Clinical InstrumentationRequirementswith a Reviewof the Perth Hyperthermia Experienci'

The problems of precise clinical thermometry are enormous, and, because the degree of sensitization to ionizing radiation is strongly dependent on temperature and time at temperature, it is important that this problem be solved in a practical way. In lieu of accurate temperature-recording methods, it is imperative that any clinical treatment regimens which utilize heating be with temperatures which are elevated only moderately (to per haps a maximum of 41 °C). With external heating methods, tumors with sluggish blood flow can be heated to a greater degree than normal tissues. This should be particularly true for hypoxic foci which are at some distance from cooling capillaries. Unfortunately, it seems unlikely that practical detectors can be designed to measure the temperatures of these crucial microenvironments. Hence, this is another reason why it may be necessary to be cautiously empirical about certain aspects of clinical treatment ap proaches utilizing hyperthermia. J. A. G. Holt and A. J. M. Nelson's experience in 52 patients with head and neck cancer treated with 434 MHz microwave hyperthermia and ionizing irradiation in Perth, Western Aus tralia, was reviewed during my visit there in the spring of 1978. The two-year disease-free survival of 47% for patients with advanced disease (T3, T4 or N2, N3) is promising. This is especially encouraging since these results were obtained with lower than conventional doses of irradiation and normal tissue tolerance was excellent. Phase I and II studies in this country appear warranted. As an introductory remark, it perhaps would be prudent to state that presently available radiobiological information mdi cates that we should not be able to cure a human epithelial cancer, 1 cm in diameter, with ionizing radiation. This is rn portant background because, if radiobiologists insist that we understand all the whys and wherefores of hyperthermia ex perimentally before it is used clinically, we may experience an inordinate delay in initiating a potentially useful modality into clinical practice. Incomplete understanding of the laboratory findings may continually put us off from doing something clini cally useful with patients. This is said somewhat with tongue in cheek, but at the same time seriously to remind us that it is probably not unreasonable to proceed cautiously now with a combined approach (moderate hyperthermia in conjunction with irradiation and/or chemotherapy) in suitable patients with advanced cancer. 1 Presented at the Conference on Hyperthermia in Cancer Treatment, Septam ber 15 and 16, 1978, Sen Diego, Calif. Supported in part by the National Cancer Institute, Wisconsin Clinical Cancer Canter Grant, Multidisciplinary Program in Radiation Oncology, 5-PO1-CA-i 9278-03. 2332 I am scheduled to discuss clinical instrumentation require ments. Let me say in advance that I do not anticipate that the situation will be clarified much by my presentation, and perhaps my presentation is not supposed to be clarifying. I may raise more questions, hopefully important ones, than I answer. The necessity for recording both temperature and time at temperature of normal tissues and tumors whenever possible will not be reviewed. Of course, precise thermometry is espe cially important for some normal tissues (brain, liver, and heart, for example) which cannot tolerate prolonged exposures to temperatures which exceed 42°C(6, 8). But precise thermo metry is not a trivial problem. In fact, the difficulties in accu rately determining temperature, particularly in deep-seated tissues and tumors, are enormous. The tomographic thermo metry technique, described by Christensen in this workshop (1), is an interesting approach and development. However, for these displays to be clinically useful, they undoubtedly will need to be 3-dimensional. This requirement compounds the reconstruction problem immensely. At more moderate temper atures, 41 .5°Cor less, precise thermometry is perhaps not so critical, since normal tissues tolerate this degree of hyperther mia well. So, the practical requirements for clinical thermometry will depend on the temperature to be utilized. Except for heating of extremities by perfusion, uniform heat ing of volumes composed of heterogeneous normal tissues and tumors is unlikely to be achieved other than by whole-body heating techniques; since the temperature of normal tissues and tumors approximates that of blood, thermometry is rela tively easy. But blood temperature must be closely monitored because with whole-body heating temperatures above 41.8— 42°C are hazardous and, in fact, may be fatal. Nevertheless, this temperature is not high enough to consistently completely eradicate tumors, even with heating episodes lasting 2 to 3 hr (6, 8). Therefore, to be more effective, in most clinical situations whole-body hyperthermia will be used in conjunction with chemotherapy. With regional perfusion, uniform temperatures of 40—41 .5°Ccan be achieved for up to 2.5 hr without causing important normal tissue injury (10). Better results accrue when chemotherapy and/or ionizing radiation is used in conjunction with the perfusion. For regional or localized hyperthermia using the extrinsic heating methods listed in Table 1, uniform heating is not possible. A practical method of more uniformly heating to moderate temperatures with minimal morbidity, to be used in conjunction with ionizing irradiation, is sought. Perhaps the radio frequency heating system discussed in this workshop by Storm will be a practical approach (12). Careful thermometry will be necessary to assure that normal tissue tolerance is not exceeded. Tumor temperatures also will need to be deter mined. With electromagnetic wave or ultrasound heating, tempera CANCERRESEARCHVOL. 39 on April 14, 2017. © 1979 American Association for Cancer Research. cancerres.aacrjournals.org Downloaded from Clinical Instrumentation Requirements