S333 How Reliable Is Circulating Tumor DNA in Detecting Disease Progression or Regression of Non-Colorectal Gastrointestinal Cancers

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Introduction: Circulating tumor DNA are short DNA sequences of tumor cells shed into the systemic circulation. Post-operative ctDNA positivity has been studied as a potential marker for disease recurrence, however, dynamic changes in its level and immediate correlation with imaging have not been well described. Methods: We conducted a retrospective study including adult patients with non-colorectal gastrointestinal (GI) cancer. We evaluated the correlation of ctDNA with imaging studies to detect disease progression or regression. Eighteen patients, with 33 ctDNA samples were included. Results: Out of the 18 patients, five had pancreatic, three each had hepatocellular and cholangiocarcinoma, two each had anal cancer and neuroendocrine tumor, and one each had gastric, small bowel, and GI malignancy of unknown primary. Among the patients, 50% were male, and the median age at diagnosis was 64 years. 72.2% of the patients had advanced disease (stage III/IV), and only 22.2% had a predisposing condition leading to malignancy. Our primary endpoint, the correlation of single positive ctDNA results with imaging showing either progression or residual disease, showed a sensitivity of 60% and specificity of 100%. Secondarily, serial ctDNA was analyzed in ten patients with at least two ctDNA test results. This revealed a sensitivity of 80% and specificity of 100% for up-trending ctDNA values to detect progression, down-trending to detect regression, and persistent negative results to detect the absence of disease. This calculated sensitivity was lower than our separate analysis of colorectal cancer, where the sensitivity of single and serial ctDNA was 84.8% and 92.9%, respectively. The specificity, however, was 100% in both cancer groups. The positive ctDNA results detected disease progression with a median lead-time of 44 days compared to imaging. Conclusion: Colorectal cancer is the most studied malignancy in regards to the use of circulating tumor DNA as a marker of tumor recurrence. Similar studies in non-colorectal GI cancers are lacking. However, limited studies have shown some promising results for the use of post-operative ctDNA. The test’s sensitivity in our study was inferior compared to colorectal cancer, but given high specificity and improvement in sensitivity with serial analysis, ctDNA can be a valid way to monitor disease progression or regression in non-colorectal GI cancers. Further clinical studies are required to prove its utility in the reliable detection of immediate changes in disease status.





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