Journal
JOURNAL OF GASTROINTESTINAL ONCOLOGY
Volume 12, Issue 6, Pages 2643-2652Publisher
AME PUBLISHING COMPANY
DOI: 10.21037/jgo-21-484
Keywords
ctDNA; liquid biopsy; gastrointestinal malignancy; tumor informed
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This study utilized a personalized, tumor-informed ctDNA detection method in 198 GI cancer patients, showing that ctDNA positivity was significantly associated with advanced stage and presence/extent of metastases. Serial time-point analysis demonstrated successful clearance of ctDNA in a subset of patients following treatment.
Background: Gastrointestinal (GI) malignancies represent a heterogeneous group of diseases. Traditional tumor markers, though part of standard-of-care, lack sensitivity and specificity. Thmor-informed circulating tumor DNA (ctDNA) assay-based molecular residual disease assessment as well as recurrence and treatment response monitoring can serve as a robust tool in patients with wide range of GI malignancies and ethnicities. Methods: A personalized, tumor-informed multiplex PCR-NGS assay (Signatera (TM)) was used for the detection and quantification of ctDNA in 258 plasma samples from 198 patients with GI cancers at two institutions. Serial time- points were collected on a subset of patients (n=64) to monitor their ctDNA levels in response to treatment. Chi-square test was used to compare ctDNA-positivity rates in different cohorts. Results: The study included stage I-IV patients with a median age of 62 years (61% females and 49% ethnic minorities); 92% had surgical resection, 83% received systemic treatment. ctDNA-positivity was significantly associated with advanced stage (P=0.004), and presence/extent of metastases (P<0.00003). Serial time-point analysis showed that 22% (14/64) patients cleared ctDNA following treatment. ctDNA was detected in all patients who recurred (4/4; 100% sensitivity). Conclusions: Serial monitoring of ctDNA using a tumor-informed ctDNA assay can be prognostic and predictive in advanced GI malignancies in adjuvant setting.
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