Combined interstitial irradiation and localized current field hyperthermia: results and conclusions from clinical studies.

Low-dose-rate continuous irradiation in conjunction with localized current fields has been investigated in Phase I human trials at several institutions since 1977. To date, nearly 100 patients with a variety of malignant lesions (carcinomas, melanomas, sarcomas, lymphomas) in different anatomical locations (skin, head and neck, breast, pelvis, extremities) have been entered into experimental protocols. Different radiation and thermal dose levels have been evaluated. Significant progress in equipment and techniques has been accomplished. A wide range of complete response rates (38 to 83%) and complication rates (7 to 25%) has been reported. Analysis of results showed a good correlation of complete response rates with the radiation dose level and minimum temperature. The most successful regimens included either an "optimal radiation dose" (greater than 6000 rads) or an "effective time-averaged minimum temperature" (44 degrees). Important considerations in the design of clinical trials for Phases II and III are: (a) in regimens with curative aim, a hyperthermic effect may not be achieved in all regional sites of disease, especially in those areas harboring subclinical disease. Radiation dose-fractionation schedules of proven adjuvant efficacy thus must be used; (b) whether the total radiation dose to the site of bulky disease when combined with hyperthermia can be reduced without loss of therapeutic efficacy relative to conventional radiation doses is critically dependent upon minimum temperatures and uniformity of temperature within the tumor; (c) optimized combined therapy is likely to reflect a high level of quality assurance in administering both the interstitial irradiation and the interstitial hyperthermia; (d) the present criteria for evaluation of tumor response (no response, partial response, and complete response) are clinically meaningless. The criterion, "local control" or "failure," should be adopted in future trials in Phases II and III with the curative aim to allow comparison of results with historical or concurrent controls treated with radiation alone.