Results of Randomized Studies on Hyperthermia in Oncology

Abstract

The review presents statistics of published randomized phase III trials on the addition of hyperthermia (HT) to other cancer therapies, and analyzes the results of these trials. In total, 47 comparisons could be made for treatments with or without HT. These trials were done in a large variety of solid tumors, and in centers in Asia, Europe, North America and Australia. In general, these studies were relatively small – 17 studies included more than 100 patients. The total number of patients was 5099. In the majority of the studies, HT was applied with electromagnetic radiation. Most studies (74 %) have shown that additional HT significantly improves the results of radiation, chemo- and chemoradiotherapy in patients with, in general, locally advanced relapsed and metastatic forms of malignant tumors. Improved results were reported for complete and overall response, loco-regional tumor control, disease free and overall survival, and, in one study, for palliative effects. In these randomized trials also acute and/or late toxicity has been investigated. In the majority of the trials, addition of HT did not result in significant increases of toxic effects. The economic consequences of HT as part of cancer treatment are discussed. Twenty-six percent of the studies failed to show a significant beneficial effect of HT which are discussed in more detail. In 4 studies with a trend of a better outcome in the plus HT treatment arm, with an absolute difference of 10 % or more, the lack of significance is probably due to a low number of patients included. In other studies, there was an unbalanced distribution of tumor characteristics over the two study arms, with worse prognostic factors in the plus HT arm, inadequate techniques, using too high frequency of electromagnetic radiation, and/or a small applicator, and/or a short heating time, so that a sufficient energy deposition in the tumor volume could not be achieved. These results make clear that it is important to develop guidelines for the application of HT, in addition to the existing ones. In view of the different principles of operation of HT applicators, it is important that such guidelines will become available for each individual device. Further, it is important to conduct larger randomized trials. Larger studies would probably increase the number of significant and also more relevant outcomes, and promote a wider acceptance of HT as part of cancer treatment.