Glioblastomas are the most common form of brain tumors, but despite aggressive treatment protocols involving surgery, radiation therapy, and chemotherapy, the mean life time of these patients after diagnosis is 10 months. The long term objective is to investigate the efficacy of interstitial hyperthermia and radiation therapy as a treatment for this type of tumor. Interstitial hyperthermia involves implanting a set of 2 mm catheters in the tumor and then inserting a set of 1 mm microwave antennas into each catheter, along with a thermometry probe. The electromagnetic energy radiated from these antennas heats the tumor volume to the temperature range of 43-50 degrees C. The specific objectives of this research are to 1) continue a phase I clinical trial for the treatment of glioblastoma multiforme (Grade III and IV) in humans, 2) develop 3-dimensional computer-based thermal and radiation treatment planning models, 3) investigate the phenomenon of thermotolerance in normal and tumor tissue, 4) assess long term toxicity of combined heat and radiation in normal brain, 5) study time/temperature dose escalation effects in normal brain, 6) develop a new 2450 MHz interstitial microwave system for clinical and animal studies, and 7) measure the power deposition and thermal dosmetry for new antenna designs. The phase I clinical trial will study the efficacy of treatment of brain tumors using an interstitial microwave antenna array hyperthermia system and brachytherapy. The ability of this system to effectively heat brain tumors will be evaluated as well as the effects of increasing the heated region around the CT defined tumor margin. Fundamental studies will be conducted on questions of thermotolerance, both in normal dog brain and in an avian sarcoma virally induced tumor model. This information could lead to a better treatment protocol for the clinical trials. Thermotolerance will be assessed by neurohistological and heat shock protein analysis. The long term toxicity of combined heat and radiation will be studied for hyperthermia applied with the interstitial system and with low dose irradiation using iridium-192 seeds, again using a dog model. Various heat/radiation combinations will be assessed, i.e. heat-radiation-heat, heat-radiation, radiation-heat, and heat-radiation-heat-radiation. The time/temperature escalation study will be performed using a 915 MHz spiral surface applicator in normal dog brain and the analysis will be based on histological and neuroradiological evaluation 7 days after treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA042604-01S1
Application #
3184101
Study Section
Radiation Study Section (RAD)
Project Start
1986-08-01
Project End
1991-01-31
Budget Start
1987-08-01
Budget End
1988-01-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
Overall Medical
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Ryan, T P; Trembly, B S; Roberts, D W et al. (1994) Brain hyperthermia: I. Interstitial microwave antenna array techniques--the Dartmouth experience. Int J Radiat Oncol Biol Phys 29:1065-78
Trembly, B S; Douple, E B; Ryan, T P et al. (1994) Effect of phase modulation on the temperature distribution of a microwave hyperthermia antenna array in vivo. Int J Hyperthermia 10:691-705
Mechling, J A; Strohbehn, J W; Ryan, T P (1992) Three-dimensional theoretical temperature distributions produced by 915 MHz dipole antenna arrays with varying insertion depths in muscle tissue. Int J Radiat Oncol Biol Phys 22:131-8
Mechling, J A; Strohbehn, J W (1992) Three-dimensional theoretical SAR and temperature distributions created in brain tissue by 915 and 2450 MHz dipole antenna arrays with varying insertion depths. Int J Hyperthermia 8:529-42
Ryan, T P; Hoopes, P J; Taylor, J H et al. (1991) Experimental brain hyperthermia: techniques for heat delivery and thermometry. Int J Radiat Oncol Biol Phys 20:739-50
Ryan, T P (1991) Comparison of six microwave antennas for hyperthermia treatment of cancer: sar results for single antennas and arrays. Int J Radiat Oncol Biol Phys 21:403-13
Ryan, T P; Wikoff, R P; Hoopes, P J (1991) Design of an automated temperature mapping system for ultrasound or microwave hyperthermia. J Biomed Eng 13:348-54
Mechling, J A; Strohbehn, J W; France, L J (1991) A theoretical evaluation of the performance of the Dartmouth IMAAH system to heat cylindrical and ellipsoidal tumour models. Int J Hyperthermia 7:465-83
Trembly, B S; Douple, E B; Hoopes, P J (1991) The effect of air cooling on the radial temperature distribution of a single microwave hyperthermia antenna in vivo. Int J Hyperthermia 7:343-54
Ryan, T P; Mechling, J A; Strohbehn, J W (1990) Absorbed power deposition for various insertion depths for 915 MHz interstitial dipole antenna arrays: experiment versus theory. Int J Radiat Oncol Biol Phys 19:377-87

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