The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy.

Humans Nivolumab Stomach Neoplasms / drug therapy Cell-Free Nucleic Acids / genetics Biomarkers, Tumor / genetics Progression-Free Survival Microsatellite Instability

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
06 04 2023
Historique:
received: 25 01 2023
accepted: 30 03 2023
medline: 10 4 2023
entrez: 6 4 2023
pubmed: 7 4 2023
Statut: epublish

Résumé

To assess the potential clinical utility of cell-free DNA (cfDNA)-based biomarkers for identifying gastric cancer (GC) patients who benefit from nivolumab. From 31 GC patients treated with nivolumab monotherapy (240 mg/body, Bi-weekly) in 3rd or later line setting, we prospectively collected blood samples at baseline and before the 3rd dose. We compared cfDNA-based molecular findings, including microsatellite instability (MSI) status, to tissue-based biomarkers. We assessed the clinical value of blood tumor mutation burden (bTMB) and copy number alterations (CNA) as well as the cfDNA dynamics. The concordance between deficient-MMR and cfDNA-based MSI-high was 100% (3/3). Patients with bTMB ≥ 6 mut/Mb had significantly better progression-free survival (PFS) and overall survival (OS); however, such significance disappeared when excluding MSI-High cases. The combination of bTMB and CNA positivity identified patients with survival benefit regardless of MSI status (both PFS and OS, P < 0.001), with the best survival in those with bTMB

Identifiants

DOI: 10.1038/s41598-023-32645-x PMID: 37024664 PMC: PMC10079661
pubmed: 37024664
doi: 10.1038/s41598-023-32645-x
pii: 10.1038/s41598-023-32645-x
pmc: PMC10079661
doi:

Substances chimiques

Nivolumab 31YO63LBSN
Cell-Free Nucleic Acids 0
Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5652

Informations de copyright

© 2023. The Author(s).

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Auteurs

Chiaki Inagaki (C)

Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.
Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.

Hisato Kawakami (H)

Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan. kawakami_h@med.kindai.ac.jp.
ORCID: 0000-0002-3280-4850

Daichi Maeda (D)

Department of Molecular and Cellular Pathology, Graduate School of Medicine, Kanazawa University, Kanazawa, 920-1192, Japan.

Daisuke Sakai (D)

Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.
Center for Cancer Genomics and Personalized Medicine, Osaka University Hospital, Suita, 565-0871, Japan.

Shinya Urakawa (S)

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.

Kentaro Nishida (K)

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.

Toshihiro Kudo (T)

Department of Medical Oncology, Osaka International Cancer Institute, Osaka, 541-8567, Japan.

Yuichiro Doki (Y)

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.

Hidetoshi Eguchi (H)

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.

Hisashi Wada (H)

Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.

Taroh Satoh (T)

Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.
Center for Cancer Genomics and Personalized Medicine, Osaka University Hospital, Suita, 565-0871, Japan.

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