Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer.

Autor:	Parikh AR; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Van Seventer EE; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Siravegna G; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Hartwig AV; Guardant Health, Inc, Redwood City, California., Jaimovich A; Guardant Health, Inc, Redwood City, California., He Y; Guardant Health, Inc, Redwood City, California., Kanter K; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Fish MG; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Fosbenner KD; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Miao B; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Phillips S; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Carmichael JH; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Sharma N; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Jarnagin J; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Baiev I; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Shah YS; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Fetter IJ; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Shahzade HA; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Allen JN; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Blaszkowsky LS; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Clark JW; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Dubois JS; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Franses JW; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Giantonio BJ; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Goyal L; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Klempner SJ; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Nipp RD; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Roeland EJ; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Ryan DP; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Weekes CD; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Wo JY; Department of Radiation Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Hong TS; Department of Radiation Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts., Bordeianou L; Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts., Ferrone CR; Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts., Qadan M; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Kunitake H; Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts., Berger D; Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts., Ricciardi R; Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts., Cusack JC; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Raymond VM; Guardant Health, Inc, Redwood City, California., Talasaz A; Guardant Health, Inc, Redwood City, California., Boland GM; Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts., Corcoran RB; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts. rbcorcoran@partners.org.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Oct 15; Vol. 27 (20), pp. 5586-5594. Date of Electronic Publication: 2021 Apr 29.
DOI:	10.1158/1078-0432.CCR-21-0410
Abstrakt:	Purpose: Detection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery can identify patients with minimal residual disease (MRD) who will ultimately recur. Most ctDNA MRD assays require tumor sequencing to identify tumor-derived mutations to facilitate ctDNA detection, requiring tumor and blood. We evaluated a plasma-only ctDNA assay integrating genomic and epigenomic cancer signatures to enable tumor-uninformed MRD detection. Experimental Design: A total of 252 prospective serial plasma specimens from 103 patients with colorectal cancer undergoing curative-intent surgery were analyzed and correlated with recurrence. Results: Of 103 patients, 84 [stage I (9.5%), II (23.8%), III (47.6%), IV (19%)] had evaluable plasma drawn after completion of definitive therapy, defined as surgery only ( n = 39) or completion of adjuvant therapy ( n = 45). In "landmark" plasma drawn 1-month (median, 31.5 days) after definitive therapy and >1 year follow-up, 15 patients had detectable ctDNA, and all 15 recurred [positive predictive value (PPV), 100%; HR, 11.28 ( P < 0.0001)]. Of 49 patients without detectable ctDNA at the landmark timepoint, 12 (24.5%) recurred. Landmark recurrence sensitivity and specificity were 55.6% and 100%. Incorporating serial longitudinal and surveillance (drawn within 4 months of recurrence) samples, sensitivity improved to 69% and 91%. Integrating epigenomic signatures increased sensitivity by 25%-36% versus genomic alterations alone. Notably, standard serum carcinoembryonic antigen levels did not predict recurrence [HR, 1.84 ( P = 0.18); PPV = 53.9%]. Conclusions: Plasma-only MRD detection demonstrated favorable sensitivity and specificity for recurrence, comparable with tumor-informed approaches. Integrating analysis of epigenomic and genomic alterations enhanced sensitivity. These findings support the potential clinical utility of plasma-only ctDNA MRD detection. See related commentary by Bent and Kopetz, p. 5449 . (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu