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Circulating tumour DNA predicts recurrence in colorectal cancer

Presented by
Tenna Henriksen, Aarhus University, Denmark
Conference
ASCO GI 2021
Circulating tumour DNA (ctDNA) was analysed in plasma samples of colorectal cancer patients after surgery and adjuvant chemotherapy. Patients positive for ctDNA were shown to be at higher risk of recurrence, with ctDNA analysis being more predictive than standard CEA measurements. Furthermore, ctDNA analysis identified relapse 8 months earlier than radiologic examination.

PhD candidate Tenna Henriksen (Aarhus University, Denmark) presented the analysis of a promising novel biomarker in colorectal cancer patients [1]. There is a high relapse rate in colorectal cancer (CRC) despite curative intent treatment. To enhance recurrence risk assessment, ctDNA was assessed as a potential biomarker for minimal residual disease (MRD), which could help to detect recurrence early and thus increase patient survival. The aim of the presented study was to detect MRD, stratify patients into high and low risk of recurrence, assess post-therapy relapse risk in ctDNA-positive patients, and determine the lead time of ctDNA detection compared to radiological recurrence.

Serial postsurgical ctDNA assessment was performed in a prospective, multicentre study including 260 stage 1-3 CRC patients, who underwent tumour resection, of whom 166 were treated with adjuvant chemotherapy (ACT). Plasma samples were taken prior to surgery for baseline levels, and thereafter at 30 days and 3 months after surgery, and then every 3 months for 3 years, with a median follow-up time of 29.9 months in non-relapsed patients. Tumour recurrence was clinically assessed by computer tomography at 12 and 36 months after surgery. Individual tumours and matched germline DNA were whole-exome sequenced and somatic single nucleotide variants (SNVs) were identified. Personalised multiplex PCR assays were designed to track tumour-specific SNVs in each patient’s plasma sample.

Postoperative ctDNA status before ACT was assessed in 218 patients: 20/218 (9.17%) were MRD-positive, of whom 75% relapsed. The remaining 25% (5/20) of MRD-positive patients that did not relapse, received ACT. Of the MRD-negative patients, only 27/198 (13.6%) relapsed (HR 11; 95% CI 5.7-20; P<0.001). Post ACT-treatment, a ctDNA-positive status was associated with even higher relapse rates (HR 36; 95% CI 16-81; P<0.001).

To compare ctDNA assessment with standard of care carcinoembryonic antigen (CEA) measurements these were analysed in parallel. While single-time point CEA assessment post-surgery and post-ACT did not have a predictive power for recurrence-free survival, longitudinal CEA assessment was shown to have predictive power (HR 4.9; 95% CI 3.2-15; P<0.0001). Longitudinal ctDNA assessment, however, was significantly more predictive (HR 95.7; 95% CI 28-322; P<0.0001). In comparison with clinical CT evaluation, serial ctDNA analysis detected MRD markedly earlier in relapsing patients, with a median of 8 months (0.56-21.6 months).

In summary, postoperative ctDNA-positive status was associated with markedly reduced relapse-free survival. In a longitudinal setting, ctDNA analysis predicted the risk of recurrence and is a more reliable biomarker for treatment response monitoring.

  1. Henriksen T, et al. Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients. ASCO Gastrointestinal Cancers Symposium 2021, 15-17 January. Abstract 11.

 

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