Hyperthermia is a modality that appears to be very promising as an adjuvant to radiation therapy in the treatment of cancer. The basis for the effectiveness of hyperthermia in tumor therapy may be the decreased extracellular pH in solid tumors and differences between neuromuscular elements of tumors versus normal tissue vasculature. This project proposes: 1) to evaluate the extracellular pH in human tumors for the purpose of predicting therapeutic outcome based on Ph measurements; 2) to evaluate tumor pH changes as a function of time after hyperthermia; and 3) to manipulate the pH distributions in human tumors by glucose administration. Glucose concentration and route of administration (oral, i.v., bolus, i.v. infusion) will be varied to determine the most effective technique for lowering tumor pH. In addition, human tumor pH will be correlated with other physiologic parameters such as tumor blood flow. Measurement of blood flow will be accomplished by a laser doppler probe, by a thermal dilution probe or by thermal washout techniques currently utilized during hyperthermia treatment sessions in conjunction with a separately NIH funded study. All tumor bearing patients given glucose will have relative blood flow determinations by the laser doppler probe at every point where pH is measured. Jefferson's Department of Radiation Therapy has a large patient base that will be utilized for this study. Tumor response rates in patients with tumors refractory to surgery, radiation therapy, and/or chemotherapy have been on the order of 40% complete response and an overall 80% combined partial and complete response. Preliminary results have shown in 5 of 9 patient tumors that 100 gm of oral glucose will decrease tumor pH by up to 0.4 pH units. Three of the four patients who did not show a reduction in tumor pH were found to be subclinical diabetics, and their tumor pH actually rose 0.3-0.5 pH units with increased blood glucose concentration rather than declined. Our hypothesis is that tumor pH can predict tumor response to hyperthermia and that the local control rate of human tumors after hyperthermia and radiation can be improved by manipulation of pH and blood flow.
| Leeper, D B; Engin, K; Wang, J H et al. (1998) Effect of i.v. glucose versus combined i.v. plus oral glucose on human tumour extracellular pH for potential sensitization to thermoradiotherapy. Int J Hyperthermia 14:257-69 |
| Engin, K; Leeper, D B; Cater, J R et al. (1995) Extracellular pH distribution in human tumours. Int J Hyperthermia 11:211-6 |
| Leeper, D B; Engin, K; Thistlethwaite, A J et al. (1994) Human tumor extracellular pH as a function of blood glucose concentration. Int J Radiat Oncol Biol Phys 28:935-43 |
