Site and disease selection for hyperthermia clinical trials

Abstract

Significant progress has been made in the past 20 years in understanding the biological basis of hyperthermia-induced cytotoxicity, thermoenhancement of radiation therapy and chemotherapy, and in the development of clinically applicable microwave, radiofrequency, ultrasound and thermometry equipment. Numerous uncontrolled trials have suggested strongly that hyperthermia in conjunction with radiation therapy or chemotherapy may contribute to improved local control rates for recurrent or metastatic cancer without excessive morbidity. Carefully designed and well-controlled site and disease-specific prospective randomized trials with standardized hyperthermia and radiation therapy techniques, adequate thermometry, precise end points for tumour control and normal tissue toxicity are now essential to establish the role of hyperthermia in cancer management. Criteria for tumour site selection will be explored for trials employing radiation therapy and local-regional hyperthermia. Examples of sites selected will be presented which represent areas that can, with current technology, usually be adequately heated, and in which significant patient benefit may result from improved local-regional control.

Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology

“…Nevertheless, the quality of the heating is of the same magnitude as that described in previous studies where these parameters have been recorded [9,30]. The philosophy behind the European Society for Hyperthermic Oncology's clinical trials [8,12] has been to challenge the heating techniques which in previous non-controlled studies have indicated a potential benefit [4,6] in a phase III randomized study. Certainly, such policy has its shortcomings, but rather than continuing to optimize the heating ability while constantly being subjected to uncontrolled claims of efficiency, we have felt a need for conducting a randomized trial which would evaluate the clinical ability of the current heating equipment.…”

“…This is an illustration of the problems with hyperthermic oncology [8,[6][7][8]5], namely that rather than to perform a joint effort in making a proper evaluation of this biologically promising modality, many institutions conduct their activities independently, which in general has led to nonconclusive results. It is our hope that the current results in addition to its clinical results also will be recognized for demonstrating the usefulness of international collaboration.…”

“…Furthermore, these early clinical studies have indicated that a significant improvement in local control could be obtained without increasing normal tissue morbidity if either a relatively long interval between the two modalities was allowed for or if the tumours were heated (semi)selectively. From the early studies it appeared that especially three tumour sites have been the subject of combined heat and radiation therapy, namely advanced neck nodes, recurrent or advanced breast tumours, and malignant melanoma [5,8,9,10,11,3,12]. Part of the reason for this was the superficial nature of these tumours, but accumulating evidence from early clinical trials indicates that a significant improvement in local control was likely to be obtained without increasing normal tissue morbidity.…”

A role for the copper transporter Ctr1 in the synergistic interaction between hyperthermia and cisplatin treatment

“…In 1986, Kapp authored a review on the types of cancer that, based on lesion location and potential progression, would benefit from hyperthermia [35]. Based on mortality statistics, the author reported that local failures contribute to death in a high proportion of patients with brain, ovarian, prostate, cervical, oesophageal, bladder, and head and neck cancers.…”

Use of the Succinate Dehydrogenase Inhibition Test in Assessing the Heat Sensitivity of Tumor Cells

“…2|. However, hyperthermia is not effective for all tumors, since sensitivity to hyper thermia varies between tumors, as do chemosensitivity and radiosensitivity [3,4]. Hyperthermia also has effects on normal tissues adjacent to the treated tumor or.…”