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COSMOS-CRC-01: Sensitivity and Specificity of a Serial, Cell-Free DNA Epigenomic Platform in Detecting MRD in Real Time

Yoshiaki Nakamura, MD, PhD, discusses how the COSMOS-CRC-01 study assessed the sensitivity and specificity of a cell-free DNA epigenomic assay in R0 stage II to III CRC, emphasizing the importance of monitoring minimal MRD to inform treatment decisions and the critical lead time between ctDNA positivity and radiographic disease recurrence.

1. Please examine the sensitivityand specificity of a cell-free DNA epigenomic assay in resected cases of R0 stage II to III CRC.

  • How does this vary by site of tumor recurrence?
  • Does post treatment specificity of surveillance sampling improve with longer follow-up for MRD?

2. How do the data from COSMOS-CRC-01 inform us of possible persistent or converted MRD positivity 12months or beyond resection or ACT for stage II to III CRC?

  • How can the ability to track and detect new or treatment-nonresponsive MRD guide our future therapeutic choices to optimize survival benefits among patients with stage II to III CRC?

3. What is the importance of lead time between plasma ctDNA positivity and radiographic disease recurrence?

4. Please elaborate on how serial detection of tumor methylation fragments with a tissue-free ctDNA assay can facilitate genotyping and guideclinical decisions for postoperative/post-ACT patients who are MRD positive with stage II to III CRC.

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