title: A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.
abstract: Barrett's esophagus (BE) patients are routinely screened for high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC) screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC) in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1) the probability that small cancers are missed during biopsy-based screening, (2) the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3) the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence.
authors.affiliation: Department of Applied Mathematics, University of Washington, Seattle, Washington, United States of America.
authors.forename: Kit
authors.initials: K
authors.lastname: Curtius
authors.affiliation: Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: William D
authors.initials: WD
authors.lastname: Hazelton
authors.affiliation: Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jihyoun
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: E Georg
authors.initials: EG
authors.lastname: Luebeck
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000503:physiopathology; D000465:Algorithms; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000503:physiopathology; D001706:Biopsy; D002138:Calibration; D003198:Computer Simulation; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000503:physiopathology; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008403:Mass Screening; D008962:Models, Theoretical; D015995:Prevalence; D011336:Probability; D015203:Reproducibility of Results; D013269:Stochastic Processes