High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer

Bessa i Caserras, Xavier; Vidal Barrull, Joana; Balboa, J. C.; Márquez, Carmen; Duenwald, Sven J.; He, Y.; Raymond, Victoria M.; Faull, Iris; Burón, Andrea; Álvarez-Urturi, Cristina; Castells, Xavier; Bellosillo Paricio, Beatriz; Montagut Viladot, Clara

doi:http://dx.doi.org/10.1016/j.annonc.2023.09.3113

High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer

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Bessa X, Vidal J, Balboa JC, Márquez C, Duenwald S, He Y, Raymond V, Faull I, Burón A, Álvarez-Urturi C, Castells X, Bellosillo B, Montagut C. High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer. Ann Oncol. 2023 Dec;34(12):1187-93. DOI: 10.1016/j.annonc.2023.09.3113

Abstract

Background: Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness of colorectal cancer (CRC) screening. Patients and methods: A novel multimodal ctDNA-based blood assay that integrates genomics, epigenomics and fragmentomics, as well as proteomics in a refined version, was tested in blood samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals from the CRC Barcelona stool-based screening program; (ii) patients diagnosed with CRC. Primary endpoint was the performance of the test to detect CRC at different tumor-node-metastasis (TNM) stages. Secondary endpoint was the ability of the test to detect advanced precancerous lesions (advanced adenoma or advanced serrated lesion). Results: A total of 623 blood samples were analyzed in the primary analysis. Sensitivity and specificity of the assay to detect CRC was 93% and 90%, respectively. The sensitivity of CRC detection according to TNM stages was 84% for stage I, 94% for stage II and 96% for stage III (70/73) (P< 0.024). Sensitivity to detect advanced precancerous lesions was 23% with a refined version of the test (including protein and updating bioinformatic thresholding). Conclusion: A blood-based multimodal ctDNA assay detected CRC with high accuracy. This minimally invasive, accessible and convenient assay may help to increase the effectiveness of CRC screening.