Abstract
Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient's disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [18F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning.
Highlights
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumour and accounts for the majority of primary brain tumours [1]
In order to investigate the role of hypoxia in mediating response to radiation therapy (RT), we studied an magnetic resonance imaging (MRI)-based patient-specific computational model of tumour growth and response to RT and combined it with hypoxia determined with [18F]-fluoromisonidazole (FMISO) positron emission tomography (PET) [13,14]
Using our patient-specific model for glioma growth and response to RT, we find the incorporation of hypoxia-mediated radiation resistance defined with FMISO-PET leads to an order of magnitude decrease in relative volumetric error, from 14.6% to 1.1%
Summary
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumour and accounts for the majority of primary brain tumours [1]. GBM is often treated with surgical intervention followed by concurrent radiation and chemotherapy [2]. GBM is characterized by invasive tumour cells that can be found as far away as 4 cm from the tumour mass [3]. This tumour cell invasion is not revealed by magnetic resonance imaging (MRI), the principal means of monitoring GBM progression and response to therapy [4]. License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
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