Longitudinal circulating tumor DNA monitoring in patients with esophageal squamous cell carcinoma.

person Shogo Takei Department of gastroenterology and gastrointestinal oncology, National Cancer Center Hospital East, Kashiwa, Japan info_outline Shogo Takei, Daisuke Kotani, Kazuma Sato, Naoto Fujiwara, Akihito Kawazoe, Shruti Sharma, Erik Spickard, Punashi Dutta, Minetta C. Liu, Adham A Jurdi, Kohei Shitara, Takashi Kojima, Takeo Fujita

Authors person Shogo Takei Department of gastroenterology and gastrointestinal oncology, National Cancer Center Hospital East, Kashiwa, Japan info_outline Shogo Takei, Daisuke Kotani, Kazuma Sato, Naoto Fujiwara, Akihito Kawazoe, Shruti Sharma, Erik Spickard, Punashi Dutta, Minetta C. Liu, Adham A Jurdi, Kohei Shitara, Takashi Kojima, Takeo Fujita Organizations Department of gastroenterology and gastrointestinal oncology, National Cancer Center Hospital East, Kashiwa, Japan, Division of Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan, Natera, Inc., Austin, TX, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan Abstract Disclosures Research Funding Institutional Funding Department of gastroenterology and gastrointestinal oncology, National Cancer Center Hospital East Background: The clinical utility of longitudinal monitoring with circulating tumor DNA (ctDNA) as a prognostic and a predictive biomarker was recently reported in patients with resectable colorectal cancer (Kotani D, et al. Nature Medicine 2023). Here we report a prospective, observational study of longitudinal ctDNA monitoring in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemotherapy (NAC) followed by surgery. Methods: Patients with ESCC planned for NAC followed by curative surgery, were prospectively enrolled in this study. As per the protocol, plasma samples were collected at 7 timepoints: pre-NAC, post-NAC, and 4,12, 24, 36, and 48-weeks after surgery. CT scans were conducted every 3 months. Longitudinal ctDNA testing was performed using a personalized, tumor-informed ctDNA assay (Signatera, bespoke mPCR, NGS assay). In this initial report, ctDNA results at 3 time points (pre-NAC, post-NAC, and 4 weeks post-surgery) were analyzed and their association with clinical outcomes and tumor regression grade (TRG) scores were assessed. Results: So far, a total of 83 blood samples from 28 patients with ESCC were collected serially at pre-NAC (N=28), post-NAC (N=27), and post-surgical (N=28) time points. Pre-NAC ctDNA was detectable in 96.4% patients (27/28), and detection rates decreased at the post-NAC (37%; 10/27) and post-surgical (11%; 3/28) timepoints. ctDNA-positivity post-NAC and post-surgery was associated with a significantly shorter recurrence free survival (RFS) with HR of 7.0 (95% CI: 1.4-35.0; p = 0.02) and HR of 14 (95% Cl 3.0-62; p <0.001), respectively. Notably, patients who achieved ctDNA clearance with NAC had favorable RFS as compared to the patients who did not (HR=0.15, 95% CI: 0.03 – 0.75; p = 0.02). Post-NAC ctDNA was also associated with tumor regression grade (TRG) score. None of the patients with TRG3 score (N=3) were ctDNA positive, whereas 7.7% (1/13) patients in the TRG2 category and 81.8% (9/11) in the TRG1 category were ctDNA-positive. Conclusions: Our study demonstrates a strong correlation between ctDNA status and clinical outcomes in ESCC patients. Assessment of ctDNA may be useful monitoring in patients with ESCC post NAC/surgery and may be used in the future to direct post-surgical management in this patient population. Clinical trial information: UMIN000042003.

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