Abstract

There is a lack of convenient, sensitive, noninvasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating epithelial cells (CECs) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy. A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects undergoing colonoscopy) was conducted. The test analyzed CECs and somatic mutations. The probability of advanced neoplasia (advanced adenoma [AA] and CRCs) was determined by logistic regression methods adjusted for expected CRC incidence rate, prior history of AA, and patient age and sex on a training subset. A linear predictor was developed to generate a score scaled from 0 to 100. The test performance was evaluated on an independent set of subjects using prespecified algorithms and cut point. Based on a predefined clinical threshold and predictive model derived from the training set (n= 232), analysis of an independent asymptomatic validation set (n= 194) yielded 89% (lower exact one-sided 95% confidence interval [CI]: 80%) specificity and 100% (95% CI: 37%)/78% (95% CI: 61%) sensitivity for detection of CRC/AA. In a secondary analysis, excluding surveillance subjects, the 97-subject screening cohort yielded 91% (95% CI: 79%) specificity and CRC/AA sensitivity at 100% (95% CI: 37%)/83% (95% CI: 56%, 87% for advanced neoplasia 95% CI: 64%). Significant associations (P < .0001) were detected between FirstSight scores and adenoma size, number, and ordinally increasing pathology classification. A multimodal blood testthat included CECs and somatic mutations with adjustment for age and sex demonstrated high sensitivity for the diagnosis ofadvanced colorectal neoplasia. The resulting score captures prognostic information for CRC progression of index adenoma size and number and has the potential to enable stratification of patients for screening or postpolypectomy surveillance colonoscopy.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.