American Association for Cancer Research
Browse

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

Download (4.12 MB)
journal contribution
posted on 2023-03-31, 22:47 authored by Aparna R. Parikh, Emily E. Van Seventer, Giulia Siravegna, Anna V. Hartwig, Ariel Jaimovich, Yupeng He, Katie Kanter, Madeleine G. Fish, Kathryn D. Fosbenner, Benchun Miao, Susannah Phillips, John H. Carmichael, Nihaarika Sharma, Joy Jarnagin, Islam Baiev, Yojan S. Shah, Isobel J. Fetter, Heather A. Shahzade, Jill N. Allen, Lawrence S. Blaszkowsky, Jeffrey W. Clark, Jon S. Dubois, Joseph W. Franses, Bruce J. Giantonio, Lipika Goyal, Samuel J. Klempner, Ryan D. Nipp, Eric J. Roeland, David P. Ryan, Colin D. Weekes, Jennifer Y. Wo, Theodore S. Hong, Liliana Bordeianou, Cristina R. Ferrone, Motaz Qadan, Hiroko Kunitake, David Berger, Rocco Ricciardi, James C. Cusack, Victoria M. Raymond, AmirAli Talasaz, Genevieve M. Boland, Ryan B. Corcoran

Supplementary Figures

Funding

NCI Gastrointestinal Cancer SPORE

Stand Up To Cancer Colorectal Dream Team Translational Research Grant

Conquer Cancer Foundation of ASCO Career Development Award

American Cancer Society Institutional Research Grant

History

ARTICLE ABSTRACT

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. A total of 252 prospective serial plasma specimens from 103 patients with colorectal cancer undergoing curative-intent surgery were analyzed and correlated with recurrence. 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%]. 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

Usage metrics

    Clinical Cancer Research

    Categories

    Keywords

    BiomarkersEarly detection biomarkersClinical-Stage ResearchGastrointestinal CancersColorectal cancer

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC