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Long-Term ctDNA Analyses Test Risk for Recurrence in Patients With CRC

According to data being presented at the virtual 2020 ASCO Annual Meeting, circulating tumor DNA (ctDNA) analyses conducted postsurgery in patients with colorectal cancer (CRC) can detect those with a high risk for recurrence with almost 100% specificity.

“The clinical utility of tracking ctDNA as a noninvasive biomarker for detecting minimal residual disease (MRD) and stratifying patients based on their risk of developing relapse has been well established in CRC,” wrote Noelia Tarazona, MD, Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Instituto de Salud Carlos III, CIBERONC, Spain, and colleagues.

Using a cohort of 193 patients with resected stage I to III CRC, Dr Tarazona et al conducted a prospective, multi-center study assessing the detection and longitudinal monitoring of ctDNA in CRC patients before and after surgery, during and after adjuvant chemotherapy.

A total of 1052 plasma samples were collected from the study participants at various timepoints with a median follow up of 21.6 months. Whole-exome sequencing was used to compare individual tumors with matched germline DNA, and somatic mutations were identified.

Recurrence-free survival (RFS) was calculated in patients stratified by ctDNA status after surgery and adjuvant chemotherapy using Cox regression.

Before surgery, ctDNA was detected in 166 (90%) of 185 patients. Among 152 patients who had their post-surgery ctDNA status evaluated before adjuvant chemotherapy was administered, 14 (9.2%) were MRD-positive; 11 (78.5%) of these patients eventually had disease relapse.

By contrast, 13 (10.1%) of 138 patients found to be MRD-negative had relapsed disease (hazard ratio [HR], 16.53; 95% CI, 7.19-38.02; P <.001). After receipt of adjuvant chemotherapy (n = 84) and definitive therapy (n = 139), longitudinal ctDNA-positive status was tied to HRs of 27.92 (95% CI, 9.16-85.11; P <.001) and 47.52 (95% CI, 17.34-130.3.; P <.001), respectively.

According to multivariable analysis, longitudinal ctDNA status was the only significant prognostic factor tied to RFS (HR, 53.19; 95% CI, 18.87-149.90; P <.001). In addition, MRD was detected via serial ctDNA analysis up to a median of 9.08 months before radiologic relapse with a sensitivity of 79.1% and specificity of 99%.

“Postoperative ctDNA analyses detect patients with high-risk of recurrence, with near 100% specificity,” Dr Tarazona and colleagues wrote.

“Early detection of MRD and longitudinal monitoring of ctDNA could guide treatment decisions. Intervention trials to assess the clinical benefit of ctDNA use are underway,” they concluded.—Hina M. Porcelli

Tarazona N, Henriksen TV, Carbonell-Asinset JA, al. Circulating tumor DNA to detect minimal residual disease, response to adjuvant therapy, and identify patients at high risk of recurrence in patients with stage I-III CRC. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 4009.