Evidence map›Paper›PMID 40055288›Full record

ArticleJournal of gastroenterology2025

Proposal of discontinuation criteria of atezolizumab plus bevacizumab after curative conversion therapy for unresectable early-to-intermediate-stage hepatocellular carcinoma: a multicenter proof-of-concept study.

Tomoko Aoki, Masatoshi Kudo, Naoshi Nishida, Kazuomi Ueshima, Kaoru Tsuchiya, Toshifumi Tada, Masahiro Morita, Hirokazu Chishina, Masahiro Takita, Satoru Hagiwara and 19 more

Abstract readMulticenter Study
In one paragraph

Article in Journal of gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  7. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Tomoko AokiDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.ORCID 0000-0002-9950-4553
Masatoshi KudoDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan. m-kudo@med.kindai.ac.jp.ORCID 0000-0002-4102-3474
Naoshi NishidaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.ORCID 0000-0002-9111-5668
Kazuomi UeshimaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.ORCID 0000-0002-7577-5789
Kaoru TsuchiyaDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Toshifumi TadaDepartment of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.ORCID 0000-0002-0976-6761
Masahiro MoritaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
Hirokazu ChishinaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
Masahiro TakitaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
Satoru HagiwaraDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
Hiroshi IdaDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
Yasunori MinamiDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.ORCID 0000-0001-7146-5954
Hidekatsu KurodaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan.ORCID 0000-0002-1471-1087
Noriaki NakamuraDepartment of General Surgery, Shuuwa General Hospital, Saitama, Japan.
Atsushi HiraokaGastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.ORCID 0000-0003-1989-0480
Tetsu TomonariDepartment of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.ORCID 0000-0002-8484-9866
Joji TaniDepartment of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
Atsushi NaganumaDepartment of Gastroenterology, NHO Takasaki General Medical Center, Takasaki, Japan.ORCID 0000-0003-0663-0102
Satoru KakizakiDepartment of Clinical Research, NHO Takasaki General Medical Center, Takasaki, Japan.ORCID 0000-0003-0224-7093
Chikara OgawaDepartment of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan.ORCID 0000-0002-4534-6692
Takeshi HatanakaDepartment of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.ORCID 0000-0003-3656-285X
Toru IshikawaDepartment of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.ORCID 0000-0002-5470-9694
Kazuhito KawataHepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.ORCID 0000-0002-4986-8578
Atsushi TakebeDepartment of Surgery, Kindai University Faculty of Medicine, Osaka, Japan.
Ippei MatsumotoDepartment of Surgery, Kindai University Faculty of Medicine, Osaka, Japan.ORCID 0000-0003-3965-3693
Masaaki HidakaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Masayuki KurosakiDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.ORCID 0000-0001-7016-8931
Takashi KumadaDepartment of Nursing, Gifu Kyoritsu University, Ogaki, Japan.ORCID 0000-0003-2211-495X
Namiki IzumiDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.ORCID 0000-0002-0055-8229

Funding

Japan Society for the Promotion of Science 21K07184Japan Society for the Promotion of Science 24K10393
6 · The paper itself

Abstract

backgroundAchieving complete response (CR) is a desirable goal in early-to-intermediate-stage hepatocellular carcinoma (HCC). While systemic and locoregional therapies show promise, optimal drug discontinuation criteria remain unclear. This study aims to investigate drug-off criteria for atezolizumab plus bevacizumab as a proof-of-concept study.

methodsThis retrospective multicenter study included child-pugh class A patients with unresectable HCC without extrahepatic spread or macrovascular invasion who received atezolizumab plus bevacizumab as first-line therapy. Modified clinical CR (mCCR) was defined as CR per mRECIST with sustained normal alpha-fetoprotein (AFP) levels (< 10.0 ng/dl). Recurrence-free survival (RFS) and overall survival (OS) were analyzed based on the "drug-off" criteria defined by following: (1) mRECIST CR with locoregional therapies, (2) sustained normalization of AFP/AFP-L3/ des-gamma-carboxy prothrombin (DCP) for 12-24 weeks, and (3) complete tumor vascularity disappearance by contrast-enhanced ultrasonography (CEUS) or pathological curative resection.

resultsThe median follow-up was 16.5 months (95% CI 15.2-17.8). Among 51 patients achieving mCCR, 11 underwent surgery, with pathological CR in three cases. In contrast, viable lesions were observed in 7 of 40 cases assessed using CEUS. All patients meeting the drug-off criteria (n = 9) showed no recurrence and none of them experienced mortality, while 45.2% (19/42) of those not meeting the criteria experienced recurrence (median RFS: 12.8 months, p = 0.007). The median OS was not reached in dug-off criteria met patients (n = 9), 37.7 months (95% CI: NA) in non-criteria met patients (n = 42), and 27.1 months (95% CI 16.7-37.6) in non-mCCR patients (n = 184) (p < 0.001).

conclusionIn patients with unresectable and TACE-unsuitable early-to-intermediate-stage HCC who met the drug-off criteria, significantly improved RFS and OS were observed compared those who did not meet the criteria. However, further validation studies are required to confirm the utility of the criteria.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, HepatocellularLiver NeoplasmsAdultAgedalpha-FetoproteinsDisease-Free SurvivalFemaleHumansMaleMiddle AgedNeoplasm StagingProof of Concept StudyRetrospective Studiesalpha-FetoproteinsAntibodies, Monoclonal, HumanizedatezolizumabBevacizumabCarcinoma, Hepatocellular [MH]Conversion therapyDrug-offImmune checkpoint inhibitors [MH]Treatment outcome [MH]

Identifiers

PMID40055288
PMCPMC12095402

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