Evidence map›Paper›PMID 38963640›Full record

ArticleHepatology international2024

Clinical significance of circulating biomarkers of immune-checkpoint molecules with atezolizumab plus bevacizumab therapy in unresectable hepatocellular carcinoma.

Makoto Chuma, Haruki Uojima, Hidenori Toyoda, Atsushi Hiraoka, Yoshitake Arase, Masanori Atsukawa, Norio Itokawa, Tomomi Okubo, Toshifumi Tada, Kazushi Numata and 15 more

Abstract read
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Article in Hepatology international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–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.

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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

25 authors.

Makoto Chuma *Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan. chuma@yokohama-cu.ac.jp.ORCID http://orcid.org/0000-0002-0963-9172
Haruki UojimaDepartment of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Hidenori ToyodaDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
Atsushi HiraokaGastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
Yoshitake AraseDivision of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Masanori AtsukawaDivision of Gastroenterology, Department of Internal Medicine, Nippon Medical School Hospital, Tokyo, Japan.
Norio ItokawaDivision of Gastroenterology, Department of Internal Medicine, Nippon Medical School Hospital, Tokyo, Japan.
Tomomi OkuboDivision of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.
Toshifumi TadaDepartment of Gastroenterology, Himeji Red Cross Hospital, Himeji, Japan.
Kazushi NumataGastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan.
Manabu MorimotoHepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Makoto Sugimori *Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan.
Akito NozakiGastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan.
Shuichiro IwasakiDepartment of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Satoshi YasudaDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
Yuichi KoshiyamaDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
Yusuke MishimaDivision of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Kota TsuruyaDivision of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Chikako TokoroDivision of Gastroenterology, Saiseikai Yokohamashi-Nanbu Hospital, Yokohama, Japan.
Yuki MiuraGastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan.
Hisashi HidakaDepartment of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Takashi Kumada *Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
Chika KusanoDepartment of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Tatehiro KagawaDivision of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Shin MaedaDepartment of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe aims of this study were to identify clinically significant biomarkers of a response to atezolizumab plus bevacizumab (ATZ + BV) therapy and to develop target strategies against unresectable hepatocellular carcinoma (u-HCC).

methodWe first investigated the potential of circulating tumor DNA (ctDNA) to serve as a biomarker for predicting the therapeutic outcome in 24 u-HCC patients treated with ATZ + BV therapy. Next, we analyzed levels of immune-related cytokines in blood samples from 134 u-HCC patients who received ATZ + BV. For this, serum immune-related molecules or cancer-immune cycle-related molecules that have been reported in HCC patient sera, namely CD274, LAG-3, CCL2, 4, 5, CXCL1, 9, 10, 12, 13, CX3CL1, CCR5, IFNγ and IL-6, 8 were measured using enzyme-linked immunosorbent assay.

resultsMore than 1% of variant read frequency (VRF) mutations were found in TP53, APC, PIK3CA and VHL, although with no correlation with treatment response. Among the 15 cytokines evaluated, CXCL9 and LAG-3 levels were significantly different between patients with objective response (OR), stable disease (SD), and progressive disease (PD) following ATZ + BV treatment. Receiver-operating characteristic curve analyses of CXCL9 (cut-off value: 419.1 pg/ml) and LAG-3 (cut-off value: 3736.3 pg/ml) indicated areas of 0.779 and 0.697, respectively, for differentiating PD from non-PD and OR from non-OR. In multivariate analysis of progression-free survival (PFS) and overall survival (OS), high serum CXCL9 (hazard ratio (HR) and 95% confidence interval (CI): 0.412 (0.251-0.677) (p = 0.0005) for PFS and 0.252 (0.125-0.508) (p = 0.0001) for OS), and low serum LAG-3 (HR and 95% CI 0.419 (0.249-0.705) (p = 0.0011) for PFS and 0.294 (0.140-0.617) (p = 0.0012) for OS) were independent positive predictive factors.

conclusionAlthough, as far as we examined, no ctDNA mutations in blood were found to be related to ATZ + BV treatment efficacy, serum CXCL9 and LAG-3 levels, which are related to the cancer-immune cycle, were associated with treatment efficacy and could be predictive markers of the efficacy of ATZ + BV treatment in HCC patients.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorCarcinoma, HepatocellularCirculating Tumor DNALiver NeoplasmsLymphocyte Activation Gene 3 ProteinAdultAgedAntigens, CDB7-H1 AntigenChemokine CXCL9Clinical RelevanceCytokinesFemaleAntibodies, Monoclonal, HumanizedAntigens, CDatezolizumabB7-H1 AntigenBevacizumabBiomarkers, TumorCD274 protein, humanChemokine CXCL9Circulating Tumor DNACXCL9 protein, humanCytokinesImmune Checkpoint InhibitorsLag3 protein, humanLymphocyte Activation Gene 3 ProteinAtezolizumab plus bevacizumabCXCL9Hepatocellular carcinomaImmune-checkpoint inhibitorLAG-3

Identifiers

PMID38963640

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.