RADIOTHERAPY WITH OR WITHOUT HYPERTHERMIA IN THE TREATMENT OF SUPERFICIAL LOCALIZED BREAST-CANCER - RESULTS FROM 5 RANDOMIZED CONTROLLED TRIALS

Purpose: Claims for the value of hyperthermia as an adjunct to radioth erapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, random ized Phase III trials were needed. Methods and Materials: Five randomi zed trials addressing this question were started between 1988 and 1991 . In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in p reference to surgery. In addition, heating of the lesions and treatmen t with a prescribed (re)irradiation schedule had to be feasible and in formed consent was obtained. The primary endpoint of all trials was lo cal complete response. Slow recruitment led to a decision to collabora te and combine the trial results in one analysis, and report them simu ltaneously in one publication. Interim analyses were carried out and t he trials were closed to recruitment when a previously agreed statisti cally significant difference in complete response rate was observed in the two larger trials. Results: We report on pretreatment characteris tics, the treatments received, the local response observed, duration o f response, time to local failure, distant progression and survival, a nd treatment toxicity of the 306 patients randomized. The overall CR r ate for RT alone was 41% and for the combined treatment arm was 59%, g iving, after stratification by trial, an odds ratio of 2.3. Not all tr ials demonstrated an advantage for the combined treatment, although th e 95% confidence intervals of the different trials all contain the poo led odds ratio. The greatest effect was observed in patients with recu rrent lesions in previously irradiated areas, where further irradiatio n was limited to low doses. Conclusion: The combined result of the fiv e trials has demonstrated the efficacy of hyperthermia as an adjunct t o radiotherapy for treatment of recurrent breast cancer. The implicati on of these encouraging results is that hyperthermia appears to have a n important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia ar e warranted.