Hyperthermia in cancer treatment: current and future prospects.

The renewed interest in the possible use of localized hyperthermia in cancer therapy is prompted by two major realizations. The first is the radiobiological evidence indicating that there may be a significant advantage in the use of heat alone or combined with radiation therapy or chemotherapy to enhance the inactivation of tumor cells The second is that early clinical investigation with refractory malignant tumors at temperatures between 41 degrees C and 45 degrees C have shown tumor regression response rate over 70% without increasing normal tissue complication. A phase I/II study using electromagnetic hyperthermia immediately following administration of ionizing radiation was begun at Duke in the fall of 1976 to evaluate the response of normal tissues, the regression of cutaneous and subcutaneous tumors, and the feasibility of such combined modalities in therapeutic radiology. Each hyperthermia session consisted of 45 minutes at 42-43.5 degrees C 2-3 times per week immediately following radiotherapy. The radiation therapy fraction size was usually 2-3 Gy 3-5 times per week with a maximum total of 48 Gy. The 60+ patients treated to date have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, liposarcoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 600 hyperthermia sessions, we have found: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a significantly higher level of preferential heat induction into tumor tissue is possible as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 degrees C for 45 minutes per session immediately following radiation therapy yields favorable therapeutic results. Tumor regression response rate of over 70% was achieved without concomitant increase of normal tissue complication. Therefore, the potentially significant impact on clinical cancer therapy, whether of curative or palliative intent, by moderate thermotherapy is evident. Technical advances to optimize such treatment methods including R & D for delivering a known localized quantity of heat to tumors in any location in the body are expected to progress rapidly. The methods with most promising potential for inducing local thermotherapy are those involving the use of electromagnetic waves, e.g., radiofrequency energy, microwave energy, and ultrasound energy.

The effect of age on the long-term response of bone marrow to local fractionated irradiation.

The in-field long-term progressive response of bone marrow to localized fractionatedradiation to the thoracic spine was observed in weanling and adult rats. Total dose levels were 1800,3600 and 5400 rads given in daily fractions of 180 rads for 900 rads perweek, to simulate the clinical setting. Animals were sacrificed at 4 1/2, 6, 8, and 10months after irradiation, and bone marrow from within the treated area was ezamined. The juvenile marrow repopulated to higher levels of cellularity and after higher doses of radiation than the adult. The degree of marrow depletion, time of repopulation, and ultimate level of repopulation after cessation of irradiation were all dependent on the total dose. Some of the suggested clinical implications include re-evaluation of the lower doses given to children.

Microwave-induced local hyperthermia in combination with radiotherapy of human malignant tumors.

Since 1976, two groups of patients have been treated with local microwave hyperthermia immediately following ionizing radiation. Group A patients had measurable multiple lesions assigned radiotherapy only, microwave hyperthermia only, or combined treatment. Ionizing radiation in 200-600 rad fractions was used 2-5 times per week to a total of 1800-4200 rad in 5-14 fractions. Group B patients had combination treatment only, with radiation fractions of 200-600 rad 2-5 times per week to a total of 2000-4800 rad total in 6-20 fractions. Both groups received hyperthermia (42-44 C) 2-3 times per week, maximum ten sessions in four weeks. The 19 patients treated have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 150 hyperthermia sessions, we find: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a higher level of heat induction in tumor tissue as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 C for 45 minutes per session immediately following photon irradiation yields a favorable therapeutic result, occasionally dramatic. Local microwave hyperthermia in combination with radiotherapy offers the possibility of substantial impact on clinical cancer therapy, whether of curative or palliative intent.