Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy.
Simple Summary: Here, we evaluated whether circulating tumor DNA (ctDNA) measured after neoadjuvant therapy (NAT) or surgery can help to assess tumor response and predict recurrence risk in patients with locally advanced rectal cancer, including those managed non-operatively (NOM). In this large rea...
| Published in: | Cancers Vol. 18; no. 4; pp. 589 - 606 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | research tables/charts Journal Article |
| Published: |
MDPI
Feb2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191975603&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191975603 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Feb2026 vid: 18 iid: 4 pid: 97109 pub: MDPI artinfo: ui: 191975603 191975603 191975603 10.3390/cancers18040589 191975603 ppf: 589 ppct: 17 formats: tig: atl: Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy. aug: au: Chakrabarti, Sakti Cohen, Stacey A. Tin, Antony Dangl, Autumn Chung, Ki Y. Tejani, Mohamedtaki A. Fakih, Marwan G. Chandana, Sreenivasa R. Donahue, Colleen A. George, Virgilio Malla, Midhun Aushev, Vasily N. George, Giby V. Ortiz, J. Bryce Herter, Whitney K. Nagarajan, Arun Weinberg, Benjamin A. Sharma, Vivek R. Botta, Gregory P. Cho, May affil: University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA sug: subj: Rectal Neoplasms Therapy Rectal Neoplasms Surgery Rectal Neoplasms Prognosis Neoplasm Recurrence, Local Risk Factors Neoadjuvant Therapy Methods Cell-Free Nucleic Acids Blood Tumor Markers, Biological Blood Risk Assessment Human Female Male Adult Middle Age Aged Aged, 80 and Over Retrospective Design Record Review Biological Assay Cancer Patients Psychosocial Factors Prospective Studies Prediction Models Comparative Studies Polymerase Chain Reaction DNA Blood Rectal Neoplasms Familial and Genetic Kaplan-Meier Estimator Multivariate Analysis Cox Proportional Hazards Model Regression Descriptive Statistics Data Analysis Software Confidence Intervals Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Female Male ab: Simple Summary: Here, we evaluated whether circulating tumor DNA (ctDNA) measured after neoadjuvant therapy (NAT) or surgery can help to assess tumor response and predict recurrence risk in patients with locally advanced rectal cancer, including those managed non-operatively (NOM). In this large real-world study of 220 patients, ctDNA positivity after NAT or surgery was strongly correlated with recurrence risk. Among the NOM patients, post-NAT ctDNA positivity identified individuals at nearly universal risk of local regrowth, while ctDNA negativity predicted durable responses. In the surgical patients, ctDNA clearance after resection was associated with favorable outcomes. ctDNA provides a molecular measure of treatment response that complements radiographic and endoscopic assessment. These findings suggest that ctDNA may help to tailor local therapy and surveillance strategies in rectal cancer and warrant validation in prospective ctDNA-guided trials. 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 was associated with inferior DFS (p = 0.003). Conclusion: ctDNA was a strong predictor of recurrence in rectal cancer, including in NOM settings. In NOM patients, ctDNA detected local recurrences, highlighting its potential to guide post-NAT surveillance and treatment. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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