Circulating DNA in patients undergoing loco-regional treatment of colorectal cancer metastases: a systematic review and meta-analysis

Louise B Callesen; Tana Takacova; Julian Hamfjord; Florian Würschmidt; Karl J Oldhafer; Roland Brüning; Dirk Arnold; Karen-Lise G Spindler

doi:10.1177/17588359221133171

Circulating DNA in patients undergoing loco-regional treatment of colorectal cancer metastases: a systematic review and meta-analysis

Ther Adv Med Oncol. 2022 Nov 2:14:17588359221133171. doi: 10.1177/17588359221133171. eCollection 2022.

Authors

Louise B Callesen^{1

2}, Tana Takacova^{3

4}, Julian Hamfjord^{5

6

7}, Florian Würschmidt⁸, Karl J Oldhafer^{3

9

10}, Roland Brüning^{3

11}, Dirk Arnold^{3

4}, Karen-Lise G Spindler^{12

13

3}

Affiliations

¹ Department of Experimental Clinical Oncology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N 8200, Denmark.
² Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ Asklepios Tumorzentrum Hamburg, Hamburg, Germany.
⁴ Department of Oncology and Palliative Care with Sections Hematology and Rheumatology, AK Altona, Hamburg, Germany.
⁵ Department of Oncology, Oslo University Hospital, Oslo, Norway.
⁶ Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
⁷ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁸ Radiologische Allianz, Hamburg, Germany.
⁹ Department of Surgery, Division of Hepato-biliary and Pancreatic (HBP) Surgery, AK Barmbek, Hamburg, Germany.
¹⁰ Faculty of Medicine, Semmelweis University Budapest, Asklepios Campus Hamburg, Hamburg, Germany.
¹¹ Department of Radiology and Neuroradiology, AK Barmbek, Hamburg, Germany.
¹² Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
¹³ Institute of Clinical Medicine, Aarhus University, Aarhus Denmark.

Abstract

Background: Loco-regional treatment strategies of colorectal cancer (CRC) metastases are evolving, but biological markers that can benefit patients and assist physicians in clinical decisions are lacking. The primary objective of this systematic review and meta-analysis is to investigate the current knowledge on circulating DNA and its clinical utility in predicting outcomes in patients undergoing loco-regional treatment of CRC metastases.

Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted on March 22, 2022. We included studies on patients undergoing loco-regional treatment of CRC metastases reporting the predictive or prognostic value of circulating DNA in the blood. Hazard ratios (HR) were pooled in separate random-effects meta-analyses to investigate if pre- or post-ablation measurements of circulating DNA were associated with survival. The risk of bias was assessed according to the Quality in Prognosis Studies tool.

Results: Twenty-eight studies with 2868 patients were included, of which 16 studies were eligible for meta-analyses. As expected in this new research field, a majority of included studies (n = 21/28) had a high risk of bias in at least one domain. Circulating DNA above the cutoff in a plasma sample taken before loco-regional treatment was associated with a short recurrence-free survival [pooled HR = 2.8, 95% confidence interval (CI) 1.4-5.7, n = 162] and overall survival (pooled HR = 4.7, 95% CI 1.1-20.6, n = 105). Circulating DNA above the cutoff in a plasma sample taken after loco-regional treatment was associated with a short recurrence-free survival (pooled HR = 4.5, 95% CI 3.4-6.1, n = 569) and overall survival (pooled HR = 7.5, 95% CI 2.0-27.3, n = 161). There was limited data on the association between dynamics in circulating DNA and outcome.

Conclusions: Measurements of circulating DNA can be valuable when selecting and monitoring patients undergoing loco-regional treatment of CRC metastases. Studies designed to investigate the true clinical utility of circulating DNA in the context of various ablation modalities are warranted.The review has been registered at PROSPERO (ID: CRD42022320032).

Keywords: biomarker; cell-free DNA; circulating free DNA; circulating tumor DNA; loco-regional treatment; metastatic colorectal cancer.

Publication types

Review