title: A discrimination index for selecting markers of tumor growth dynamic across multiple cancer studies with a cure fraction.
abstract: To identify genomic markers with consistent effect on tumor dynamics across multiple cancer series, discrimination indices based on proportional hazards models can be used since they do not depend heavily on the sample size. However, the underlying assumption of proportionality of the hazards does not always hold, especially when the studied population is a mixture of cured and uncured patients, like in early-stage cancers. We propose a novel index that quantifies the capability of a genomic marker to separate uncured patients, according to their time-to-event outcomes. It allows to identify genomic markers characterizing tumor growth dynamic across multiple studies. Simulation results show that our index performs better than classical indices based on the Cox model. It is neither affected by the sample size nor the cure rate fraction. In a cross-study of early-stage breast cancers, the index allows to select genomic markers with a potential consistent effect on tumor growth dynamics.
authors.affiliation: Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore. rouamsl@gis.a-star.edu.sg
authors.forename: Sigrid
authors.initials: S
authors.lastname: Rouam
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D003198:Computer Simulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: Cancer; Clinical research; Cure model; Discrimination; Genomics; Pseudo-R(2); Survival