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Related Experiment Video

Updated: Jul 6, 2025

Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
06:53

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Circulating Tumor DNA to Predict Radiographic and Pathologic Response to Total Neoadjuvant Therapy in Locally

Stephanie L Alden1, Valerie Lee2, Amol K Narang3

  • 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The Oncologist
|January 5, 2024
PubMed
Summary

Post-neoadjuvant therapy circulating tumor DNA (ctDNA) shows low sensitivity in predicting treatment response for locally advanced rectal cancer (LARC). Current ctDNA assays are insufficient alone for selecting patients for nonoperative management (NOM).

Keywords:
circulating tumor DNAnonoperative managementrectal cancertotal neoadjuvant therapy

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Surgical Oncology

Background:

  • Locally advanced rectal cancer (LARC) treatment has advanced, but patient selection for nonoperative management (NOM) remains challenging.
  • Accurate assessment of treatment response is crucial for optimizing LARC management strategies.

Purpose of the Study:

  • To evaluate the utility of post-total neoadjuvant therapy (TNT) circulating tumor DNA (ctDNA) in predicting treatment response in LARC patients.
  • To determine if ctDNA can reliably predict residual disease and tumor regression after TNT.

Main Methods:

  • Single-center, retrospective study.
  • Analysis of post-TNT ctDNA levels.
  • Correlation of ctDNA results with pathological residual disease and MRI-based tumor regression.

Main Results:

  • Post-TNT ctDNA demonstrated low sensitivity (23%) but high specificity (100%) for predicting residual disease, with a 100% PPV and 47% NPV.
  • For predicting poor tumor regression on MRI, ctDNA showed 16% sensitivity and 96% specificity, with a 75% PPV and 60% NPV.
  • A commercially available ctDNA assay was insufficient to predict residual disease post-TNT.

Conclusions:

  • Post-TNT ctDNA is not a reliable standalone biomarker for selecting LARC patients for NOM.
  • Further research is needed to develop more sensitive and specific biomarkers for treatment response assessment in LARC.