The overall objective of this proposal is to deliver true simultaneous radiation and hyperthermia treatments safely and with tumor thermal doses consistent with heat induced radiosensitization. There are three major components to this project: 1) Simultaneous superficial thermoradiotherapy clinical trials that seek to optimize thermal dose delivery and determine normal tissue tolerance; 2) Hyperthermia technology R&D; and 3) In vitro cell studies to define thermal dose objectives for the clinic. This proposal is for a new clinical trial that will evaluate the long-term normal tissue effects and local control of simultaneous thermal and radiotherapy vs. radiotherapy alone in curable but high risk patients with breast carcinoma. Hypotheses are: 1) It is possible to achieve minimum tumor thermal doses (equivalent times at 41C >60 minutes) in the clinic that are compatible with heat induced radiosensitization in vitro when radiation and hyperthermia are delivered simultaneously. Moreover, the overall minimum tumor thermal dose is improved with increasing number of hyperthermia sessions. 2) The thermal enhancement of subacute and late radiation injury from these thermal doses is tolerable and its thermal dose dependence can be characterized. 3) A minimum improvement of 10 to 15 percent in local control within the heated portion of the chest wall will be detected.
Specific Aim : In a population of patients with no prior radiotherapy and minimal disease volume but high risk breast cancer, the aplicants will conduct a prospective clinical trial comparing skin and soft tissue changes between heated and non-heated portions of the chest wall (each patient is her own control) to determine the impact of superficial simultaneous hyperthermia and radiation on late radiation effects and local control. The radiotherapy will be conventionally fractionated and will include conventional boosts. The number of hyperthermia treatments will be four in the first arm of this study and will be escalated to eight in the second arm. The hyperthermia field size will be the maximum obtainable (12 cm x 12 cm) and will be directed to the medial or lateral portion of the chest wall (site selected by randomization). Skin/subcutaneous tissue changes will be graded according to the RTOG Late Effects of Normal Tissue (LENT) scale and contracture of skin will be measured by following reference tattoos in the heated and non-heated portions of the chest wall. The main potential benefit to patients is a greater likelihood of local control within the treated volume with tolerable long-term tissue effects. This benefit outweighs the potential risks from the therapy. This study may have a significant beneficial impact for patients with residual high-risk breast carcinoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA071638-05
Application #
6489249
Study Section
Radiation Study Section (RAD)
Program Officer
Stone, Helen B
Project Start
1996-09-01
Project End
2005-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
5
Fiscal Year
2002
Total Cost
$207,900
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Varma, Sumeeta; Myerson, Robert; Moros, Eduardo et al. (2012) Simultaneous radiotherapy and superficial hyperthermia for high-risk breast carcinoma: a randomised comparison of treatment sequelae in heated versus non-heated sectors of the chest wall hyperthermia. Int J Hyperthermia 28:583-90
Moros, Eduardo G; Peñagaricano, Jose; Novàk, Petr et al. (2010) Present and future technology for simultaneous superficial thermoradiotherapy of breast cancer. Int J Hyperthermia 26:699-709
Myerson, Robert J; Singh, Anurag K; Bigott, Heather M et al. (2006) Monitoring the effect of mild hyperthermia on tumour hypoxia by Cu-ATSM PET scanning. Int J Hyperthermia 22:93-115
Novak, P; Moros, E G; Parry, J J et al. (2005) Experience with a small animal hyperthermia ultrasound system (SAHUS): report on 83 tumours. Phys Med Biol 50:5127-39
Myerson, R J; Roti Roti, J L; Moros, E G et al. (2004) Modelling heat-induced radiosensitization: clinical implications. Int J Hyperthermia 20:201-12
Singh, A K; Moros, E G; Novak, P et al. (2004) MicroPET-compatible, small animal hyperthermia ultrasound system (SAHUS) for sustainable, collimated and controlled hyperthermia of subcutaneously implanted tumours. Int J Hyperthermia 20:32-44
Moros, Eduardo G; Novak, Petr; Straube, William L et al. (2004) Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound. Phys Med Biol 49:869-86
Arthur, R Martin; Straube, William L; Starman, Jared D et al. (2003) Noninvasive temperature estimation based on the energy of backscattered ultrasound. Med Phys 30:1021-9
Xu, M; Myerson, R J; Straube, W L et al. (2002) Radiosensitization of heat resistant human tumour cells by 1 hour at 41.1 degrees C and its effect on DNA repair. Int J Hyperthermia 18:385-403
Straube, W L; Klein, E E; Moros, E G et al. (2001) Dosimetry and techniques for simultaneous hyperthermia and external beam radiation therapy. Int J Hyperthermia 17:48-62

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