Patterns of changes of tumour temperatures during clinical hyperthermia: implications for treatment planning, evaluation and control.

The patterns of changes in tumour temperatures were studied at selected times throughout 104 hyperthermia sessions. Temperature change patterns were analysed in the context of the known patterns of change of the applied power. First, of 69 extracranial treatments analysed, 74% indicated relatively flat temperatures at constant applied power during a major portion of the treatment, thereby indicating that during that time there were no major changes in any of the physical or physiological tissue parameters which contribute to the ability of the tumour tissue to remove energy (Pattern 1). Second, after reaching an initial steady state, approximately 14% of these extracranial treatments showed either steadily decreasing temperatures at constant power, or constant temperatures at steadily increasing applied power, thereby indicating that the tumour's ability to remove energy was steadily increasing in time following the initial steady state (Pattern 2). Finally, after reaching an initial steady state, the remaining 12% of these treatments showed a pronounced decrease in temperature occurring about 10-20 min into the treatment followed by increasing temperatures or levelling off of temperatures at a higher value than the temperature minimum that had occurred, all at constant applied power (Pattern 3). Of 35 brain treatments analysed, 80% followed Pattern 1, 14% followed Pattern 2, and 6% followed Pattern 3. Intratumoral heterogeneity was evident in some cases with approximately 44% of all treatments having at least one individual temperature sensor change in a manner that did not follow the average direction of change when all sensors were combined. For seven patients with permanent probes, the patterns of change presented in the first treatments were also observed during six out of seven of the second treatments. In addition, three out of the five patients who had an evaluable third treatment showed a pattern of change during that third treatment that was similar to the pattern observed in both treatment one and treatment two.

A phase I study of the toxicity of regional hyperthermia with systemic warming.

This study examines the consequences of allowing moderate systemic hyperthermia during regional heating of the abdomen and pelvis in 29 patients participating in Phase I studies of hyperthermia combined with chemotherapy or radiation therapy. In Group 1 (20 patients, 42 treatments), systemic temperatures were limited by employing surface cooling, while in Group 2 (9 patients, 24 treatments), surface warming and insulation were used so that systemic temperature would rise. Mean time-averaged oral temperatures were 38.4 degrees C and 39.9 degrees C for Groups 1 and 2, respectively. Time-averaged mean regional temperatures were 40.2 +/- 0.7 degrees C and 41.5 +/- 0.2 degrees C for Groups 1 and 2, respectively (p < .001). Regional temperatures > or = 41.0 degrees C were achieved by 64% of Group 1 and all Group 2 patients. The mean time-averaged power required was significantly lower for Group 2 (453 W vs 740 W; p = .032), as was the incidence of pain. Mean maximum pulse rate was significantly higher in Group 2, although this was not associated with symptoms. Allowing systemic temperature to rise decreased power requirements and treatment-related pain, at the cost of an asymptomatic increase in heart rate. The results suggest that regional heating may be more readily achieved in the setting of elevated systemic temperature.

Development of scanned focussed ultrasound hyperthermia: clinical response evaluation.

Selective heating of irregularly shaped tumors at depth can now be accomplished through focussing and controlled scanning of energy deposition patterns by ultrasound. A scanned focussed ultrasound (SFUS) hyperthermia system developed at the University of Arizona has been used to deliver 220 treatments to 87 tumors in 71 patients with extracranial malignancies between October 1986 and May 1990. Patients received an average of three SFUS hyperthermia treatments, spaced weekly, during ongoing fractionated radiotherapy. The most common anatomic sites treated were the pelvis (22 patients), chest wall or breast (14), neck (8), and axilla (7), while the most common histologies were adenocarcinoma (36), squamous cell carcinoma (11), and melanoma (10). Concurrent radiotherapy was delivered (range 1000-7640 cGy, mean 4320 cGy) to 67 SFUS hyperthermia patients; 4 received concomitant chemotherapy. Tumor volumes ranged from 1-2100 cubic centimeters (mean 325 cc), and 75% were located at depths greater than 3 cm from skin. A 62% overall response rate was observed, with 22% of treated tumors demonstrating a complete response (defined as complete disappearance of treated tumor), and 40% exhibiting a partial response (defined as greater than or equal to 50% reduction in tumor volume). Dramatic local pain reduction was achieved in 42% of the tumors treated. The acute tolerance of SFUS hyperthermia was quite good, and chronic toxicities (persistent skin blisters/burns) were identified in two patients. The versatility of the SFUS system is discussed, as well as its future potential for improving control of advanced loco-regional malignancies treated with curative intent.

The CDRH helix. A phase I clinical trial.

Seventeen patients have been given regional hyperthermia treatments using the Center for Devices and Radiologic Health (CDRH) Helix, a resonant helical coil unit. Most of these patients had large, clinically advanced tumors, whose mean volume exceeded 1000 cc. Mean maximum, minimum, and average temperatures were 40.6, 38.6, and 39.6 degrees C, respectively, for all sites combined. The pelvic heating capabilities of the CDRH Helix and the BSD-1000 annular phased array were compared, and generally were equivalent. Although the Helix could be used in a wider variety of locations, and was more comfortable and easier to use than the BSD-1000 annular phased array, neither device was particularly effective in generating clinically useful temperatures; the Helix is currently under investigation for use in regional-systemic hyperthermia in combination with antineoplastic drugs and biologic response modifiers.

Scanned focussed ultrasound hyperthermia: initial clinical results.

Between November 1986 and July, 1987, a preliminary study to determine the feasibility of scanned focussed ultrasound for clinical hyperthermia at various sites was conducted. Fourteen patient (17 tumors) have been treated using a microprocessor-controlled apparatus developed at the University of Arizona by modifying a commercially available diagnostic ultrasound unit. We have treated nine pelvic tumors, four extremity tumors, two brain tumors, and two extracranial head and neck tumors for a total of 42 treatments. Multipoint thermometry was achieved for all patients, with 2-25 (mean = 10) points monitored during each treatments within the scanned tumor volume. Average maximum temperature within the scanned tumor volume was 44.2, 44.7, 44.8, and 42.0 degrees C for pelvic, extremity brain, and extracranial head and neck tumors, respectively; similarly, 55%, 45%, 71%, and 0 of monitored points exceeded 42.5 degrees C. Pain limited applied power in 15 of 42 treatments, and bone pain with a periodicity similar to the scanning periodicity was seen in 11 treatments. A non-randomized comparison of temperatures achieved using scanned focussed ultrasound to those achieved using the microwave annular array and the CDRH Helix suggests that scanned focussed ultrasound may have promise and potential advantages in heating selected pelvic tumors.