Abstract 717: Presence of distant metastases and disease progression but not tumor size, lymph node involvement, circadian rhythms, prior physical exercise or recent food consumption influence the concentration of circulating tumor DNA in cancer patients
Authors: Kuligina Ekaterina Sh , Meerovich Roman , Zagorodnev Kirill A. , Kholmatov Maxim M. , Laidus Tatiana A. , Martianov Aleksandr S. , Sokolova Tatyana N. , Anisimova Maria O. , Yanus Grigoriy A. , Imyanitov Evgeny N. 
Published: September 2020

Abstract
Liquid biopsy is potentially useful for early tumor detection, monitoring of cancer disease during treatment and diagnosis of therapy-related secondary mutations. Despite significant advantages, it cannot be routinely used in cancer medicine until the standardization of pre-analytical procedures is agreed. It is well known that the results of some blood-based diagnostic tests depend on the time of the day, prior fasting and recent physical exercise. We addressed the question whether these factors could influence the efficacy of the detection of actionable mutations in circulating tumor DNA (ctDNA). 437 plasma samples obtained from 88 patients (KRAS/NRAS/BRAF-mutated colorectal cancer (CRC): n= 57; EGFR-mutated lung adenocarcinomas (LC): n = 14; BRAF-mutated melanoma: n = 17) were analyzed by ddPCR for the presence of corresponding mutations in ctDNA. Patients provided their blood at 9 am (morning), at 1 pm (noon) and at 4 pm (afternoon). In addition, blood-takes were performed before and 15 minutes after the usual breakfast as well as before and 15 minutes after moderate physical exercise. Presence of tumor-specific mutations in plasma was confirmed in 32/57 (56%) CRC, 7/14 (50%) LC, and 4/17 (31%) melanoma cases. The amount of circulating mutant DNA did not correlate with the tumor size, presence of regional lymph node metastases or described above circumstances of blood-take. The proportion of mutation-positive plasma cases was significantly higher in the group of patients with distant metastases compared to subjects with localized disease [31/48 (65%) vs. 8/23 (35%), р = 0.023]. 48 patients were subjected to plasma analysis at the time of disease progression (PD), 37 individuals demonstrated disease control and 3 patients were in clinical remission with no radiologically detectable cancer lumps. Mutant gene copies were observed significantly more frequently in plasma specimens obtained from patients experiencing treatment failure [33/48 (68.8%) vs. 10/40 (25.0%), p = 0.00043]. The obtained data confirm the potential role of ctDNA testing for monitoring the course of cancer disease. The research is supported by RSF grant 18-75-10070.
Citation Format: Ekaterina Sh Kuligina, Roman Meerovich, Kirill A. Zagorodnev, Maxim M. Kholmatov, Tatiana A. Laidus, Aleksandr S. Martianov, Tatyana N. Sokolova, Maria O. Anisimova, Grigoriy A. Yanus, Evgeny N. Imyanitov. Presence of distant metastases and disease progression but not tumor size, lymph node involvement, circadian rhythms, prior physical exercise or recent food consumption influence the concentration of circulating tumor DNA in cancer patients [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 717.