Quantifying efficacy of chemotherapy of brain tumors with homogeneous and heterogeneous drug delivery.
Gliomas are diffuse and invasive brain tumors with the nefarious ability to evade even seemingly draconian treatment measures. Here we introduce a simple mathematical model for drug delivery of chemotherapeutic agents to treat such a tumor. The model predicts that heterogeneity in drug delivery related to variability in vascular density throughout the brain results in an apparent tumor reduction based on imaging studies despite continual spread beyond the resolution of the imaging modality. We discuss a clinical example for which the model-predicted scenario is relevant. The analysis and results suggest an explanation for the clinical problem of the long-standing confounding observation of shrinkage of the lesion in certain areas of the brain with continued growth in other areas.
Swanson
Kristin R
KR
Department of Pathology, Laboratory of Neuropathology, 325 - 9th Avenue, Box 359791, Harborview Medical Center, Seattle, Washington 98104-2499, USA.
Alvord
Ellsworth C
EC
Murray
J D
JD
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004058:Diffusion; D016503:Drug Delivery Systems; D005544:Forecasting; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008954:Models, Biological; D016896:Treatment Outcome
D000970:Antineoplastic Agents