Synapse - Clinical utility and tissue concordance of circulating tumor DNA in pancreatic ductal adenocarcinoma

Clinical utility and tissue concordance of circulating tumor DNA in pancreatic ductal adenocarcinoma Journal Article

Authors:	Keane, F.; Saadat, L.; O'Connor, C. A.; Chou, J. F.; Bowman, A. S.; Xu, F.; Crowley, F.; Debnath, N.; Schoenfeld, J. D.; Singhal, A.; Moss, D.; Cowzer, D.; Harrold, E.; Park, W.; Varghese, A.; Balogun, F.; Yu, K. H.; Zervoudakis, A.; Capanu, M.; Berger, M. F.; Wei, A. C.; Brannon, A. R.; O'Reilly, E. M.
Article Title:	Clinical utility and tissue concordance of circulating tumor DNA in pancreatic ductal adenocarcinoma
Abstract:	Background The utility of circulating tumor DNA (ctDNA) in addressing challenges of molecular tissue profiling and complementing next-generation sequencing is undefined in pancreas ductal adenocarcinoma. The objective of this study was to assess ctDNA detection rates by stage, disease burden, and metastasis patterns; compare overall survival between ctDNA-positive and ctDNA-negative patients cases; and determine concordance between ctDNA and matched-tissue biopsies.Methods Patients with pancreas ductal adenocarcinoma who had undergone Next Generation Sequencing by the MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Evaluate Somatic Status) ctDNA assay between 2019 and 2022 were included. Clinical and survival data were abstracted from a prospectively maintained clinical database.Results A total of 414 patients with pancreas ductal adenocarcinoma: 28% stage I-II, 21% stage III, 51% stage IV. ctDNA detection was highest among patients with advanced disease: 75% stage IV, 38% stage III, 34% stage I-II disease. For stage IV, ctDNA was more frequently detected in patients with at least 2 organs involved vs with less than 2 organs involved (76% vs 38%, P = .025). Higher rates of ctDNA detection were observed in patients with liver metastases vs without (82% vs 52%, P < .001). In the untreated stage IV cohort (n = 120), median overall survival was 10 months for those with detectable ctDNA (95% CI = 6.9 to 14 months) vs 19 months (95% CI = 13 months to not reached) for those with undetectable ctDNA (P = .1). Concordance between ctDNA and matched tissue next-generation sequencing was lower in untreated stage I-III disease, but high for untreated stage IV pancreas ductal adenocarcinoma, including a critical success index of 93.1% of KRAS variants.Conclusion ctDNA is a promising tool in the detection of somatic variants in pancreas ductal adenocarcinoma. Concordance between ctDNA and tissue is high for patients with untreated metastatic disease, notably for detection of KRAS variants.
Keywords:	survival; lung-cancer; tracking; ctdna; molecular residual disease
Journal Title:	JNCI: Journal of the National Cancer Institute
Volume:	117
Issue:	9
ISSN:	0027-8874
Publisher:	Oxford University Press
Publication status:	Published
Date Published:	2025-09-01
Online Publication Date:	2025-06-13
Start Page:	1848
End Page:	1857
Language:	English
ACCESSION:	WOS:001548973600001
DOI:	10.1093/jnci/djaf139
PROVIDER:	wos
PMCID:	PMC12415951
PUBMED:	40511613
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Eileen O'Reilly -- Source: Wos