Clinicopathological factors associated with tumour‐specific mutation detection in plasma of patients with RAS‐mutated or BRAF‐mutated metastatic colorectal cancer

Abstract

Detection of tumour-specific circulating cell-free DNA in plasma (ctDNA) fails in a significant number of cases depending on the clinical context. The primary aim was to investigate clinicopathological factors associated with detection of ctDNA in patients with RAS-/BRAF-mutated metastatic colorectal cancer (mCRC) prior to first-line therapy. A secondary aim was to evaluate the prognostic impact of ctDNA compared to other biomarkers. Patients were included from the NORDIC-VII study (N = 253). ctDNA was sampled prior to treatment and analysed for hotspot tissue mutations Abbreviations: CA19-9, carbohydrate antigen 19-9; CEA, carcinoembryonic antigen; cfDNA, total circulating cell-free DNA; CI, confidence interval; ctDNA, tumour-specific circulating cell-free DNA; ddPCR, droplet digital polymerase chain reaction; HR, hazard ratio; IL-6, interleukin 6; MAF, minor allele frequency; mCRC, metastatic colorectal cancer; OR, odds ratio; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; SIR, systemic inflammatory response; SLD, sum of the longest diameter of target lesions measured according to RECIST 1.0 at baseline; ULN, upper limit of normal; VIF, variance inflation factor; WBC, white blood cell.Karen-Lise Garm Spindler and Elin H. Kure equally shared senior authorship.

Circulating DNA and frequency of colorectal cancer brain metastases in a presumed high-risk group

“…In the present study, we detected ctDNA in 12 of 22 patients with radiological evident disease, with the highest detection frequency among patients with widespread disease (≥ 2 metastatic sites), indicating that patients with widespread disease may have a higher level of ctDNA. We observed a tendency for a higher frequency of ctDNA detection in patients with liver metastases, suggesting that liver metastases have a higher shedding of ctDNA compared to metastases in other locations, e.g., lung metastases, which is in accordance with the existing literature 15 – 17 .…”

Circulating tumor DNA: Response Evaluation Criteria in Solid Tumors – can we RECIST? Focus on colorectal cancer

“…Shedding of ctDNA varies with the tissue of origin, for example, liver metastases leading to higher levels of ctDNA in the blood samples. 52 Consequently, there will be a high but not complete concordance between mutations detected in the tumor tissue and blood samples, and analysis of the most commonly detected mutations will thus provide a ctDNA measure in approximately 40–50% of cases 51 , but these will not provide the same degree of a reliable quantitative measure. The panel of detected mutations can be broadened by, for example, mass array technology, or targeted or multigene panel NGS-based ctDNA assays but this methodology needs further clarification with respect to precision.…”

“…Shedding of ctDNA varies with the tissue of origin, for example, liver metastases leading to higher levels of ctDNA in the blood samples. 52 Consequently, there will be a high but not complete concordance between mutations detected in the tumor tissue and blood samples, and analysis of the most commonly detected mutations will thus provide a ctDNA measure in…”

Recent Advances in Device Engineering and Computational Analysis for Characterization of Cell-Released Cancer Biomarkers

“…As ctDNA has a short half-life, the downstream analysis should be performed immediately after extraction [ 33 ], but there are many steps in the conventional methods requiring the handling of samples that raise the risk of contamination [ 102 ]. Hence, automation of this procedure inside the closed channels of microfluidic chips could minimize the risk of rare sample loss while reducing labor.…”