The objective of this project is to integrate quantitative thermal modeling tools into clinical hyperthermia to improve treatment planning, delivery, and evaluation. We focus particularly on the application and validation of these models, in combination with extensive thermometry and perfusion measurements, to prostate disease. This allows us to validate thermal models ina a consistent, reproducible, and relatively accessible anatomic site that can be well instrumented for temperature, perfusion and SAR. In the current grant period, efforts have been strongly technology oriented; the development and evaluation of thermal models and algorithms for predictive and reconstructive temperature field calculations. We developed the Basis Element Method (BEM), a rapid, tunable technique for temperature field calculations in the clinical setting. Initial experimental validation of the BEM thermal model in animal (pig) experiments and selected patient treatment sessions show that the BEM, with sparsely measured SAR and perfusion, is able to predict temperatures with RMS differences of 0.9 degree C. The renewal is clinically oriented; to transfer to the clinic and integrate into the patient treatment system these quantitative thermal modeling techniques. The BEM and associated reconstruction and visualization modules will be transferred to the DFCI, along with clinical refinements that include optimization for clinical use and customization for the specific anatomic sites of interest in the Program Project. Additional clinically driven refinements to the BEM include the real-time application of the thermal reconstruction algorithm for use in the control of treatment delivery. To support and enhance these models, we also provide the hyperthermia clinic with the necessary dense temperature and perfusion measurement capability. These modeling and analysis capabilities will be used to establish a rational basis for therapy planning and optimization based on individual patient geometric and anatomic data. Equally important, this will allow the evaluation of treatment efficacy by reconstruction of the treatment temperature field from data gathered at discrete measurement sites, calculation of volumetric thermal dose distributions over the entire tumor volume, and correlation with outcome. This will enable more effective and quantitative assessment of the therapeutic value of hyperthermia.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA031303-10A1
Application #
5207144
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1996
Total Cost
Indirect Cost
Hurwitz, Mark D; Hansen, Jorgen L; Prokopios-Davos, Savina et al. (2011) Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer: long-term results from Dana-Farber Cancer Institute study 94-153. Cancer 117:510-6
Wang, XiaoZhe; Khaleque, Md Abdul; Zhao, Mei Juan et al. (2006) Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding. J Biol Chem 281:782-91
Hurwitz, Mark D; Kaplan, Irving D; Hansen, Jorgen L et al. (2005) Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile. Int J Hyperthermia 21:649-56
Calderwood, Stuart K (2005) Regulatory interfaces between the stress protein response and other gene expression programs in the cell. Methods 35:139-48
Calderwood, Stuart K; Theriault, Jimmy R; Gong, Jianlin (2005) How is the immune response affected by hyperthermia and heat shock proteins? Int J Hyperthermia 21:713-6
Calderwood, S K (2005) Evolving connections between molecular chaperones and neuronal function. Int J Hyperthermia 21:375-8
Tang, Dan; Khaleque, Md Abdul; Jones, Ellen L et al. (2005) Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones 10:46-58
Calderwood, Stuart K; Theriault, Jimmy R; Gong, Jianlin (2005) Message in a bottle: role of the 70-kDa heat shock protein family in anti-tumor immunity. Eur J Immunol 35:2518-27
Ciocca, Daniel R; Calderwood, Stuart K (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86-103
Tonkiss, J; Calderwood, S K (2005) Regulation of heat shock gene transcription in neuronal cells. Int J Hyperthermia 21:433-44

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