American Association for Cancer Research
Browse
ccr-21-2404_supps1.pdf (1.7 MB)

Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences

Download (1.7 MB)
journal contribution
posted on 2023-03-31, 23:02 authored by Tenna Vesterman Henriksen, Noelia Tarazona, Amanda Frydendahl, Thomas Reinert, Francisco Gimeno-Valiente, Juan Antonio Carbonell-Asins, Shruti Sharma, Derrick Renner, Dina Hafez, Desamparados Roda, Marisol Huerta, Susana Roselló, Anders Husted Madsen, Uffe S. Løve, Per Vadgaard Andersen, Ole Thorlacius-Ussing, Lene Hjerrild Iversen, Kåre Andersson Gotschalck, Himanshu Sethi, Alexey Aleshin, Andres Cervantes, Claus Lindbjerg Andersen
Supplementary Data from Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences

Funding

Novo Nordisk Foundation

Danish Cancer Society

Dansk Kræftforskningsfond

Krista and Viggo Petersen Foundation

Aarhus University

Instituto de Salud Carlos III

INCLIVA BioBank

Juan Rodés

Rio Hortega

History

ARTICLE ABSTRACT

Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates. We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples (n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing. Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7–13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4–167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9–172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1–6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography. Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making.See related commentary by Morris and George, p. 438

Usage metrics

    Clinical Cancer Research

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC