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NO-54. MODELING TUMOR GROWTH KINETICS AND ITS IMPLICATIONS FOR TTFIELDS TREATMENT PLANNING [Abstracts From SNO 2010]


Posted on: 10/22/2010

NO-54. MODELING TUMOR GROWTH KINETICS AND ITS IMPLICATIONS FOR TTFIELDS TREATMENT PLANNING

Abstract

INTRODUCTION: Tumor-treating fields (TTFields) are a novel cancer treatment that has been tested extensively in vitro, in vivo, and in pilot clinical trials. However, the optimal treatment duration and minimal exposure time to TTFields needed to reverse tumor growth have not been determined. To clarify these issues, a tumor growth kinetics model based on published data and models was used to predict the optimal treatment paradigms for the new treatment. METHODS: Tumor growth kinetics were studied by means of a multicompartment model. The model reflects the balance between the changes occurring in the number of dormant and replicating cells on the one hand, and cells that die “naturally” or as a result of TTFields treatment, when applied, on the other hand. The rate constants of shift from one compartment to the other, the replication rate, and other parameters used in the numerical solution were derived from published data. Finally, the model results were validated by qualitative comparison to an animal tumor experiment and pilot clinical trials using TTFields. RESULTS: The main predictions of the model were that when exposed continuously to TTFields, tumors, such as glioblastoma, ceased to increase in size and began to shrink after about 4 weeks. This behavior was consistent with data obtained using VX-2 tumors in an animal model as well as results obtained in recurrent GBM patients and patients with breast cancer metastasis that received continuous TTFields treatment. The consequences of cessation of TTFields treatment on subsequent tumor growth were also calculated and found to be consistent with pilot clinical data. CONCLUSIONS: The model solution of glioblastoma growth kinetics and the supporting preclinical and clinical data indicate that, unlike chemotherapy, TTFields must be applied continuously for at least 4 weeks in order to achieve tumor growth stabilization and subsequent reversal.

 

 


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