Vascular Invasion Within the Resectability Criteria Is a Prognostic Factor in Patients Treated With Atezolizumab and Bevacizumab
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, Japan
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
Correspondence:
Toshifumi Tada ([email protected])
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, Toon, 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, Asahi, Chiba, Japan
Search for more papers by this authorShinya Fukunishi
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorHiroki Nishikawa
Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Takatsuki, 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, NHO 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
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, 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
Division of Gastroenterology and Hepatology, Department of Internal Medicine, 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, Hirakata, Osaka, Japan
Search for more papers by this authorAtsushi Naganuma
Department of Gastroenterology, NHO Takasaki General Medical Center, Takasaki, Gunma, Japan
Search for more papers by this authorTomoko Aoki
Department of Gastroenterology and Hepatology, Kindai University, Higashiosaka, Osaka, Japan
Search for more papers by this authorHidekatsu Kuroda
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba, Iwate, Japan
Search for more papers by this authorYutaka Yata
Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan
Search for more papers by this authorHideyuki Tamai
Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
Search for more papers by this authorTakanori Matsuura
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorShohei Komatsu
Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorYoshihide Ueda
Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Hyogo, Japan
Search for more papers by this authorYoshiko Nakamura
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Search for more papers by this authorOsamu Yoshida
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Search for more papers by this authorKosuke Matsui
Department of Surgery, Kansai Medical University, Hirakata, Osaka, 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
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorMasaki Kaibori
Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
Search for more papers by this authorTakumi Fukumoto
Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorYoichi Hiasa
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Search for more papers by this authorMasatoshi Kudo
Department of Gastroenterology and Hepatology, Kindai University, Higashiosaka, Osaka, Japan
Search for more papers by this authorthe Real-life Practice Experts for HCC (RELPEC) Study Group and the 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, Japan
Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
Correspondence:
Toshifumi Tada ([email protected])
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, Toon, 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, Asahi, Chiba, Japan
Search for more papers by this authorShinya Fukunishi
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorHiroki Nishikawa
Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Takatsuki, 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, NHO 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
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, 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
Division of Gastroenterology and Hepatology, Department of Internal Medicine, 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, Hirakata, Osaka, Japan
Search for more papers by this authorAtsushi Naganuma
Department of Gastroenterology, NHO Takasaki General Medical Center, Takasaki, Gunma, Japan
Search for more papers by this authorTomoko Aoki
Department of Gastroenterology and Hepatology, Kindai University, Higashiosaka, Osaka, Japan
Search for more papers by this authorHidekatsu Kuroda
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba, Iwate, Japan
Search for more papers by this authorYutaka Yata
Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan
Search for more papers by this authorHideyuki Tamai
Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
Search for more papers by this authorTakanori Matsuura
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorShohei Komatsu
Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorYoshihide Ueda
Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Hyogo, Japan
Search for more papers by this authorYoshiko Nakamura
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Search for more papers by this authorOsamu Yoshida
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Search for more papers by this authorKosuke Matsui
Department of Surgery, Kansai Medical University, Hirakata, Osaka, 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
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Japan
Search for more papers by this authorMasaki Kaibori
Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
Search for more papers by this authorTakumi Fukumoto
Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorYoichi Hiasa
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
Search for more papers by this authorMasatoshi Kudo
Department of Gastroenterology and Hepatology, Kindai University, Higashiosaka, Osaka, Japan
Search for more papers by this authorthe Real-life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 clinics in Japan (HCC 48) Group
Search for more papers by this authorHandling Editor: Alejandro Forner
Funding: The authors received no specific funding for this work.
ABSTRACT
Background and Aims
To assess the outcomes of patients with hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atezo/Bev), categorised by oncological resectability criteria, which reflect tumour burden and extent of disease.
Methods
A cohort of 467 HCC patients who received Atezo/Bev was enrolled. Patients were classified into two groups based on oncological resectability criteria: BR (borderline resectable) 1 (n = 153) and BR2 (n = 314).
Results
The median progression-free survival (PFS) was 9.0 months in the BR1 group and 6.8 months in the BR2 group (p = 0.014). Multivariable analysis identified the following independent prognostic factors for PFS: age ≥ 75 years (hazard ratio [HR], 1.309), albumin–bilirubin (ALBI) grade ≥ 2 (HR, 1.494), neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (HR, 1.289), α-fetoprotein ≥ 100 ng/mL (HR, 1.523) and BR2 classification (HR, 1.360). The median overall survival (OS) was 25.3 months in the BR1 group and 22.3 months in the BR2 group (p = 0.048). Multivariable analysis identified the following independent prognostic factors for OS: age ≥ 75 years (HR, 1.522), ALBI grade ≥ 2 (HR, 2.411), NLR ≥ 3 (HR, 1.635), α-fetoprotein ≥ 100 ng/mL (HR, 1.530) and BR2 classification (HR, 1.421). When oncological resectability factors (tumour number and size, vascular invasion and extrahepatic spread) were incorporated into the multivariable analysis, major vascular invasion emerged as a significant predictor of both PFS (HR, 3.188) and OS (HR, 2.650).
Conclusions
In patients with HCC characterised by limited resectability undergoing Atezo/Bev, vascular invasion, in addition to liver function, is a critical prognostic determinant of tumour progression.
Conflicts of Interest
Toshifumi Tada: lecture fees from AbbVie, AstraZeneca, 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. 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.
Open Research
Data Availability Statement
The datasets are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
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| liv70217-sup-0001-FigureS1.pdfPDF document, 23.5 KB |
Figure S1. |
| liv70217-sup-0002-TableS1-S4.pdfPDF document, 172.7 KB |
Tables S1–S4. |
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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