title: A filter-flow perspective of haematogenous metastasis offers a non-genetic paradigm for personalised cancer therapy.
abstract: Research into mechanisms of haematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of 'seed-soil' relationships. Preceding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulation. Patterns of metastatic spread have been previously quantified using the metastatic efficiency index, a measure quantifying metastatic incidence for a given primary-target organ pair and the relative blood flow between them. We extend this concept to take into account the reduction in CTCs which occurs in organ capillary beds connected by a realistic vascular network topology. Application to a dataset of metastatic incidence reveals that metastatic patterns depend strongly on assumptions about the existence and location of micrometastatic disease which governs CTC dynamics on the network, something which has heretofore not been considered - an oversight which precludes our ability to predict metastatic patterns in individual patients.
authors.affiliation: Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Wolfson Centre for Mathematical Biology, Mathematical Institute, Radcliffe Observatory Quarter, University of Oxford, Woodstock Road, Oxford OX2 6GG, UK.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Scott
authors.affiliation: Wolfson Centre for Mathematical Biology, Mathematical Institute, Radcliffe Observatory Quarter, University of Oxford, Woodstock Road, Oxford OX2 6GG, UK.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Fletcher
authors.affiliation: Wolfson Centre for Mathematical Biology, Mathematical Institute, Radcliffe Observatory Quarter, University of Oxford, Woodstock Road, Oxford OX2 6GG, UK.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Maini
authors.affiliation: Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Alexander R A
authors.initials: AR
authors.lastname: Anderson
authors.affiliation: Mathematical Sciences, University of Gothenburg and Chalmers University of Technology, 412 96 Gothenburg, Sweden.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerlee
mesh_terms: D001775:Blood Circulation / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis; D009366:Neoplasm Seeding; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D057285:Precision Medicine
keywords: Circulating tumour cells; Mathematical model; Metastasis; Oligometastasis