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Centre for Mathematical Medicine Seminar Series 2004-2005


May 27, 2005 -- 4:30 p.m.
talk to be held at Bahen Centre

J. Carl Panetta, Department of Pharmaceutical Sciences,
St. Jude Children's Research Hospital and University of Tennessee,

Modeling Chemotherapy Induced Myelosuppression

Temozolomide (TMZ) and Topotecan (TPT) are currently being evaluated for the treatment of several pediatric cancers including high-grade gliomas, neuroblastoma, medulloblastoma, rhabdomyosarcoma, and acute leukemias. Myelosuppression is the dose-limiting toxicity for both TMZ and TPT. Empirical methods (i.e. relations between the percent change in absolute neutrophil count (ANC) and the area under the plasma concentration curve (AUC)) show poor results when attempting to describe myelosuppression from serial data. Therefore, to improve our understanding of the myelosuppressive effects of TMZ and TPT in children we developed a mechanistic mathematical model. The model describes the progression of neutrophils from their production in the bone marrow to their release in the plasma. Included in the model are the feedback effects of granulocyte colony stimulating factor (G-CSF), which stimulates neutrophil production when there is a decrease in circulating neutrophils. Post TMZ or TPT dose serial ANC measurements are fit to the model. The model is able to explain, among other things, the lag in ANC reduction following a dose and a "rebound effect" observed where the ANC recovers to levels greater than pre-dose. The mathematical model is then used to predict the extent of myelosuppression given various TMZ/TPT/G-CSF dosing schedules. This model will be useful for the prospective design of clinical trials of TMZ and TPT in children with brain tumors.
Short Bio:
Dr. J.C. Panetta completed his PhD in 1995 at Old Dominion University and was subsequently Professor of Mathematics at Penn State Erie, The Behrend College, Erie PA. He is currently a Biomedical Modeller at St. Jude Children's Research Hospital in Memphis, Tennessee and Adjunct Professor in the Department of Pharmaceutical Sciences at the University of Tennessee. Dr. Panetta is also on the Board of Directors of the Society for Mathematical Biology.


March 2, 2005 - 4:00 p.m.
Kristin R. Swanson, PhD, Shaw Research Assistant Professor, Pathology, University of Washington

Clinical applications of quantitative modeling for invasive brain tumors (gliomas)
Gliomas account for over half of all primary brain tumors and have been studied extensively for decades. Even with increasingly sophisticated medical imaging technologies, gliomas remain uniformly fatal lesions. A significant gap remains between the goal of designing effective therapy and the present understanding of the dynamics of glioma progression. It has become increasingly clear that, along with the proliferative potential of these neoplasms, it is the subclinically diffuse invasion of gliomas that most contributes to their resistance to treatment. That is, the inevitable recurrence of these tumors is the result of diffusely invaded but practically invisible tumor cells peripheral to the abnormal signal on medical imaging and to the limits of surgical, radiological and chemical treatments.

In this presentation, I will demonstrate how quantitative modeling can not only shed light on the spatio-temporal growth of gliomas but also can have specific clinical application in real patients. Integration of our quantitative model with the T1-weighted and T2-weighted MR imaging characteristics of gliomas can provide estimates of the extent of invasion of glioma cells peripheral to the imaging abnormality. Further model analysis reveals remarkable concordance with patient survival rates. In summary, although current imaging techniques remain woefully inadequate in accurately resolving the true extent of gliomas, quantitative modeling provides a new approach for the dynamic assessment of real patients and helps direct the way to novel therapeutic approaches.

Dr. Kristin R. Swanson received her B. S. for Tulane University in 1996 followed by her Ph.D. from the University of Washington in 1999 under the direction of Professor J.D. Murray, FRS. She is currently the Shaw Research Assistant Professor of Neuropathology in the University of Washington School of Medicine as well as an adjunct research assistant professor of Applied Mathematics. Her research focuses on the application of quantitative modeling techniques to biomedical problems including brain tumor invasion, dynamics of serum markers for prostatic tumor growth, wallerian degeneration in stroke victims, PET tracer kinetics and thymic function following immunosuppression.

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