QS132 - Evaluating the Role of Circulating Tumor DNA in Predicting Response to Total Neoadjuvant Therapy in Rectal Cancer Patients

Sunday, May 11, 2025

4:00 PM – 4:03 PM PT

Location: Room 9, Upper Level

Quick Shot Presenter(s)

Jared T. Yee

Research Coordinator
Washington University in St. Louis School of Medicine
San Francisco, CA, United States

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This individual has no financial relationships with ineligible companies.

Author(s)

Ahmed A. Eltahir, MD MPHS

General Surgery Resident
Washington University School of Medicine
Washington University in St. Louis
St. Louis, MO, United States

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CZ

Catherine Zivanov, MD MPHS

General Surgery Resident
Washington University School of Medicine
St. Louis, Missouri, United States

Disclosure information not submitted.
Oluseye Oduyale, MD MPHS

General Surgery Resident
Washington University School of Medicine
Washington University School of Medicine in St. Louis
St. Louis, Missouri, United States

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NK

Nathan S. Kau, n/a

Medical Student
Washington University School of Medicine in St. Louis
St. Louis, Missouri, United States

Disclosure information not submitted.
AD

Austin R. Dosch, MD, PhD

Assistant Professor
University of Miami Miller School of Medicine
Miami, Florida, United States

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Steven Hunt, MD

Professor of Surgery
Washington University School of Medicine
St. Louis, Missouri, United States

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PW

Paul E. Wise, MD

Vice Chair for Education
Washington University in St. Louis
St. Louis, Missouri, United States

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Matthew Mutch, MD

Professor of Surgery
Washington University
Washington University School of Medicine
St Louis, Missouri, United States

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Senior Author(s)

WC

William C. Chapman, Jr., MD

Assistant Professor
Washington University School of Medicine
St. Louis, Missouri, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

All of the relevant financial relationships listed below have been mitigated.

Jared T. Yee: This individual has no financial relationships with ineligible companies.

Ahmed A. Eltahir, MD MPHS: This individual has no financial relationships with ineligible companies.

Oluseye Oduyale, MD MPHS: This individual has no financial relationships with ineligible companies.

Steven Hunt, MD: This individual has no financial relationships with ineligible companies.

Matthew Mutch, MD: This individual has no financial relationships with ineligible companies.

William C. Chapman, MD, Jr.: This individual has no financial relationships with ineligible companies.

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Purpose/Background: Circulating tumor DNA (ctDNA) testing has emerged as a novel technology with vast potential for the diagnosis, management, and surveillance of human cancers. In rectal cancer management, particularly after total neoadjuvant therapy (TNT), ctDNA testing may help identify residual disease and improve selection of appropriate patients for nonoperative management. However, the effectiveness and optimal timing of ctDNA within this paradigm remains uncertain. This study aims to evaluate the association of ctDNA results with rectal tumor response to neoadjuvant treatment.

Methods/Interventions: We performed a retrospective analysis of a prospectively maintained database of patients with rectal cancer who were diagnosed between January 2017 and April 2024 at a single NCI-designated cancer center. ctDNA tests included tumor-informed and tumor-naïve analyses performed by third-party services. We analyzed trends in ctDNA utilization and assessed associations between post-TNT ctDNA status and TNT response. Complete responders were defined as patients who achieved either a pathological or sustained clinical complete response. Incomplete responders included partial responders, non-responders, and those who experienced local regrowth after an initial complete response (median follow up was 174 Days, Interquartile range, IQR 154 – 292). Among patients who were managed nonoperatively, rates of distant metastasis were also assessed. Statistical analyses utilized Pearson’s χ² and Fisher’s Exact tests. Analysis was performed using R statistical software.

Results/Outcomes: Among 716 patients, 103 patients underwent ctDNA testing after completing TNT. ctDNA testing increased from 2% of patients in 2017 to over 40% in 2023, with steady growth annually. Testing was performed at a median of 263 days after their restaging date (IQR 112 – 548). ctDNA-positive patients had a significantly lower rate of complete response to TNT compared to ctDNA-negative patients (12.5% vs. 36.7%, p = 0.026; Figure 1). Positive and negative predictive values were 0.875 and 0.367, respectively. Distant metastases occurred more frequently in ctDNA-positive patients than in ctDNA-negative patients (34.8% vs. 12.9%; p < 0.01).

Conclusion/Discussion: The increasing use of ctDNA testing reflects its growing role in rectal cancer management. Positive ctDNA status shows a trend toward lower rates of complete response. Given that a negative ctDNA status was not high in predictive value, we believe that ctDNA falls in line with other tumor markers such as CEA: a negative value is inconclusive, but elevated ctDNA should raise suspicion. The high positive predictive value indicates that ctDNA status can be used to rule out more conservative options for patients with inconclusive MRI or endoscopy. Our data also suggests that ctDNA results may be difficult to interpret given the inability to differentiate local vs distant residual tumor. Ultimately, ctDNA testing should be used more often in the management of rectal cancer but its integration with other clinical assessments must be done cautiously and multimodally.