TY - JOUR
T1 - White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer
AU - Leal, Alessandro
AU - van Grieken, Nicole C.T.
AU - Palsgrove, Doreen N.
AU - Phallen, Jillian
AU - Medina, Jamie E.
AU - Hruban, Carolyn
AU - Broeckaert, Mark A.M.
AU - Anagnostou, Valsamo
AU - Adleff, Vilmos
AU - Bruhm, Daniel C.
AU - Canzoniero, Jenna V.
AU - Fiksel, Jacob
AU - Nordsmark, Marianne
AU - Warmerdam, Fabienne A.R.M.
AU - Verheul, Henk M.W.
AU - van Spronsen, Dick Johan
AU - Beerepoot, Laurens V.
AU - Geenen, Maud M.
AU - Portielje, Johanneke E.A.
AU - Jansen, Edwin P.M.
AU - van Sandick, Johanna
AU - Meershoek-Klein Kranenbarg, Elma
AU - van Laarhoven, Hanneke W.M.
AU - van der Peet, Donald L.
AU - van de Velde, Cornelis J.H.
AU - Verheij, Marcel
AU - Fijneman, Remond
AU - Scharpf, Robert B.
AU - Meijer, Gerrit A.
AU - Cats, Annemieke
AU - Velculescu, Victor E.
N1 - Funding Information:
We thank all patients, treating physicians, and research support staff in all participating centers, the Netherlands Cancer Institute Trial Office for Safety Desk support and Monitoring, and the Central Datacenter of the Department of Surgery at the Leiden University Medical Center, Netherlands, for central data management. We thank members of our laboratories for critical review of the manuscript. This work was supported in part by the Stand Up to Cancer-Dutch Cancer Society International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1415), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Commonwealth Foundation, the Cigarette Restitution Fund, IASLC/Prevent Cancer Foundation, US National Institutes of Health grants CA121113, CA006973, CA233259, and CA193145, the Mark Foundation for Cancer Research, the V Foundation, the LUNGevity Foundation, Cancer Center Amsterdam grant CCA2015-5-24, and the Netherlands Organization for Health Research and Development (848101003). Central and local data management, on-site monitoring, and other costs of the CRITICS study were financially supported by a grant from the Dutch Cancer Society (CKTO 2006-02; NKI 2006-4167), Hoffman-La Roche, and the Dutch Colorectal Cancer Group. Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research.
Funding Information:
The authors declare the following competing interests: A.L., J.P., V. Adleff, and R.B.S. are founders of Delfi Diagnostics and own Delfi Diagnostics stock. V. Anagnostou receives research funding from Bristol-Myers Squibb. V.E.V. is a founder of Delfi Diagnostics and Personal Genome Diagnostics, a member of their Scientific Advisory Boards and Boards of Directors, and owns Delfi Diagnostics and Personal Genome Diagnostics stock, which are subject to certain restrictions under university policy. V.E.V. is an advisor to Bristol-Myers Squibb, Genentech, and Takeda Pharmaceuticals. Within the past 5 years, V.E.V. has been an advisor to Daiichi Sankyo, Janssen Diagnostics, and Ignyta. The terms of these arrangements are managed by Johns Hopkins University in accordance with its conflict of interest policies. The remaining authors declare no competing interests.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
AB - Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
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U2 - 10.1038/s41467-020-14310-3
DO - 10.1038/s41467-020-14310-3
M3 - Article
C2 - 31988276
AN - SCOPUS:85078362335
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 525
ER -