White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer

Alessandro Leal, Nicole C. T. van Grieken, Doreen N. Palsgrove, Jillian Phallen, Jamie E. Medina, Carolyn Hruban, Mark A. M. Broeckaert, Valsamo Anagnostou, Vilmos Adleff, Daniel C. Bruhm, Jenna V. Canzoniero, Jacob Fiksel, Marianne Nordsmark, Fabienne A. R. M. Warmerdam, Henk M. W. Verheul, Dick Johan van Spronsen, Laurens V. Beerepoot, Maud M. Geenen, Johanneke E. A. Portielje, Edwin P. M. Jansen, Johanna van Sandick, Elma Meershoek-Klein Kranenbarg, Hanneke W. M. van Laarhoven, Donald L. van der Peet, Cornelis J. H. van de Velde, Marcel Verheij, Remond Fijneman, Robert B. Scharpf, Gerrit A. Meijer, Annemieke Cats and Victor E. Velculescu ()
Additional contact information
Alessandro Leal: Johns Hopkins University School of Medicine
Nicole C. T. van Grieken: Vrije Universiteit
Doreen N. Palsgrove: Johns Hopkins University School of Medicine
Jillian Phallen: Johns Hopkins University School of Medicine
Jamie E. Medina: Johns Hopkins University School of Medicine
Carolyn Hruban: Johns Hopkins University School of Medicine
Mark A. M. Broeckaert: Vrije Universiteit
Valsamo Anagnostou: Johns Hopkins University School of Medicine
Vilmos Adleff: Johns Hopkins University School of Medicine
Daniel C. Bruhm: Johns Hopkins University School of Medicine
Jenna V. Canzoniero: Johns Hopkins University School of Medicine
Jacob Fiksel: Johns Hopkins University School of Medicine
Marianne Nordsmark: Aarhus University Hospital
Fabienne A. R. M. Warmerdam: Zuyderland Medical Centre
Henk M. W. Verheul: Vrije Universiteit
Dick Johan van Spronsen: Radboud University Nijmegen Medical Centre
Laurens V. Beerepoot: St. Elisabeth-Tweesteden Ziekenhuis
Maud M. Geenen: Onze Lieve Vrouwe Gasthuis
Johanneke E. A. Portielje: HAGA hospital
Edwin P. M. Jansen: Netherlands Cancer Institute
Johanna van Sandick: Netherlands Cancer Institute
Elma Meershoek-Klein Kranenbarg: Leiden University Medical Center
Hanneke W. M. van Laarhoven: Amsterdam UMC
Donald L. van der Peet: Vrije Universiteit
Cornelis J. H. van de Velde: Leiden University Medical Center
Marcel Verheij: Netherlands Cancer Institute
Remond Fijneman: Netherlands Cancer Institute
Robert B. Scharpf: Johns Hopkins University School of Medicine
Gerrit A. Meijer: Netherlands Cancer Institute
Annemieke Cats: Netherlands Cancer Institute
Victor E. Velculescu: Johns Hopkins University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-14310-3

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