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

Abstract

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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 20 Pg. 5586-5594 (10 15 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 33926918 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Circulating Tumor DNA

Topics

• Adult
• Aged
• Aged, 80 and over
• Circulating Tumor DNA (blood)
• Colorectal Neoplasms (blood, pathology, surgery)
• Female
• Hematologic Tests
• Humans
• Male
• Middle Aged
• Neoplasm, Residual (blood)
• Prospective Studies