Validity and utility of blood tumor mutational burden (bTMB) is dependent on circulating tumor DNA (ctDNA) shed: SCRUM-Japan MONSTAR-SCREEN

Autor: Saori Mishima, Yoshiaki Nakamura, Hanna Tukachinsky, Hiroya Taniguchi, Shigenori Kadowaki, Ken Kato, Eiji Oki, Taroh Satoh, Daisuke Aoki, Kentaro Yamazaki, Taito Esaki, Makoto Ueno, Tomohiro Nishina, Yu Sunakawa, Tadamichi Denda, Hideaki Bando, Naomi Kuramoto, Satoshi Horasawa, Hikaru Abutani, Jessica K. Lee, Russell W. Madison, Geoffrey R. Oxnard, Takayuki Yoshino
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: The Journal of Liquid Biopsy, Vol 1, Iss , Pp 100003- (2023)
Druh dokumentu: article
ISSN: 2950-1954
DOI: 10.1016/j.jlb.2023.100003
Popis: Background: The tumor mutational burden (TMB) is a genomic biomarker associated with the benefits from immune checkpoint inhibitors (ICIs) cancer therapy. An elevated blood TMB (bTMB) in circulating tumor DNA (ctDNA) represents a compelling non-invasive diagnostic approach; however, the validity and utility of this emerging biomarker across cancer types have not been examined. Patient and methods: The blood and tissue TMB was measured in a large pan-tumor clinical cohort and the MONSTAR-SCREEN observational study (UMIN000036749) using the FoundationOne Liquid CDx and FoundationOne CDx assays. A subset of the MONSTAR-SCREEN cohort was used to evaluate the association between the bTMB and the efficacy of ICIs therapy. Results: The majority of cancer types showed similar prevalence of TMB≥10 mutations/megabase and bTMB≥10. There was high concordance between bTMB and TMB in blood and tissue biopsy from the same patient when the plasma tumor fraction (TF) was at least 1% (Spearman's coefficient 0.74 and > 80% sensitivity to detect TMB-high). High microsatellite instability (MSI-H) was detected by ctDNA with 79% sensitivity when TF was at least 1%, but only 6% sensitivity when TF was
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