Selective destruction of cancers after exposure to heat

Abstract

Experiments in mice, dogs, and humans show that heat selectively damages tumor cells and makes them more sensitive to ionizing radiation. Observations on the effect of heat and radiation on three types of transplantable tumors in mice show that the destructive effects of heat begin at 42 deg C, at which temperature it takes several hours to damage tissues. For each degree that the temperature rises above 42 deg C, the time of exposure required to obtain the same biologic effect can be halved so that exposure of less than a minute at 49 deg is equivalent to 2 hr at 42 deg . The tumors were transplanted to the hind feet of mice and were heated in a constant-temperature bath. The tumors showed a spectrum of heat sensitivity that correlated closely with the radiosensitivity of the same kind of tumors. The effects of radiation on even the most radioresistant tumors as well as on normal tissues was greatly increased when the tissues were heated just before or just after the radiation was given. Although heat-resistant cancers that are heated to 44 deg C for 30 min. before they are irradiated can be destroyed by less than half the dosemore » of radiation that is normally required, heating induces a similar potentiation of the radiation effect on normal tissues. It is thus difficult to be sure that radiation combined with heat is any more effective than a larger dose of radiation would be if given alone. However, aome radioresistant tumors, such as the T241 sarcoma implanted on the feet of C57BL6 mice, can be controlled by heat and radiation without damage to the foot, whereas larger doses of radiation alone usually fail to cure, or in doing so damage the normal tissues. A higher proportion of mice with S9l melanoma also can be cured by combining radiation and heat than by employing either treatment alone. It was also established that there are tumors in dogs and man that can be selectively destroyed by heat without damage to the surrounding tissues, but these heat-sensitive tumors are rare, and unless they are superficially located there is as yet no safe way to apply the heat. More practicable from the clinical standpoint is the use of heat to potentiate the effects of radiation. This was employed in cutaneous recurrences of human breast cancer, and in the treatment of a malignant myoblastoma of the face, metastatic adenosarcomas in the liver, osteogenic sarcomas, and metastatic carcinomas and sarcomas in bone. Heat sensitized the superficially heated tumors to radiation, so that after immersion of the skin in a bath at 44 deg to 46 deg C for an hour, a single 600 r dose may destroy the tumor. In the conventional x-ray treatment, 1500 r or more would be required to accomplish the same result. It seems that the inflammatory reaction that follows heating rather than the heat itself selectively destroys the tumor. Of a large number of compounds tested to increase the effectiveness of heat, the only one that was consistently effective was serotonin. To a much lesser extent histamine, angiotensin, carbolines, and ethyl alcohol were effective. None of the most commonly used anticancer agents increased the effectiveness of heat. When 2.5 mg of serotonin is injected in a tumor before it is heated, the tumor can be destroyed with less than half of the exposure to heat that is normally required. Since serotonin is involved in inflammation, this also suggests that inflammation is involved in destruction of tissue after heating. (BBB)« less