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. 2024 Jun 29;16(13):2407.
doi: 10.3390/cancers16132407.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer

Conor D J O'Donnell  1 , Nikolas Naleid  2 , Teerada Siripoon  1   3 , Kevin G Zablonski  2 , Michael H Storandt  1 , Jennifer E Selfridge  4 , Christopher L Hallemeier  5 , Madison L Conces  4 , Krishan R Jethwa  5 , David L Bajor  4 , Cornelius A Thiels  6 , Susanne G Warner  6 , Patrick P Starlinger  6 , Thomas D Atwell  7 , Jessica L Mitchell  8 , Amit Mahipal  4 , Zhaohui Jin  8
Affiliations

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer

Conor D J O'Donnell et al. Cancers (Basel). .

Abstract

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

Keywords: ablation; chemotherapy; circulating tumor DNA; colorectal cancer; hepatectomy; oligometastatic disease; stereotactic body radiation therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Disease-free survival (DFS) following locoregional therapy for oligometastatic disease by post-intervention circulating tumor DNA (ctDNA) status. NA—not assessed/not reached.
Figure 2
Figure 2
Forest plot of multivariable analysis of prognostic factors for DFS following locoregional therapy for oligometastatic disease. Significance codes: * p < 0.05; *** p < 0.001.
Figure 3
Figure 3
Percentage of recurrences detected with ctDNA testing for minimal residual disease (MRD). Assessment of MRD was defined as MRD occurring more than 28 days prior to radiographic evidence of disease.
Figure 4
Figure 4
ctDNA dynamics pre- and post-locoregional therapy for oligometastatic disease in the cohort of patients that had ctDNA testing performed prior to locoregional therapy.
Figure 5
Figure 5
DFS following locoregional therapy for oligometastatic disease according to post-intervention systemic therapy status in (a) the whole cohort, (b) patients with positive ctDNA within an 8-week window post-intervention, and (c) patients with negative ctDNA within an 8-week window post-intervention.
Figure 5
Figure 5
DFS following locoregional therapy for oligometastatic disease according to post-intervention systemic therapy status in (a) the whole cohort, (b) patients with positive ctDNA within an 8-week window post-intervention, and (c) patients with negative ctDNA within an 8-week window post-intervention.
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