Abstract

Introduction: Circulating tumor DNA (ctDNA) derived from apoptotic tumor cells is rapidly emerging as a non-invasive biomarker to detect the presence of tumor at a molecular level and guide therapy. In this study, we present our experience with this novel marker in gastrointestinal malignancy (GIM) patients. Methods: We included all patients with GIM for whom ctDNA was ordered from January 2020 to July 2021 at our center. Patient demographics, tumor type, pathology, stage, and radiographic findings were collected. Descriptive statistics were employed to report findings. Results: We identified 62 GIM patients for whom ctDNA was ordered. Results for 6 patients were not reported due to insufficient tumor tissue. Of the 56 patients for whom ctDNA results were available, 46 (82%) had colorectal adenocarcinoma (CRC) and the rest had other GI malignancies. Of the overall cohort of 56 evaluable patients, 21 (37.5%) had metastatic disease. Imaging findings paralleled ctDNA levels and correlated with tumor burden in 30 patients (53.5%). In 13 patients (23.2%), undetectable CT DNA levels influenced decisions regarding systemic therapy in addition to acting as a surrogate for treatment response. We discontinued maintenance therapy in 5 metastatic CRC patients with negative ctDNA and imaging. These patients have been off treatment for > 12 months without evidence of recurrence. We also truncated or skipped adjuvant treatment in 6 Stage III CRC patients with negative ctDNA and imaging who had significant post-operative complications or were otherwise considered high risk for severe toxicity. In one CRC patient, ctDNA was found to be undetectable post neoadjuvant therapy which corroborated with pathological complete response on surgical pathology report. 5 patients (9.09 %) had false-negative results and 1 patient had falsely elevated levels. In 6 other patients, we could not draw significant conclusions due to the availability of only a single value. Conclusion: Our experience suggests that ctDNA is not only a sensitive tool to assess tumor burden, but can also help guide therapy in locally advanced and metastatic CRC patients. However, further prospective studies are needed to improve the accuracy of test results and integrate ctDNA in day-to-day clinical practice.

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