Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

Abstract

The objective of this study was to characterize circulating tumor DNA (ctDNA) mutations in colorectal cancer (CRC) patients and evaluate their prognostic values during treatment. Forty-nine patients with CRC planned for operation were enrolled. A total of 115 plasma samples were collected pre-operation, post-operation, and post-chemotherapy. ctDNA analysis was performed using next-generation sequencing (NGS) including 14 genes. In 22 (44.9%) out of 49 patients, at least one mutation (40 total mutations) was detected in the initial plasma sample. The median sum of variant allele frequency was 0.74% (range: 0.10–29.57%). TP53 mutations were the most frequent (17 of 49 patients, 34.7%), followed by APC (18.4%), KRAS (12.2%), FBXW7 (8.2%), NRAS (2.0%), PIK3CA (2.0%), and SMAD4 (2.0%). After surgery, five (14.3%) out of 35 patients harbored ctDNA mutation. All five patients experienced relapse or metastasis during follow-up. It was noteworthy that all three patients with persistent ctDNA relapsed after R0 resection. After chemotherapy, ctDNA analysis was performed for 31 patients, all of which were ctDNA-negative. Analytical and clinical performances of NGS to utilize ctDNA in CRC were determined. Results revealed that postoperative ctDNA might serve as a marker for identifying risk of recurrence, thus contributing to patient-oriented treatment strategies.

Concordance of circulating tumor DNA and matched formalin-fixed paraffin-embedded tumor tissue in gastric cancer as a predictor of recurrence

“…In our study, preoperative positivity of tier II ctDNA variants was associated with a high cfDNA concentration, lymphatic invasion, and tumor N stage. These observations are in line with a previous report showing that advanced disease and lymph node involvement increase the likelihood of detectable preoperative ctDNA[ 15 ]; however, lymphatic invasion was unrelated to preoperative ctDNA positivity in other studies [ 16 , 17 ]. In our analysis of GC patients, preoperative ctDNA positivity was not associated with recurrence, as it was in patients with lung cancer [ 18 ], with the caveat that it likely correlated with advanced disease rather than simply predicted recurrence in the lung cancer patients [ 19 ].…”

Prognostic Factors for Localized Clear Cell Renal Cell Carcinoma and Their Application in Adjuvant Therapy

“…Elevated ctDNA levels may reveal disease recurrence/progression before radiologically detected disease progression and thus molecular residual disease is a compelling biomarker to monitor disease recurrence after radical surgery for the primary tumor. Detectable ctDNA (molecular residual disease) has been shown to predict disease recurrence after radical surgery for localized cancer in multiple tumor types, including melanoma [ 74 , 75 ], colorectal cancer [ 76 , 77 ], and NSCLC [ 78 , 79 ]. Interestingly, detectable plasma ctDNA was found to be a predictive biomarker for adjuvant atezolizumab therapy after surgery of urothelial carcinoma [ 80 ].…”