Clinical and preclinical evidence for the efficacy of concurrent hyperthermia and radiotherapy

Hyperthermia, raising the tumour temperature to 40-43°C, is a potent radiosensitiser and clinically applied in combination with Radiotherapy for various tumour sites. This presentation will review its effects and the present evidence for clinical efficacy of Thermoradiation. Multiple pleiotropic synergistic effects have been identified including direct cell kill of chronically hypoxic tumour cells, temporary blockage of multiple DNA damage repair pathways, temporary enhanced perfusion resulting in re-oxygenation of tumour cells, expression of Heat Shock Proteins (HSPs) and immunogenic effects. All of these effects display a dose-effect relationship and most are more effective for shorter time intervals between radiotherapy and hyperthermia. A good understanding of the contribution of the different effects to the effectiveness during clinical application of Hyperthermia is important. Clinical evidence confirmed the efficacy of Thermoradiation in randomized trials for many tumour sites including breast, bladder, cervix, rectum, head & neck and other cancers. The clinical data also confirm that hyperthermic radiosensitisation increases for higher temperatures and for shorter time intervals between Radiotherapy and Hyperthermia. Dose-effect relationships have been demonstrated for various tumour sites, including breast, rectum, cervix, and the importance of short time intervals was confirmed for Thermoradiation treatment of breast and cervical cancer. Thermoradiotherapy is thus a powerful, clinically proven cancer treatment, warranting further research and wider clinical application. Further studies can assess which time intervals achieve optimal balance between maximizing cytotoxic tumour effects while avoiding inducing additional normal tissue toxicity. (author)