Clinical results of thermoradiotherapy for various tumors at Kyoto University were reviewed with a special attention to the relationship between thermometry results and tumor response. Thermometry for superficial and subsurface tumors were satisfactory, and continuous multipoint thermometry could be performed for the tumors. Thermal parameters predicting complete tumor regression were minimum tumor temperature, minimum equivalent time at 43°C, and number of the treatment goal heat sessions. On the other hand, thermal data obtained were insufficient for deep-seated tumors, and no significant relationship could be demonstrated between tumor response and thermal parameters for deep-seated tumors. On the other hand, significant correlation between tumor degeneration and intravesical temperatures was demonstrated for bladder tumors. Until non-invasive thermometry is available clinically, temperature measurements of bladder or rectal cavity can be an alternative method of direct insertion of thermal probes into the pelvic tumors. Because a significant relationship between certain thermal parameters and tumor response was demonstrated for superficial tumors, stringent quality control of thermometry is required for the success of clinical hyperthermia of both superficial and deep-seated tumors.

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Heat shock proteins (HSPs) are like a double edged sword and can prove beneficial or detrimental. Where as HSPs protect cells against the lethal effects of heat shock and other environmental and pathophysiologic stresses, they have also been implicated in cancer drug resistance. Mammalian cells, when exposed to a non-lethal heat shock, have the ability to acquire a transient resistance to subsequent exposures at elevated temperatures. At the molecular level, heat shock activates a specific set of genes, so-called heat shock genes, and results in the preferential synthesis of HSPs. These proteins enable the cell to survive and recover from stressful conditions through mechanisms which are incompletely understood. HSPs besides their putative role in thermotolerance and in signal transduction pathways of different cell regulators, may also play a role in resistance to cytotoxic drugs. HSP expression are suppressed or activated by different chemicals and biological compounds and these effects offer a potential for therapeutic intervention.

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This paper reviews experimental research on the combined use of low dose-rate (LDR) brachytherapy and mild temperature hyperthermia (MTH). The paper also refers to our basic concept, preliminary clinical results and further research on this combination therapy. In biological research in the past two decades, there is a general agreement that MTH around 41°C can reduce the LDR sparing effect. The potential advantages of combined use of MTH and LDR brachytherapy are (A) readily applicable to concurrent exposure, (B) greater repair inhibition rather than MTH with high dose-rate (HDR) irradiation, and (C) good distribution of both the radiation dose and temperature when interstitial hyperthermia can be applied. We recommend this combined treatment for large recurrent tumors with inhomogenious dose distribution. In our clinical results, half of the large recurrent tumors were able to be controlled. Further studies, which will clarify the best treatment schedule and produce better treatment devices, are desirable to facilitate clinical use.

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The purpose of this hyperthermic study was to clarify to the possibility of dextren magnetite complex (DM) for the head and neck region. DM is a colloidal suspension of subdomain particles. It is known that DM efficiently genarates the heat under alternating current (AC) magnetic field by its physio-chemical characteristics. In our study, DM were injected into the normal tongue of golden hamsters at various iron concentrations and the tongue was heated by 500 kHz AC magnetic field. At the different iron concentrations of 112, 56, and 42 mg/ml, the tongue temperature reached to approximately 43°C at the time points of 60, 120, and 570 seconds respectively. Nevertheless, at an iron concentration of 28 mg/ml, the desireable temperrature was not obtained in spite of heating for 660 seconds. Furthermore, at the optimum iron concentration of 56mg/ml, the temperature maintenance study was performed by changing the AC magnetic field strength. The temperature of DM injected tongue could be maintained at approximately 43°C for 30 minutes. For this heating period, the contralateral tongue into which DM was not injected was slightly heated up to approximately 34.5°C and the rectal temperature had been kept at approximately 31.0°C. After the heating study, the radiographic and histological distributions of DM were examined. In radiographic image, the homogenous shadow of DM were obserbed in the half side of the tongue. HE staining demonstrated that the accumulation of DM was seen in the connective tissue between the musclar fibers. We believe that this hyperthermic system may be useful for head and neck cancer therapy.

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