The effects of hyperthermia on pH, local blood flow (LBF) and tissue oxygen tension (TpO2) in several normal and tumor tissues were studied. It was found that TpO2, local blood flow and pH are inhomogeneous in tumor tissue. TpO2 is very low in certain areas which also seem deprived of blood flow and are at very low pH. Hyperthermia has a dual effect: at temperatures below 41 degrees C, it increases blood flow and TpO2 while above 41 degrees C, it causes a collapse in blood flow, lower TpO2 and a shift of the tissue pH towards acidosis from the already low pH values found in tumors.

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From September 1984 through March 1987, 30 patients with locally recurrent breast carcinoma who had been heavily pretreated with conventional modes of therapy (radiation, chemotherapy, and hormonal therapy) were entered into a phase II study of hyperthermia and low-dose irradiation. The purpose of the study was to determine the feasibility, effectiveness, and morbidity of this treatment combination. Radiation therapy was administered twice weekly, 4 Gy per fraction, to a total dose of 32 Gy, with 6 or 9 MeV electrons depending on the thickness of the lesions. Hyperthermia generated by microwave frequencies of 200 to 700 MHz was administered immediately after radiation therapy, with a time and temperature aim of 60 minutes at 43 degrees C. Complete response (CR) was achieved in 17 patients (57%), and partial response (PR) in 11 patients (36%). Response was positively correlated with tumor size; lesions less than 5 cm in diameter achieved CR significantly more frequently than lesions greater than or equal to 5 cm (P less than .001). Eighty percent of the complete responders continued to experience sustained control of the treated site from 6 to 32 months but showed evidence of progressive systemic disease or locoregional progression to the adjacent untreated sites, reflecting the natural history of this disease and extensive dermal lymphatic permeation. True recurrence within the treated volume occurred in three patients. Nonhealing ulceration developed in nine patients and seven of those were associated with persistent tumor. This study confirms the palliative value of hyperthermia in combination with radiotherapy for previously irradiated recurrent chest wall tumors and sets the scene for its comparative clinical evaluation against radiation therapy alone as first line therapy for locally recurrent breast carcinoma.