Hyperthermia: Rational and clinical applications

Over the past 20 years, research in the application of hyperthermia (HT), primarily as an adjuvant to radiation therapy (XRT), for the management of locally-advanced or recurrent malignancies, has waxed and waned in interest in the United States. Initial enthusiasm based on in vitro and murine tumor studies, was severely dampened by the results of early clinical trails. One initial clinical Phase III trial, however, employed applicators which were frequently unable to obtain adequate tumor heating, failed to sufficiently monitor tumor and normal tissue temperatures, and selected inappropriate tumors (based on size and depth) for therapy. Fortunately, subsequent clinical trials have benefited from the lessons learned in earlier attempts. Recently, three European-based, Phase III randomized trials enrolling large numbers of patients have demonstrated significantly improved local control rates for superficially-located metastatic melanomas, chest wall recurrences from breast cancer, and deep-seated locally-advanced tumors of the uterine cervix and urinary bladder. In addition, continued improvements in HT applicators and a better understanding of thermal dosimetry should permit further advances in trial design for the clinical use of HT as an adjuvant to XRT. This refresher course will focus on four areas: (1) a review of progress made in thermal dose descriptors with emphasis on their use in prescribing HT treatments and on the correlation of thermal and thermal dose parameters with clinical outcome, (2) tumor site-specific selection for HT studies based on sites that can be heated with currently available equipment, and tumors where improved local control will result in increased chance of patient cure or significant palliation, (3) site-specific results and examples of responses to XRT-HT, and (4) an overview of the results of eleven randomized Phase III clinical studies comparing XRT alone to XRT plus HT. It is hoped that those attending the refresher course will obtain a better understanding of the potential value of HT and its future promise in the treatment of selective locally-advanced or recurrent cancers