Whole-genome sequencing-based tumor-informed circulating tumor DNA monitoring for early detection of recurrence in patients with solid tumors
Abstract
Background: Circulating tumor DNA (ctDNA) assays can transform patient management by enabling molecular residual disease (MRD) detection, prognosis prediction, and treatment monitoring. Here, we report clinical performance of Signatera Genome, a whole-genome sequencing (WGS)-based ctDNA assay, in a diverse pan-cancer cohort at landmark and longitudinal settings post-definitive treatment.
Methods: We performed a retrospective analysis of 386 patients with one of the following cancers: breast, colorectal, non-small-cell lung, melanoma, or renal cell carcinoma. Signatera Genome assays, designed with high-quality variants selected from the matched tumor and normal WGS data, were used to detect ctDNA in the associated patients’ longitudinal plasma samples collected post-operatively. The correlation between ctDNA-based MRD status and systemic, distant recurrence-free survival (systemic DRFS) was assessed using Cox regression analysis.
Results: In the pan-cancer cohort, landmark analysis at 3 months post-surgery revealed that patients with MRD-positivity had significantly inferior systemic DRFS compared to ctDNA-negative patients (hazard ratio [HR]: 23.7, P < .0001). Additionally, ∼30% improvement in 24-month systemic DRFS was observed among adjuvant-treated MRD-positive patients, whereas MRD-negative patients derived no clear benefit from adjuvant therapy. In the longitudinal setting, MRD positivity anytime post-definitive treatment surveillance significantly correlated with shorter systemic DRFS compared to serial MRD negativity (HR: 103.4, P < .0001). Tumor-specific analyses yielded similar findings. Notably, 62% (72/116) of patients had ctDNA detected in the ultra-sensitive range of <100 ppm.
Conclusions: Our findings underscore the robust clinical performance of the Signatera Genome assay for MRD detection across solid tumors. Its broad applicability and high specificity support its integration into clinical practice and prospective trials.
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BibTeX
@article{george2026wholegenome,
title = {{Whole-genome sequencing-based tumor-informed circulating tumor DNA monitoring for early detection of recurrence in patients with solid tumors}},
author = {Mridula George and Gary S Schwartz and Wassim McHayleh and Vitaly Margulis and Hideaki Bando and Takayuki Yoshino and George Ansstas and Carly Bess Scalise and Sumedha Sudhaman and Arkarachai Fungtammasan and Bharat Sridhar and Jordan Feeney and Himanshu Sethi and Morgan M Quail and Sharlene Velichko and Wilson Tan and Alexander Hsieh and Anastasia Butskova and Ryan Ptashkin and Carcia Carson and Ashley Wray and Charuta C Palsuledesai and Meenakshi Malhotra and Ahmet Zehir and Eser Kirkizlar and Matthew Rabinowitz and Ryan K Swenerton and Gabrielle Heilek and Adham Jurdi and Adam C ElNaggar and Michael Krainock and Caitlin A Schonewolf and Angel A Rodriguez and Shruti Sharma and Ekaterina Kalashnikova and Minetta C Liu and Alexey Aleshin and Matthew D Galsky},
journal = {The Oncologist},
year = {2026},
month = oct,
doi = {10.1093/oncolo/oyag404},
url = {https://doi.org/10.1093/oncolo/oyag404},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Whole-genome sequencing-based tumor-informed circulating tumor DNA monitoring for early detection of recurrence in patients with solid tumors
AU - Mridula George
AU - Gary S Schwartz
AU - Wassim McHayleh
AU - Vitaly Margulis
AU - Hideaki Bando
AU - Takayuki Yoshino
AU - George Ansstas
AU - Carly Bess Scalise
AU - Sumedha Sudhaman
AU - Arkarachai Fungtammasan
AU - Bharat Sridhar
AU - Jordan Feeney
AU - Himanshu Sethi
AU - Morgan M Quail
AU - Sharlene Velichko
AU - Wilson Tan
AU - Alexander Hsieh
AU - Anastasia Butskova
AU - Ryan Ptashkin
AU - Carcia Carson
AU - Ashley Wray
AU - Charuta C Palsuledesai
AU - Meenakshi Malhotra
AU - Ahmet Zehir
AU - Eser Kirkizlar
AU - Matthew Rabinowitz
AU - Ryan K Swenerton
AU - Gabrielle Heilek
AU - Adham Jurdi
AU - Adam C ElNaggar
AU - Michael Krainock
AU - Caitlin A Schonewolf
AU - Angel A Rodriguez
AU - Shruti Sharma
AU - Ekaterina Kalashnikova
AU - Minetta C Liu
AU - Alexey Aleshin
AU - Matthew D Galsky
PY - 2026
DA - 2026/10/16
JO - The Oncologist
DO - 10.1093/oncolo/oyag404
UR - https://doi.org/10.1093/oncolo/oyag404
AB - Background: Circulating tumor DNA (ctDNA) assays can transform patient management by enabling molecular residual disease (MRD) detection, prognosis prediction, and treatment monitoring. Here, we report clinical performance of Signatera Genome, a whole-genome sequencing (WGS)-based ctDNA assay, in a diverse pan-cancer cohort at landmark and longitudinal settings post-definitive treatment. Methods: We performed a retrospective analysis of 386 patients with one of the following cancers: breast, colorectal, non-small-cell lung, melanoma, or renal cell carcinoma. Signatera Genome assays, designed with high-quality variants selected from the matched tumor and normal WGS data, were used to detect ctDNA in the associated patients’ longitudinal plasma samples collected post-operatively. The correlation between ctDNA-based MRD status and systemic, distant recurrence-free survival (systemic DRFS) was assessed using Cox regression analysis. Results: In the pan-cancer cohort, landmark analysis at 3 months post-surgery revealed that patients with MRD-positivity had significantly inferior systemic DRFS compared to ctDNA-negative patients (hazard ratio [HR]: 23.7, P < .0001). Additionally, ∼30% improvement in 24-month systemic DRFS was observed among adjuvant-treated MRD-positive patients, whereas MRD-negative patients derived no clear benefit from adjuvant therapy. In the longitudinal setting, MRD positivity anytime post-definitive treatment surveillance significantly correlated with shorter systemic DRFS compared to serial MRD negativity (HR: 103.4, P < .0001). Tumor-specific analyses yielded similar findings. Notably, 62% (72/116) of patients had ctDNA detected in the ultra-sensitive range of <100 ppm. Conclusions: Our findings underscore the robust clinical performance of the Signatera Genome assay for MRD detection across solid tumors. Its broad applicability and high specificity support its integration into clinical practice and prospective trials.
SN - 1083-7159
SN - 1549-490X
ER -