki Nishikawa
Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan
Search for more papers by this authorKazunari Tanaka
Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan
Search for more papers by this authorKunihiko Tsuji
Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan
Search for more papers by this authorToru Ishikawa
Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
Search for more papers by this authorKazuto Tajiri
Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorYuichi Koshiyama
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
Search for more papers by this authorHidenori Toyoda
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
Search for more papers by this authorChikara Ogawa
Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorTakeshi Hatanaka
Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan
Search for more papers by this authorSatoru Kakizaki
Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
Search for more papers by this authorKazuhito Kawata
Department of Hepatology, Hamamatsu University School of Medicine, Shizuoka, Japan
Search for more papers by this authorHideko Ohama
Department of Gastroenterology, Takarazuka City Hospital, Takarazuka, Hyogo, Japan
Search for more papers by this authorFujimasa Tada
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
Search for more papers by this authorKazuhiro Nouso
Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
Search for more papers by this authorAsahiro Morishita
Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan
Search for more papers by this authorAkemi Tsutsui
Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorTakuya Nagano
Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
Search for more papers by this authorNorio Itokawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorTomomi Okubo
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorTaeang Arai
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Search for more papers by this authorTakashi Nishimura
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorMichitaka Imai
Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
Search for more papers by this authorHisashi Kosaka
Department of Surgery, Kansai Medical University, Osaka, Japan
Search for more papers by this authorAtsushi Naganuma
Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
Search for more papers by this authorTomoko Aoki
Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
Search for more papers by this authorHidekatsu Kuroda
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
Search for more papers by this authorYutaka Yata
Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan
Search for more papers by this authorYoshiko Nakamura
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorOsamu Yoshida
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorShinichiro Nakamura
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
Search for more papers by this authorHirayuki Enomoto
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorMasaki Kaibori
Department of Surgery, Kansai Medical University, Osaka, Japan
Search for more papers by this authorYoichi Hiasa
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan
Search for more papers by this authorMasatoshi Kudo
Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan
Search for more papers by this authorthe Real-life Practice Experts for HCC (RELPEC) Study Group
Search for more papers by this authorthe Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group
Search for more papers by this authorFunding: The authors received no specific funding for this work.
ABSTRACT
Background and Aim
To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).
Methods
A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS). We defined PD-multiple as the presence of two or more PD categories. Subsequent analysis was categorized into the “PD-IH or PD-EHS” and “PD-MVI or PD-multiple” groups.
Results
The median progression-free survival (PFS) durations for patients with PD-IH, PD-MVI, PD-EHS, and PD-multiple were 5.3, 3.2, 3.9, and 3.5 months (p = 0.003). Patients with “PD-IH or PD-EHS” and “PD-MVI or PD-multiple” had median PFS of 5.2 and 3.5 months (p < 0.001). Median overall survival (OS) for PD-IH, PD-MVI, PD-EHS, and PD-multiple was 22.3, 15.1, 19.4, and 14.2 months (p = 0.002). The OS for patients with “PD-IH or PD-EHS” and “PD-MVI or PD-multiple” was 21.4 and 14.5 months (p < 0.001). Multivariate analysis demonstrated that ECOG-PS ≥ 1 (hazard ratio (HR), 1.508), α-fetoprotein levels ≥ 100 ng/mL (HR, 1.293), albumin–bilirubin grade ≥ 2 (HR, 1.573), liver cirrhosis (HR, 1.361), and PD subtypes PD-MVI or PD-multiple (HR, 1.735) were independently associated with OS.
Conclusions
Patients with HCC undergoing Atezo/Bev treatment, diagnosed with PD-multiple (not solely based on IH or EHS) or PD-MVI, experienced poor prognosis, specifically in terms of OS.
Graphical Abstract
Conflicts of Interest
Toshifumi Tada: lecture fees from AbbVie, Eisai, and Chugai. Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka. Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer. Takeshi Hatanaka: lecture fees from Eisai. Masatoshi Kudo: advisory role at Eisai, Ono, MSD, Bristol-Myers Squibb, and Roche; lecture fees from Eisai, Bayer, MSD, Bristol-Myers Squibb, Eli Lilly, and EA Pharma; and research funding from Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, EA Pharma, AbbVie, and Eisai. None of the other authors have potential conflicts of interest to declare. Toshifumi Tada, Masanori Atsukawa, Hidekatsu Kuroda, and Masaki Kaibori are Editorial Board Members of Hepatology Research.
Open Research
Data Availability Statement
The datasets are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| jgh16884-sup-0001-Suppl_fig1.pdfPDF document, 19.3 KB |
Figure S1 Cumulative PPS curves categorized by the two additional PD subtypes. |
| jgh16884-sup-0002-Suppl_table1.pdfPDF document, 81.7 KB |
Table S1 Therapeutic responses (n = 462). |
| jgh16884-sup-0003-Suppl_table_2.pdfPDF document, 134 KB |
Table S2 Patient characteristics by PD subtypes (n = 462). |
| jgh16884-sup-0004-Suppl_table_3.pdfPDF document, 117.8 KB |
Table S3 p values for multiple comparisons using PD subtypes. |
| jgh16884-sup-0005-Suppl_text1.pdfPDF document, 105.1 KB |
Text S1 Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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