Abstract

Abstract Introduction: Liquid biopsy based on detection of circulating tumor DNA (circulating-tumor DNA, ctDNA) is finding new applications in clinical management of solid cancers. From the initial use as an alternative to classical tissue biopsy for investigation of molecuar profiles in prediction or resistance detection of targeted therapies the approach is now applied to monitoring of minimal residual disease (MRD). Patients with metastatic colorectal cancer undergoing liver resection are subject to standard post-operative surveillance based mainly on periodic CT or PET/CT imaging (complemented eventually by MR imaging). Some reports have previously demonstrated benefit from performing a ctDNA detection complimentary to standard imaging to improve follow-up efficiency. Methods: In this report we demonstrate use of our oncoMonitor™ ctDNA technology, based on detection of somatic mutations derived from tumor in patient plasma. Unlike various approaches targeting oncogenic hotspot mutants, this technology can trace virtually any somatic mutation found in any gene (e.g. a tumor supressor). The relatively simple approach is based on rapid scanning of 100 to 140bp target amplicons for presence of mutations revealed based on differential melting by high-resolution denaturing capillary electrophoresis (DCE). The detection sensitivity is 0.1% MAF. Patients: In our concordance study during which a total of 41 patients with metatatic colorectal cancer were followed for 3 years from metastasectomy. oncoMonitor™ tast was applied to evaluate ctDNA along with standard CT or PET/CT imaging and tumor markers (CEA/CA19-9). Results: A total of 23 recurrences were clinically confirmed during surveillance. All recurrences were detected by oncoMonitor™ (23/23, 100%), while at the same time only 17 instances were detected by CT or PET/CT imaging (17/23, 73.9%) and 16 by tumor markers CEA/CA19-9 (16/23, 69.6%). There were 2 patients after R0 resection with persistent ctDNA positivity who had recurrence within 6 months from surgery. Conclusions: oncoMonitor™ technology is suitable for quick and sensitive detection of ctDNA in plasma of patients with metatatic colorectal cancer after liver resection. Evaluation of ctDNA presence improves efficiency of post-operative surveillance. Supported by Czech Ministry of Health project no. 17-31909A. Citation Format: Marek Minarik, Barbora Belsanova, Renata Ptackova, Tereza Halkova, Filip Pazdirek, Jiri Pudil, Miroslav Levy, Jaromir Simsa, Jiri Hoch, Miroslav Ryska, Lubos Petruzelka, Lucie Benesova. Application of oncoMonitor™ ctDNA tracking technology for monitoring of therapy and early detection of recurrence in metastatic colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 724.

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