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. 2024 Mar 14;13(6):1684.
doi: 10.3390/jcm13061684.

Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management

Britney Niemann  1 , John Moise  2 , Michael Sestito  1 , Midhun Malla  3 , Kevin Train  1 , Douglas Murken  1 , Keri Mayers  1 , Emily Groves  1 , Mary Garland-Kledzik  1
Affiliations

Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management

Britney Niemann et al. J Clin Med. .

Abstract

Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration.

Keywords: circulating tumor DNA (ctDNA); colorectal cancer; neoadjuvant.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) ctDNA levels prior to neoadjuvant treatment initiation in patients with positive to negative ctDNA conversion (converters) and patients with persistently positive ctDNA in the neoadjuvant setting (nonconverters). (B) Treatment effect score as defined by the Modified Ryan scheme for tumor regression, 0—2 correlated to a complete to partial treatment response and 3 to a poor or absent response. (C) Recurrence-free survival after a median follow-up of 14.5 months in converters and nonconverters.
Figure 2
Figure 2
(A) Number of cycles patients received prior to positive to negative ctDNA conversion. Median number of cycles was 5. Converters were divided into two groups based on total number of neoadjuvant cycles received (≤5 cycles or ≥6 cycles). (B) Total number of neoadjuvant cycles converters received in converters. (C) Treatment effect scores of converters receiving ≤5 cycles or ≥6 cycles. (D) Recurrence-free survival of converters who received ≤5 cycles versus ≥6 cycles neoadjuvant cycles.
Figure 3
Figure 3
(A) Treatment effect score and (B) recurrence-free survival of converters who received additional neoadjuvant systemic therapy after positive to negative ctDNA conversion compared to those who did not.
Figure 4
Figure 4
Recurrence-free survival based on postoperative ctDNA value in (A) stage III and (B) stage IV colorectal cancer. (C) Stage III and IV recurrence-free survival curves together.
Figure 5
Figure 5
ctDNA levels at time of recurrence separated by original stage and site of recurrence.
See this image and copyright information in PMC

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