Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy

作者：Sakti Chakrabarti, S. Marc Cohen, Antony Tin, Autumn Dangl, Ki Yong Chung, Mohamedtaki Abdulaziz Tejani, Marwan G. Fakih, Sreenivasa R Chandana, Colleen Donahue, Virgilio George, Midhun Malla, Vasily N. Aushev, Giby V. George, J. Bryce Ortiz, Whitney Herter, Arun Nagarajan, Benjamin A. Weinberg, Vivek R. Sharma, Gregory P. Botta, May Cho, Georges Azzi, Anup Kumar Kasi, F. Dayyani, Diana L. Hanna, Bradley G. Somer, Meenakshi Malhotra, Shruti Sharma, Adham Jurdi, Minetta C. Liu, R. Landmann, Arvind Dasari · 发表于：Cancers · 年份：2026 · DOI：10.3390/cancers18040589 · 被引用次数：1 · 研究领域：Cancer Genomics and Diagnostics、Cancer Cells and Metastasis、Genetic factors in colorectal cancer

Background: Circulating tumor (ct)DNA is a prognostic biomarker in gastrointestinal malignancies. In rectal cancer, its utility to inform perioperative management and predict recurrence, particularly in patients undergoing non-operative management (NOM), remains unclear. Studies are needed to clarify how post-neoadjuvant therapy (NAT) and post-surgical ctDNA status correlate with clinical outcomes in localized rectal cancer. Methods: We retrospectively analyzed ctDNA data from 220 patients with rectal cancer using a personalized tumor-informed assay (Signatera™, Natera, Inc., Austin, TX, USA). Of these, 148 (67.3%) underwent NAT followed by surgery, and 72 (32.7%) underwent NAT followed by NOM. We assessed associations between post-NAT ctDNA status and survival outcomes. In the surgical cohort, we examined associations between post-operative ctDNA status and clinical response, pathological response, survival outcomes, and NAR scores. Results: In the surgical cohort, ctDNA positivity at the post-operative MRD timepoint was a strong predictor of recurrence, with an 88.3% relapse rate compared to 11.5% in ctDNA-negative patients (p < 0.001). Among the 64 NOM patients with post-NAT ctDNA, 21.9% (14/64) were ctDNA-positive, of whom 100% (14/14) relapsed (92.9% local-only), 13 relapsed by the time of data cut-off, and one relapsed 8 months after the cut-off. Only 10% (5/50) of the ctDNA-negative NOM patients experienced local recurrence (p < 0.0001). ctDNA positivity post-NAT...