Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer

Abstract

We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients ( = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2-335.5; < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5-15.7; = 0.007). Changes in ctDNA levels induced by relapse intervention ( = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman = 0.4). Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients. .

Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

“…The focus of these studies was on the correlation between variations in tumor volumes and in ctDNA between serial measurements. A significant correlation between differences in VAF and tumor volume was reported . Although the VAF shows a strong correlation with tumor volume in our study, it should be noted that there are still patients with high tumor volumes in whom no ctDNA was detected and vice versa .…”

“…Although some previous studies have correlated ctDNA to imaging findings (e.g., RECIST criteria or sum of target lesions), exact quantification of total 3D tumor volumes based on imaging has never been performed for PDAC . For other cancer types, a very small number of studies have correlated exact 3D‐measured tumor volume to ctDNA VAF (ovarian carcinoma, n = 40; colorectal cancer, n = 45) . The focus of these studies was on the correlation between variations in tumor volumes and in ctDNA between serial measurements.…”

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

“…Colorectal cancer (CRC) is one of the most common cancers worldwide and accounts for nearly 8.5% of total cancer mortality . Although the majority of primary tumors can be surgically resected, patients with late‐stage CRC suffer from a poor 5‐year survival rate, e.g., stage IV CRC patients account for less than 10% of the 5‐year survival rate . Tumor angiogenesis is essential for sustained tumor proliferation and distant metastasis .…”

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

“…Most studies focus on the presence of ccfDNA mutations in one or two genes to compare their presence to clinical outcome [19, 20]. In our study, we sought to assess the mutation patterns in a broad set of genes to highlight tumor heterogeneity and demonstrate clonal evolution over the course of disease progression.…”