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Timing of ctDNA Analysis Aimed at Guiding Adjuvant Treatment in Colorectal Cancer

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Title: Timing of ctDNA Analysis Aimed at Guiding Adjuvant Treatment in Colorectal Cancer
Authors: Tenna V. Henriksen, Christina Demuth, Amanda Frydendahl, Jesper Nors, Marijana Nesic, Mads H. Rasmussen, Ole H. Larsen, Claudia Jaensch, Uffe S. Løve, Per V. Andersen, Thomas Kolbro, Ole Thorlacius-Ussing, Alessio Monti, Jeppe Kildsig, Peter Bondeven, Nis H. Schlesinger, Lene H. Iversen, Kåre A. Gotschalck, Claus L. Andersen
Source: Henriksen, T V, Demuth, C, Frydendahl, A, Nors, J, Nesic, M, Rasmussen, M H, Larsen, O H, Jaensch, C, Løve, U S, Andersen, P V, Kolbro, T, Thorlacius-Ussing, O, Monti, A, Kildsig, J, Bondeven, P, Schlesinger, N H, Iversen, L H, Gotschalck, K A & Andersen, C L 2025, 'Timing of ctDNA Analysis Aimed at Guiding Adjuvant Treatment in Colorectal Cancer', Clinical Cancer Research, vol. 31, no. 9, pp. 1676-1685. https://doi.org/10.1158/1078-0432.CCR-24-3200
Publisher Information: American Association for Cancer Research (AACR), 2025.
Publication Year: 2025
Subject Terms: Male, Adult, Aged, 80 and over, Time Factors, Liquid Biopsy, Liquid Biopsy/methods, Middle Aged, Prognosis, Colorectal Neoplasms/genetics, Circulating Tumor DNA, Circulating Tumor DNA/blood, Chemotherapy, Adjuvant, Biomarkers, Tumor, Humans, Female, Biomarkers, Tumor/genetics, Colorectal Neoplasms, Chemotherapy, Adjuvant/methods, Aged, Neoplasm Staging
Description: Purpose: Multiple clinical trials are investigating ctDNA to guide adjuvant chemotherapy (ACT) in colorectal cancer. Timely ACT initiation necessitates early ctDNA testing, but the impact of postoperative cell-free DNA (cfDNA) and ctDNA dynamics remains unclear, particularly with cost-reducing input caps employed in some assays. This study investigates ctDNA detection at day 14 versus day 30, comparing whole-sample analysis with capping the cfDNA input, and evaluates single and dual timepoint assessments for ACT allocation. Experimental Design: From 2019 to 2023, 611 patients with stage I to III colorectal cancer were enrolled. Blood was collected preoperatively and postoperatively on ∼day 14 and ∼day 30. The cfDNA levels were assessed using digital PCR, and ctDNA was assessed using tumor-informed digital PCR or targeted sequencing analyzing all cfDNA from 8 mL of plasma. Results: Despite elevated cfDNA in 85% of day 14 samples, performance was comparable between the two timepoints (sensitivity, 31% vs. 32% and specificity, both 98%). A 50-ng cfDNA input cap reduced ctDNA detection probability, affecting 78% of day 14 samples and 65% of day 30 samples. At both timepoints, ctDNA detection was prognostic of recurrence (day 14; HR, 9.0, 95% confidence interval, 5.5–14.8 and day 30: HR, 12.5, 95% confidence interval, 7.6–20.4). In 74% of ctDNA-positive recurrence patients, both samples had ctDNA detected. An increase in the ctDNA level from day 14 to day 30 was associated with a shorter time to recurrence (Pearson R = −0.63, P = 0.003). Combining the timepoints would increase sensitivity (36%) and allow earlier ACT start in 80% of patients. Conclusions: Early ctDNA sampling is feasible and highly prognostic. Supplemental later testing may improve sensitivity while allowing early ACT initiation for most ctDNA-positive patients.
Document Type: Article
Language: English
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-24-3200
Access URL: https://pubmed.ncbi.nlm.nih.gov/39976513
Accession Number: edsair.doi.dedup.....7bf14108d302a6dfde48f70c36ae5ce6
Database: OpenAIRE
Description
Abstract:Purpose: Multiple clinical trials are investigating ctDNA to guide adjuvant chemotherapy (ACT) in colorectal cancer. Timely ACT initiation necessitates early ctDNA testing, but the impact of postoperative cell-free DNA (cfDNA) and ctDNA dynamics remains unclear, particularly with cost-reducing input caps employed in some assays. This study investigates ctDNA detection at day 14 versus day 30, comparing whole-sample analysis with capping the cfDNA input, and evaluates single and dual timepoint assessments for ACT allocation. Experimental Design: From 2019 to 2023, 611 patients with stage I to III colorectal cancer were enrolled. Blood was collected preoperatively and postoperatively on ∼day 14 and ∼day 30. The cfDNA levels were assessed using digital PCR, and ctDNA was assessed using tumor-informed digital PCR or targeted sequencing analyzing all cfDNA from 8 mL of plasma. Results: Despite elevated cfDNA in 85% of day 14 samples, performance was comparable between the two timepoints (sensitivity, 31% vs. 32% and specificity, both 98%). A 50-ng cfDNA input cap reduced ctDNA detection probability, affecting 78% of day 14 samples and 65% of day 30 samples. At both timepoints, ctDNA detection was prognostic of recurrence (day 14; HR, 9.0, 95% confidence interval, 5.5–14.8 and day 30: HR, 12.5, 95% confidence interval, 7.6–20.4). In 74% of ctDNA-positive recurrence patients, both samples had ctDNA detected. An increase in the ctDNA level from day 14 to day 30 was associated with a shorter time to recurrence (Pearson R = −0.63, P = 0.003). Combining the timepoints would increase sensitivity (36%) and allow earlier ACT start in 80% of patients. Conclusions: Early ctDNA sampling is feasible and highly prognostic. Supplemental later testing may improve sensitivity while allowing early ACT initiation for most ctDNA-positive patients.
ISSN:15573265
10780432
DOI:10.1158/1078-0432.ccr-24-3200