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

6533b7d2fe1ef96bd125e10f

RESEARCH PRODUCT

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

Lene Hjerrild Iversen Claus L. Andersen Derrick Renner Thomas Reinert Ole Thorlacius-ussing Desamparados Roda Tenna V Henriksen Alexey Aleshin Andrés Cervantes Noelia Tarazona Per Vadgaard Andersen Shruti Sharma Susana Roselló J.a. Carbonell-asins Dina Hafez Anders Husted Madsen Uffe S. Løve Kåre Andersson Gotschalck Amanda Frydendahl Marisol Huerta F. Gimeno-valiente Himanshu Sethi

subject

Male Oncology Cancer Research medicine.medical_specialty Neoplasm Residual Adjuvant chemotherapy Clinical Decision-Making Circulating Tumor DNA Text mining Predictive Value of Tests Internal medicine Biomarkers Tumor Stage III colorectal cancer medicine Adjuvant therapy Humans Tumor growth Aged Neoplasm Staging business.industry Prognosis Minimal residual disease Confidence interval Oncology Circulating tumor DNA Female Drug Monitoring Neoplasm Recurrence Local Colorectal Neoplasms business

description

Abstract Purpose: 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. Experimental Design: 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. Results: Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7–13.5; P &lt; 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4–167; P &lt; 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 &lt; 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P &lt; 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. Conclusions: 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

year	journal	country	edition	language
2022-02-01	Clinical Cancer Research

https://doi.org/10.1158/1078-0432.ccr-21-2404