title: Modeling minimal residual disease (MRD)-testing.
abstract: There is considerable effort to develop more sensitive methods to detect minimal residual disease (MRD) in bone marrow and blood samples of persons with cancer. Results of MRD-testing are used to predict clinical outcome and determine if more anti-cancer therapy is needed. Mathematical models were developed to assess factors affecting sensitivity and specificity of MRD-testing at diverse cancer cell prevalences. Modeling results and predictions were compared to results of large published studies.Accuracy of MRD-testing depends on cancer cell prevalence and distribution in the blood or bone marrow of the subject, sensitivity and specificity of the MRD-test and sample size. In subjects with low cancer cell prevalences (< or = 10(-4)) results of MRD testing are likely inaccurate. Increasingly sensitive MRD-tests are only marginally useful; the major obstacle to accuracy is inadequate sampling. Increasing sensitivity of methods to detect MRD is unlikely sufficient to increase accuracy of MRD-testing. In contrast, increased sampling (size and frequency) and assigning a high cut-off value (for example, > or = 10(-3)) to declare a MRD-test positive will increase sensitivity and specificity, respectively.
authors.affiliation: Department of Pediatrics, Division of Hematology Oncology, Childrens' Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027-6016, USA. abutturini@chla.usc.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Butturini
authors.forename: John
authors.initials: J
authors.lastname: Klein
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
mesh_terms: D015415:Biomarkers; D003951:Diagnostic Errors; D005188:False Negative Reactions; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D011237:Predictive Value of Tests; D012008:Recurrence; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers