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. 2021 May 6;13(9):2231.
doi: 10.3390/cancers13092231.

Clinical Implication of Liquid Biopsy in Colorectal Cancer Patients Treated with Metastasectomy

Soohyeon Lee  1 , Young-Soo Park  2 , Won-Jin Chang  1 , Jung Yoon Choi  1 , Ahreum Lim  1 , Boyeon Kim  2 , Saet-Byeol Lee  2 , Jong-Won Lee  2 , Seon-Hahn Kim  3 , Jin Kim  3 , Jung-Myun Kwak  3 , Kyung-Chul Yoon  3 , Sung-Ho Lee  4 , Yeul Hong Kim  1   2
Affiliations

Clinical Implication of Liquid Biopsy in Colorectal Cancer Patients Treated with Metastasectomy

Soohyeon Lee et al. Cancers (Basel). .

Abstract

Background & aims: The application of circulating tumor DNA (ctDNA) has been studied for predicting recurrent disease after surgery and treatment response during systemic treatment. Metastasectomy can be curative for well-selected patients with metastatic colorectal cancer (mCRC). This prospective study investigated the ctDNA level before and after metastasectomy in patients with mCRC to explore its potential as a predictive biomarker.

Methods: We collected data on 98 metastasectomies for mCRC performed from March 2017 to February 2020. Somatic mutations in the primary and metastatic tumors were identified and tumor-informed ctDNAs were selected by ultra-deep targeted sequencing. Plasma samples were mandatorily collected before and 3-4 weeks after metastasectomy and serially, if patients agreed.

Results: Data on 67 of 98 metastasectomies (58 patients) meeting the criteria were collected. ctDNA was detected in 9 (29%) of 31 cases treated with upfront metastasectomy and in 7 (19.4%) of 36 cases treated with metastasectomy after upfront chemotherapy. The detection rate of ctDNA was higher in liver metastasis (p = 0.0045) and tumors measuring ≥1 cm (p = 0.0183). ctDNA was less likely to be detected if the response to chemotherapy was good. After metastasectomy, ctDNA was found in 4 (6%) cases with rapid progressive disease.

Conclusion: The biological factors affecting the ctDNA shedding from the tumor should be considered when applying ctDNA assays in a clinical setting. After metastasectomy for oligometastatic lesions in good responders of chemotherapy, most ctDNA was cleared or existed below the detection level. To assist clinical decision making after metastasectomy for mCRC using ctDNA, further studies for improving specific outcomes are needed.

Keywords: circulating tumor DNA; liquid biopsy; metastasectomy; metastatic colorectal cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Workflow of the exploratory prospective study.
Figure 2
Figure 2
VAF difference between tumor and plasma under various conditions. (a) Mean VAF difference between tumor and plasma; (b) VAF difference between tumor and plasma under metastatic organ; (c) VAF difference between tumor and plasma under neoaduvant chemotherapy response.
See this image and copyright information in PMC

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