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Meta-Analysis
. 2022 Aug;127(3):500-513.
doi: 10.1038/s41416-022-01816-4. Epub 2022 Apr 19.

Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis

Louise B Callesen #  1   2 , Julian Hamfjord #  3   4   5 , Anders K Boysen  6 , Niels Pallisgaard  7 , Tormod K Guren  3 , Elin H Kure  4   8 , Karen-Lise G Spindler  6   9
Affiliations
Meta-Analysis

Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis

Louise B Callesen et al. Br J Cancer. 2022 Aug.

Abstract

Background: We investigate the current knowledge on circulating tumour DNA (ctDNA) and its clinical utility in predicting outcomes in patients with metastatic colorectal cancer (mCRC).

Methods: PubMed, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched. Last search 16/12/2020. We included studies on patients with mCRC reporting the predictive or prognostic value of ctDNA. We performed separate random-effects meta-analyses to investigate if baseline ctDNA and early changes in ctDNA levels during treatment were associated with survival. The risk of bias was assessed according to the Quality in Prognosis Studies tool.

Results: Seventy-one studies were included with 6930 patients. Twenty-four studies were included in meta-analyses. High baseline ctDNA level was associated with short progression-free survival (PFS) (HR = 2.2; 95% CI 1.8-2.8; n = 509) and overall survival (OS) (HR = 2.4; 95% CI 1.9-3.1; n = 1336). A small or no early decrease in ctDNA levels during treatment was associated with short PFS (HR = 3.0; 95% CI 2.2-4.2; n = 479) and OS (HR = 2.8; 95% CI 2.1-3.9; n = 583). Results on clonal evolution and lead-time were inconsistent. A majority of included studies (n = 50/71) had high risk of bias in at least one domain.

Conclusions: Plasma ctDNA is a strong prognostic biomarker in mCRC. However, true clinical utility is lacking.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic overview of clinical applications of liquid biopsies in patients with metastatic colorectal cancer during systemic anti-cancer treatment.
PFS progression-free survival, OS overall survival, ctDNA circulating tumour DNA, RECIST Response Evaluation Criteria in Solid Tumors PR partial response, PD progressive disease.
Fig. 2
Fig. 2. PRISMA diagram and eligible studies by year of publication.
PRISMA flow diagram of the study selection process (a). Number of included studies by year of publication (b).
Fig. 3
Fig. 3. Assessment of risk of bias using QUIPS (Quality in Prognosis Studies) tool.
The authors’ judgements regarding each risk-of-bias item presented as pecentages across all included studies.
Fig. 4
Fig. 4. Forest plots of the association between ctDNA levels and survival.
Forest plots of the association between unfavorable baseline ctDNA levels and progression-free survival (a) and overall survival (b); between unfavorable early dynamics in ctDNA levels and progression-free survival (c) and overall survival (d); all under the random-effects model. Dotted lines indicate first-line studies. Studies are ordered according to publication year. PFS progression-free survival, OS overall survival, n number of patients included in the analysis, HR hazard ratio, CI confidence interval.
See this image and copyright information in PMC

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