Louise B Callesen1,2, Julian Hamfjord3,4,5, Anders K Boysen6, Niels Pallisgaard7, Tormod K Guren3, Elin H Kure4,8, Karen-Lise G Spindler6,9. 1. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. loucal@rm.dk. 2. Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. loucal@rm.dk. 3. Department of Oncology, Oslo University Hospital, Oslo, Norway. 4. Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. 5. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 6. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. 7. Department of Pathology, Zealand University Hospital, Roskilde, Denmark. 8. Department of Natural Sciences and Environmental Health, Faculty of Technology, Natural Sciences and Maritime Sciences, University of South-Eastern Norway, Campus Bø, Bø, Norway. 9. Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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.
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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