RESUMEN
We optimize radiotherapy (RT) administration strategies for treating low-grade gliomas. Specifically, we consider different tumour growth laws, both with and without spatial effects. In each scenario, we find the optimal treatment in the sense of maximizing the overall survival time of a virtual low-grade glioma patient, whose tumour progresses according to the examined growth laws. We discover that an extreme protraction therapeutic strategy, which amounts to substantially extending the time interval between RT sessions, may lead to better tumour control. The clinical implications of our results are also presented.
Asunto(s)
Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Glioma/patología , Glioma/radioterapia , Modelos Biológicos , HumanosRESUMEN
Diabetes mellitus constitutes a major health problem and its clinical presentation and progression may vary considerably. A number of standardized diagnostic and monitoring tests are currently used for diabetes. They are based on measuring either plasma glucose, glycated haemoglobin or both. Their main goal is to assess the average blood glucose concentration. There are several sources of interference that can lead to discordances between measured plasma glucose and glycated haemoglobin levels. These include haemoglobinopathies, conditions associated with increased red blood cell turnover or the administration of some therapies, to name a few. Therefore, there is a need to provide new diagnostic tools for diabetes that employ clinically accessible biomarkers which, at the same time, can offer additional information allowing us to detect possible conflicting cases and to yield more reliable evaluations of the average blood glucose level concentration. We put forward a biomathematical model to describe the kinetics of two patient-specific glycaemic biomarkers to track the emergence and evolution of diabetes: glycated haemoglobin and its labile fraction. Our method incorporates erythrocyte age distribution and utilizes a large cohort of clinical data from blood tests to support its usefulness for diabetes monitoring.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Eritrocitos/metabolismo , Hemoglobina Glucada/metabolismo , Modelos Biológicos , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/patología , Eritrocitos/patología , Humanos , Cinética , Monitoreo FisiológicoRESUMEN
Low grade gliomas (LGGs) are infiltrative and incurable primary brain tumours with typically slow evolution. These tumours usually occur in young and otherwise healthy patients, bringing controversies in treatment planning since aggressive treatment may lead to undesirable side effects. Thus, for management decisions it would be valuable to obtain early estimates of LGG growth potential. Here we propose a simple mathematical model of LGG growth and its response to chemotherapy which allows the growth of LGGs to be described in real patients. The model predicts, and our clinical data confirms, that the speed of response to chemotherapy is related to tumour aggressiveness. Moreover, we provide a formula for the time to radiological progression, which can be possibly used as a measure of tumour aggressiveness. Finally, we suggest that the response to a few chemotherapy cycles upon diagnosis might be used to predict tumour growth and to guide therapeutical actions on the basis of the findings.
Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Dacarbazina/análogos & derivados , Glioma/tratamiento farmacológico , Glioma/patología , Modelos Biológicos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Proliferación Celular/efectos de los fármacos , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Progresión de la Enfermedad , Femenino , Glioma/diagnóstico , Glioma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , TemozolomidaRESUMEN
Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility.