title: Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications.
abstract: Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.
authors.affiliation: Departamento de Matemáticas, Universidad de Castilla-La Mancha, ETSI Industriales, Avda. Camilo José Cela 3, 13071 Ciudad Real, Spain victor.perezgarcia@uclm.es.
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Pérez-García
authors.affiliation: Mathematics Department, Technical University of Lodz, Lodz, Wolczanska 214 Street, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bogdanska
authors.affiliation: Departamento de Matemáticas, Universidad de Castilla-La Mancha, ETSI Industriales, Avda. Camilo José Cela 3, 13071 Ciudad Real, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Martínez-González
authors.affiliation: Departamento de Matemáticas, Universidad de Castilla-La Mancha, ETSI Industriales, Avda. Camilo José Cela 3, 13071 Ciudad Real, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Belmonte-Beitia
authors.affiliation: Universitätsklinik für Neurochirurgie, Bern University Hospital, CH-3010 Bern, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schucht
authors.affiliation: Radiotherapy Unit, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Romasanta
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy*; D018450:Disease Progression; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008962:Models, Theoretical; D016896:Treatment Outcome
keywords: low-grade gliomas; mathematical model of tumour response; radiotherapy