BACKGROUNDOne of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a “liquid (re)biopsy” it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient’s body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIMTo confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTSAmong the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers.CONCLUSIONctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.

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INTRODUCTION: Patients in advanced stages of non-small cell lung carcinomas (NSCLC), who and unsuited for targeted biological therapy because of lack of actionable molecular predictors are frequently treated by anti-angiogenic therapy. The effectiveness of such therapy is primarily relying on imaging techniques including CT or hybrid PET/CT evaluating a combination of morphological factors (dimensions and volume) and, more recently, also functional parameters including the metabolic activity, tumor vascularization etc. The ability to track the course of the disease at the same time all of these parameters is prerequisite to enable timely monitoring and therapy change in case of an early detection of resistance. This study was aimed at utility of circulating-tumor DNA (ctDNA) as an tool for monitoring of therapy response. and assessment of phenotypic parameters of the tumor. PATIENTS AND METHODS: A total of 50 patients with confirmed Stage IV lung adenocarcinomas showing negativity on ALK, BRAF, EGFR, RET, ROS1 and MET predictors were prospectively enrolled into the study. Patients were treated under a standard protocol by a combination of paclitaxes/carboplatin/bevacizumab and followed by dual PET/CT. For each patient cytology tissue sample was subjected to test for a panel of somatic mutations. The found mutations were subsequently detected in ctDNA in plasma extracted from peripheral blood collected prior to therapy start and then in 1-month intervals during the therapy. The occurrence and quantity of ctDNA were correlated with the objective therapy response (RECIST) and to the functional imaging parameters of metabolic activity and vascularization. RESULTS: ctDNA was initially positive in 29 patients. ctDNA levels closely reflected the response to the therapy with complete or partial remission expressed as reduction or absence of ctDNA, while disease stabilization or progression signaled by persisting or increasing ctDNA levels. There was a borderline correlation between ctDNA and vascularization evaluated by dual PET/CT (p=0.055). CONCLUSION: In a subset of patients ctDNA can readily serve as a surrogate marker for semi-continuous monitoring of the effect of anti-angiogenic therapy. Work supported by Czech Ministry of Health project AZV 17-30748A. Citation Format: Marek Minarik, Martin Svaton, Barbora Belsanova, Anastasiya Semyakina, Jan Baxa, Ondrej Fiala, Milos Pesek, Lucie Benesova. Application of a serial liquid biopsy ctDNA assay for monitoring efficacy of anti-angiogenic lung cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 412.

Introduction: ctDNA liquid biopsy has been recognized as a useful approach to monitor effect of ongoing cancer treatment. The ctDNA dynamics is reflecting the overall tumor burden. Here we present a utility of a simple ctDNA assay for longitudinal monitoring of patients with advanced stages of colorectal cancer in conjunction with surgical treatment. Patients and Methods: In a prospective setting the disease course of a total of 121 patients in Stage III and IV of colorectal cancer was monitored by ctDNA. A panel of somatic mutations was initially screened in primary and/or metastatic tissue. The found mutations were then traced in ctDNA from plasma acquired before surgery and during the subsequent days and months. In a subgroup of rectal cancers ctDNA was also analyzed prior and during the neoadjuvant chemoradiotherapy. The ctDNA levels were then correlated to the clinical parameters such as surgical radicality, disease relapse or response to anticancer therapy.Results: A brief overview of the ctDNA data is shown in Table I. TABLE I:ctDNA status in patients monitored in this studyTime of plasma samplingctDNA negativectDNA positivesample not availableprior to surgery309102 - 7 days after surgery30 (56%)24 (44%)373 months after surgery18 (54%)15 (46%)216 - 9 months after surgery8 (42%)11 (58%)1412 - 14 months after surgery4 (31%)9 (69%)418 - 24 months after surgery2 (28%)5 (72%)6 A high correlation between the surgical radicality and appearance or absence of ctDNA after surgery was confirmed with 22 of 24 patients with R0 resection as ctDNA negative and 22 of 30 patients with R1/R2 resection as ctDNA positive. Of the 30 ctDNA-negative patients following surgery, 4 patients had ctDNA-detectable progression during the first 9 months and 12 during the next 14 months. At 4 occasions the ctDNA has outperformed CT imaging in detecting the progression. The anti-angiogenic therapy resulted in disappearance or decrease of ctDNA levels in 6 patients during the first month of treatment. In a subgroup of rectal cancers, neoadjuvant chemoradiotherapy resulted in rapid decrease of ctDNA already in the first week of administration. Conclusion: The ctDNA dynamics closely follows clinical course of disease and may serve as a useful biomarker in post-operative follow-up. (supported by AZV 15-27939A) Citation Format: Marek Minarik, Tereza Halkova, Anastasiya Semyakina, Barbora Belsanova, Jiri Pudil, Filip Pazdirek, Miroslav Levy, Jaromir Simsa, Miroslav Hoch, Miroslav Ryska, Lucie Benesova. Using a ctDNA liquid biopsy assay for post-surgical serial monitoring and early detection of disease progression in advanced colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 405.

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