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PubMed1984

Regional hyperthermia in the treatment of clinically advanced, deep seated malignancy: results of a pilot study employing an annular array applicator.

From October 1980 through December 1982, 46 patients were entered into a pilot study at the University of Utah Medical Center to assess the feasibility and safety of heating deep-seated, advanced, pelvic and abdominal malignancies with an annular array of electromagnetic wave (EMW) applicators. The patients, most of whom were heavily pretreated, were treated on a protocol in which most of the patients received combined hyperthermia and low dose X ray therapy. Discomforting local symptoms were the predominant treatment related acute side effects in 28 patients with pelvic disease, while systemic hyperthermia and associated symptoms were the predominant side effects in 18 patients with abdominal disease. Minor subacute toxicity was minimal and no serious treatment related, chronic toxicity was observed. The treatments of 22 patients with sufficiently detailed thermometry were analyzed at arbitrary index temperatures of 41 degrees C and 43 degrees C. Objective response rates in 22 evaluable patients were 67% and 9% for pelvic and abdominal sites respectively.

Abdominal Neoplasms↗
PubMed1985

Temperature measurements in high thermal gradients: I. The effects of conduction.

Two temperature probes (a fluoroptic sensor and a metallic thermistor), which are both suitable for stereotaxic implantation, were used in comparative thermometry studies during interstitial microwave heating of the brain in vivo. Thermal distributions having large temperature gradients (5-10 degrees C/cm) were routinely observed. The temperature differentials (delta T) between the 2 probes were position dependent within the thermal field. The maximum difference in temperatures measured, using the 2 probes along identical tracks without a catheter, ranged between 0.5 degree C and 1.8 degree C. Near the brain/air surface, the thermistor measured lower temperatures than the optical probe; however, medial to the antenna, the thermistor temperatures were higher than the optic sensor. The measured temperature discrepancies are the result of smearing due to thermal conduction along the axial length of the metallic thermistor probe. These effects are significantly accentuated when the temperature probes are tracked in catheters. Experiments performed in a nonperfused phantom, heated with the interstitial microwave antenna, demonstrated similar conductive effects. Studies in a nonelectromagnetic environment (flow cell-thermal step gradient) additionally confirmed that thermal conductive artifacts were the major source of temperature error.

Animals↗
PubMed1985

Thermal distributions in a water bath heated mouse tumor.

In the past several years numerous investigators have employed various mouse tumor systems and a variety of heating methods to examine the effects of hyperthermia in vivo. These studies have led, in some cases, to different results in tumor response in what appear to be similar experiments. Our results indicate that these discrepancies may in part be attributable to variations in intratumor temperature and depend strongly upon the method and conditions of heating employed. In all cases, we have employed the C3H mammary carcinoma tumor system with the tumor implanted in the right hind limb of the mouse. All tumors were 7-9 mm in diameter at the time of the experiments. Water bath heating was employed with the animals under one of four possible conditions: the presence or absence of anesthesia, and the use or lack of core cooling. Thermometry was performed with an array of multiple microthermocouples, each less than 150 micron in diameter, implanted in the tumor in a grid-like pattern. Significant variations (1.0 degrees C for no anesthesia, p less than .01; 1.3 degrees C for Thorazine/Ketamine, p less than .001) in intratumor temperature were found across the tumor in the unperturbed state. These variations were essentially eliminated under all hyperthermic conditions. Control of core (rectal) temperature (with or without anesthesia) reduced the intratumor temperatures even though the water bath temperature was held constant resulting in variations between water bath and tumor temperatures of from 0.1-0.8 degrees C.

Animals↗
PubMed1985

A comparison of deep regional hyperthermia from an annular array and a concentric coil in the same patients.

Twenty-two patients with advanced pelvic or abdominal malignancy (or both) were treated on successive occasions with hyperthermia produced by an annular array (AA) (60-80 MHz, 500-1800 W forward power) and a concentric coil (CC) (13.56 MHz, 350-1000 W forward power). Both devices were compared with respect to acute toxicity and power limitations. There was no power limiting factor in pelvic heating in 7/14 patients treated with the AA, however 13/14 experienced power limiting sacrococcygeal pain with the CC. The 9 patients who underwent abdominal heating had a variety of power limitations with both devices. Thermal mapping was performed in 23 treatments with the AA and in 19 with the CC. Composite thermal maps of patients with similar thermometry sites show that heating patterns produced by the CC were predictable from theory and static phantom measurements. The AA achieved broader regional heating, particularly at depth, but heating patterns were less predictable. Spatial thermal dose (TD) analysis revealed higher minimum tumor TDs and more favorable mean tumor/normal tissue TD ratios with the AA than with the CC. We conclude that the AA is superior to the CC for pelvic treatment and that both devices have limitations in abdominal treatment.

Abdominal Neoplasms↗
PubMed1987

Automated temperature scanning for hyperthermia treatment monitoring.

Ideal descriptors of hyperthermia treatments will most likely depend on complete target temperature distributions. Although these distributions can be modeled numerically, the accuracy of models is limited by the sparseness of temperatures measured in vivo. Thus, the strategy of monitoring temperatures may play a key role in improving hyperthermia therapy. Scanning temperatures by manual translations of thermometers was found to be excessively time consuming. Consequently an automated system was developed consisting of linear actuators, outriggers, guide tubes, thermometry catheters, personal computer, and dedicated hardware and software. During treatments, scan patterns were created with algorithms using temperatures measured preceding each thermometer translation. Measurement position had a noteworthy influence on thermal dose estimated by current models. Relative to manual scanning, automated scanning increased measurement efficiency, reduced probe position uncertainty, reduced operator time, and provided improved data for modeling bioheat transfer and thermal dose.

Algorithms↗
PubMed1988

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.

Brain Neoplasms↗
PubMed1989

Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a Report by the Radiation Therapy Oncology Group.

Since February 1981, 300 patients with superficial measurable tumors were randomized on an RTOG protocol (81-04) involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (42.5 degrees C, 60 min). This is a report of 218 eligible patients with single lesions: 107 treated with radiotherapy alone (RT), 111 with radiotherapy plus hyperthermia (RT + HT). Only 56% of the 24 tumors less than 3 cm and 36% of the 53 lesions larger than 3 cm received what was felt to be "adequate" therapy (greater than or equal to 29 Gy and 8 heating sessions). Overall complete response (CR) was observed in 28% of the patients treated with RT, and 32% of the patients receiving RT and heat. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In the head and neck tumors less than 3 cm in diameter there was no difference in CR with irradiation alone or combined with hyperthermia (46% vs 43%). However, in the breast, and trunk and extremities a better CR rate was noted with irradiation and heat (55% and 67%) than with irradiation alone (33% and 0). In lesions less than 3 cm treated with irradiation and heat the probability of remaining in response was 80% compared with 15% with irradiation alone. In lesions larger than 3 cm no difference in CR was observed in either treatment group. It has been hypothesized that the response rate is higher in patients with smaller lesions (less than 3 cm) and in breast/chest wall, trunk/extremity lesions because these tumors and anatomical sites are easier to heat adequately. Problems encountered in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to accurately represent the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because of short survival of some patients and occasionally rapid tumor regression that may cause necrosis which may be misinterpreted as persistent tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Phase I/II study, combination of radiotherapy and hyperthermia in patients with deep-seated malignant tumors: report of a pilot study by the Radiation Therapy Oncology Group.

This is a report of a Phase I/II study activated in March 1984 and completed in October 1988 by the Radiation Therapy Oncology Group on the feasibility/toxicity of hyperthermia in patients with deep-seated malignant tumors. The main objective of this study was to evaluate the morbidity of regional hyperthermia (systemic and regional, acute and late effects); a secondary objective was to evaluate tumor response to combined irradiation and regional hyperthermia. A total of 54 patients with locally advanced abdominal or pelvic malignancy were accrued to this study; 42% were male and 58% female. Seventy-five of the patients had pelvic tumors and 25% abdominal tumors. Acute toxicities included grade 4 in three patients (1 cutaneous, 1 infection and 1 chemical peritonitis) one grade 3 (skin), and 12 grade 2 toxicities (6 skin and 6 gastrointestinal). With regard to late toxicities, grade 4 was noted in one patient (skin), grade 3 (GI) in one, and grade 2 (skin, peripheral neuropathy) in six patients. The prescribed course of hyperthermia was completed in 17 (32%) of patients. In 36 patients (68%) the course of hyperthermia was terminated, primarily because of patient discomfort. Tumor response was assessed by physical examination or radiological studies. Of 44 patients evaluable for response, there were 17 (39%) complete responses and 6 (14%) partial responders. Significant technical problems in heat delivery and thermometry remain.

Abdominal Neoplasms↗
PubMed1991

RTOG quality assurance guidelines for interstitial hyperthermia.

This document specifies the current recommendations for quality assurance for hyperthermia administration with interstitial techniques as specified by the Radiation Therapy Oncology Group (RTOG). The document begins by providing a brief description of the physical principles behind the use of the three most commonly used methods of interstitial hyperthermia: radiofrequency (RF-LCF), microwave antennas, and ferromagnetic seeds. Emphasis is placed on features that effect quality assurance. Specific recommendations are provided for: a) Pretreatment planning and equipment performance checks, b) Implant considerations and documentation, c) Thermometry, and d) Safety procedures. Specific details regarding quality assurance issues that are common to all local and regional hyperthermia methods are outlined in previous documents sponsored by the RTOG. It is anticipated that technological advances may lead to future modifications of this document.

Documentation↗
PubMed1992

Relationships among tumor temperature, treatment time, and histopathological outcome using preoperative hyperthermia with radiation in soft tissue sarcomas.

The lack of an unambiguous thermal dosimetry continues to impede progress in clinical hyperthermia. In an attempt to define better this dosimetry, a model based on the cumulative minutes during which arbitrary percentages of measured tumor temperature points exceeded an index temperature was tested in patients with soft tissue sarcomas treated with preoperative hyperthermia and conventional radiation therapy. Patients received 5000-5040 cGy at 180-200 cGy per fraction. Hyperthermia was delivered 30-60 minutes after radiation therapy and given for 60 minutes. Patients were randomized between one and two hyperthermia treatments per week for a total of five or 10 treatments, respectively. Lesions were excised 4-6 weeks after completion of hyperthermia/radiation therapy. Successful treatment outcome was considered to be the finding of greater than 80% necrosis of the sarcoma upon histopathologic examination of the resected specimen. Forty-five patients were eligible with thermometry data available in 44 patients. An average of 19 interstitial sites were monitored each treatment per tumor. Sixty percent of tumors had a successful histopathologic outcome. Univariate analysis demonstrated that several descriptors of the temperature distribution were strongly related to treatment outcome; more strongly than nonthermometric factors, such as the number of treatments per week, tumor volume and patient age and more strongly than the commonly used temperature descriptors Tmin and Tmax. Descriptors that incorporated both temperature and time were also superior to the more commonly used descriptors Tmin and Tmax. Multivariate stepwise logistic regression analysis revealed that a descriptor of both the hyperthermia treatment time and the frequency distribution of intratumoral temperatures was the strongest predictor of histopathologic outcome and that the best predictive model combined this time/temperature descriptor and one versus two treatment per week grouping. The more conventional temperature descriptor, minimum measured tumor temperature, did not significantly enhance the predictive power of treatment group. Based on these results, we recommend that descriptors based on both the frequency distribution of intratumoral temperatures and hyperthermia treatment time be tested for relationships with treatment outcome in other clinical data bases. Furthermore, we recommend that temperature descriptors that are less sensitive to catheter placement and tumor boundary identification than Tmin and Tmax (such as T90, T50, and T10) be tested prospectively along with other important thermal variables in Phase II trials in further efforts to define a thermal dosimetry for spatially nonuniform temperature distributions.

Combined Modality Therapy↗
PubMed1992

Three-dimensional theoretical temperature distributions produced by 915 MHz dipole antenna arrays with varying insertion depths in muscle tissue.

Interstitial microwave antenna array hyperthermia (IMAAH) systems are currently being used in the treatment of cancer. The insertion depth of an interstitial microwave antenna, defined as the length of the antenna from the tip to the point of insertion in tissue, affects its ability to produce uniform power deposition patterns in tumor volumes. The effect of varying insertion depths on the ability of an IMAAH system to heat two theoretical tumor models was examined. Four dipole microwave antennas were implanted in a 2 x 2 cm array and driven at 915 MHz in muscle tissue. The explicit power deposition patterns were calculated for each insertion depth using known theory. The bioheat transfer equation was solved for the 3-dimensional steady-state temperature distributions in cylindrical and ellipsoidal tumor models using a finite element method. Homogeneous and nonhomogeneous blood flow models were considered. As a basis of comparison of the various temperature distributions, the volume of tumor heated to greater than or equal to 43 degrees C was calculated. Under the conditions of this study, the insertion depth was shown to have a significant effect on the ability of an IMAAH system to heat the tumor volumes. A sharp decrease in the percentage of tumor volume heated to greater than or equal to 43 degrees C was seen for insertion depths between 7.8 and 14.6 cm. At an insertion depth of 11.7 cm (3/4 lambda) there was virtually no heating of the tumor. Regions of elevated power occurred outside of the desired treatment volume, stressing the importance of adequate thermometry techniques and demonstrating the need for hyperthermia treatment planning prior to implantation of an antenna array. Plots of the power deposition patterns and the corresponding temperatures produced in the diagonal plane of the antenna arrays are present.

Equipment Design↗
PubMed1993

Feasibility and toxicity of transrectal ultrasound hyperthermia in the treatment of locally advanced adenocarcinoma of the prostate.

PURPOSE: This Phase I trial tests the ability of a new hyperthermia device, the transrectal ultrasound probe, to heat the prostate gland, and evaluates the toxicity of transrectal ultrasound hyperthermia (TRUSH) given with concurrent standard external beam irradiation in the treatment of locally-advanced adenocarcinoma of the prostate. METHODS AND MATERIALS: Between June, 1990 and August, 1991, 14 patients with American Urological Society Stage C2 or D1 adenocarcinoma of the prostate were treated with TRUSH concurrently with standard external beam radiotherapy to the prostate. Twenty-two heat treatments were delivered in 14 patients; 8 patients received two TRUSH procedures, each separated by 1 week. Patient age ranged between 53-86 (mean: 72) years. Three patients had well-, 6 patients had moderately-, and 5 patients had poorly-differentiated adenocarcinoma of the prostate. Karnofsky status ranged from 70-90. Standard radiotherapy to the prostate and periprostatic tissues was delivered using a four-field approach with 1.8-2 Gy daily fractions delivered 5 x/week to a total dose of 67-70 Gy calculated to the minimum tumor volume. TRUSH was delivered after transperineal placement of multipoint thermometry probes by a urologist, under transrectal ultrasound guidance. Two to three thermocouple probes containing seven sensors each were placed in the prostate in an attempt to sample temperatures throughout the gland. The sensor depth from the rectal wall ranged from 5-25 mm. RESULTS: Thirty-six percent of all sensors were heated above 42.5 degrees C averaged over 30 min; and all patients had at least some sensors within the prostate heated to temperatures > or = 42.5 degrees C. The average temperature of all sensors of all sensors (T(ave) +/- s.d.) over all treatments, however, was only 41.9 degrees C +/- 0.9 degrees C over 30 min. The maximum temperature for normal tissues outside the gland was 41.1 degrees C +/- 1.3 degrees C. Treatments have been well-tolerated with few complications. Tolerance has been "good" in 17/22, "fair" in 3/22, and "treatment limiting" in 2/22 treatments secondary to position intolerance and/or pain. There has been one episode of hypotension related to narcotic administration and three episodes of rapidly resolving pain during hyperthermia treatment. Mild hematuria has occurred in 5/22, and moderate hematuria has occurred in 2/22 transperineal thermometer catheter placements. CONCLUSION: In conclusion, TRUSH is well-tolerated and has great potential for consistently heating the prostate gland. We anticipate that further equipment modifications will improve our ability to heat the entire prostate to temperatures > 42.5 degrees C.

Adenocarcinoma↗
PubMed1993

Cumulative minutes with T90 greater than Tempindex is predictive of response of superficial malignancies to hyperthermia and radiation.

PURPOSE: To better define thermal parameters related to tumor response in superficial malignancies treated with combined hyperthermia and radiation therapy. METHODS AND MATERIALS: Patients were randomized to receive one or two hyperthermia treatments per week with hyperthermia given during each week of irradiation. Hyperthermia was given for 60 min with treatments begun within 1 hr following irradiation. Power was increased to patient tolerance or normal tissue temperature of 43.0 degrees C. Irradiation was generally given 5 times per week with doses prescribed to normal tissue tolerance (generally 24-70 Gy at 1.8-2.5 Gy per fraction). Multipoint thermometry was used with temperatures obtained every 5 min. RESULTS: One hundred eleven individual treatment fields containing 1 or more tumor nodules were completely evaluable. The complete and overall response rates were 46% and 80%, respectively. Forty-one percent of all treatment fields (51% of responding lesions) remained controlled at 2 years. Multivariate analysis revealed that the cumulative minutes that the temperature achieved by 90% of the measured tumor sites (T90) was > or = 40.0 degrees C, tumor histology, tumor volume, and radiation dose were significantly associated with complete tumor response. The complete response rate was not significantly affected by the number of hyperthermia treatments given per week. The incidence of clinically significant complications was low. CONCLUSIONS: These results support the usefulness of the cumulative minute system in describing time-temperature relationships. The significance of thermal variables with regard to tumor response strongly supports the contention that hyperthermia can be a useful adjunct to irradiation for the local control of cancer.

Adult↗
PubMed1993

Interstitial thermoradiotherapy with ferromagnetic implants for locally advanced and recurrent neoplasms.

PURPOSE: The University of Arizona, University of California at San Francisco, City of Hope Medical Center, and University of Wisconsin participated in a Phase I/II protocol to assess the heating ability and the toxicity of interstitial thermoradiotherapy using ferromagnetic implantation. METHODS AND MATERIALS: Forty-four patients with advanced primary or recurrent extra-cranial solid malignancies were enrolled in this study. Fourteen gauge catheters were implanted into tumors and, once in the department of Radiation Oncology, loaded with ferromagnetic seeds to deliver a 60 min hyperthermia treatment. Multi-point thermometry was continuously used throughout the heating sessions for all patients, sampling the periphery as well as the core of the tumor. After 192Iridium brachytherapy, 18 patients then had an additional treatment. The mean radiation dose while on protocol was 50.0 Gy, with total doses (including prior radiotherapy) ranging from 20.3-151.8 Gy (median = 88.7 Gy). Response and toxicity were assessed by inspection, palpation, and/or radiologic studies. Forty-one patients were evaluable for response, and there were 55 analyzable hyperthermia treatment sessions. RESULTS: The complete response rate was 61% (25/41). The partial response rate was 31.7% and only 7.3% failed to respond. Median duration of local control has not yet been reached. The mean maximum, minimum, and mean time-averaged temperatures for all in-tissue sensors were 43.7 degrees C, 38.7 degrees C, and 41.0 degrees C, respectively. Tumor size was the only factor significantly correlated with temperatures or with complete response rate; larger tumors attained higher temperatures but smaller tumors had a higher response probability. Nineteen patients (43%) experienced toxicities, however there was only a 7% (3/44) rate of serious complications (Grade 3 or 4). Prior treatment with hyperthermia was the only factor significantly correlated with serious toxicity. CONCLUSION: These results, a 93% total response with only 7% serious toxicity, are encouraging especially in the context of the patient population treated. Phase II/III studies involving ferromagnetic implantation are warranted.

Adult↗
PubMed1995

Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy: results of a phase I/II study.

PURPOSE: Since 1985, the University of Minnesota Hospital and Clinic has investigated the efficacy and safety of 8 MHz radiofrequency (RF) capacitive hyperthermia using the Thermotron RF-8. This study reports the thermometric and clinical results of 119 patients treated with RF hyperthermia in combination with radiotherapy (RT). METHODS AND MATERIALS: Of 119 patients, 69 received high-dose RT and 50 patients received low-dose RT because of previous irradiation to the treatment site. The most common anatomic sites treated were within the pelvic cavity or head and neck area. Thirty-three percent and 24% of tumors treated were > 7 cm and > 10 cm in largest diameter, respectively. Forty percent of the patients had deep-seated tumors (depth > 6 cm). Hyperthermia was given as soon as possible after RT twice weekly, allowing at least 72 h between treatments. The objective was to raise intratumoral temperatures to 42-43 degrees C or above for 30-50 min while keeping normal tissue temperatures below 40-41 degrees C. RESULTS: Of 119 patients, 40% achieved a Tmax tumor temperature of > 42 degrees C and 40% achieved 40-42 degrees C Tmax. Higher Tmax) tumor temperatures were observed as tumor size increased. Tumors > 10 cm in largest diameter had a Tmax of 42.2 degrees C. Tumor depth was not a significant factor for the tumor temperatures achieved. Of 119 patients, 11% achieved complete response and 38% achieved partial response. Of the no-response patients, 34% had symptomatic palliation and 15% had stable disease for at least 12 months after treatment. We were able to treat tumors of patients with subcutaneous fat as thick as 3 cm by precooling the fat for 20 min with 10-15 degrees C saline-filled boluses prior to the initiation of heating. During treatment, 60% of patients complained of varying degrees of pain and 19% had pain that was a factor in limiting treatment. Vital signs were relatively stable and not a factor in limiting treatment. CONCLUSION: The Thermotron RF-8 is a useful hyperthermia device that can raise tumor temperatures to a therapeutic level (i.e., 42 degrees C) in a significant proportion of patients with superficial, subsurface, and deep-seated tumors, with minimal adverse effects, complications, and systemic stress. Further clinical studies using improved thermometry systems are warranted.

Adenocarcinoma↗
PubMed1994

HSP 70 synthesis in clinical hyperthermia patients: preliminary results of a new technique.

PURPOSE: Although thermotolerance may be an important variable in clinical hyperthermia, few means have been described to measure its effect or duration in the clinical setting. This study was undertaken to determine if heat shock protein 70 could be used as an assay to predict the presence of retained thermotolerance in human tumors. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing hyperthermia and assayed for heat shock protein 70 synthesis. Eight patients having advanced, persistent, or recurrent malignant tumors had open-ended thermometry catheters placed into the lesion being heated. Through these catheters, tissue samples were obtained using a fine needle aspiration technique. Attempts were made to obtain samples before and after the first three heat treatments. Some samples were labeled immediately with radioactive methionine (35S) at 37 degrees C for 4-8 hr, others were given a test heat dose in vitro and then labeled. Protein synthesis profiles were analyzed by gel electrophoresis and autoradiography. RESULTS: Preliminary results show that it is possible to obtain tissue from hyperthermia patients in a safe and practical manner, that the rate of heat shock protein 70 synthesis can be measured in a variety of tumors, and that the persistence of thermotolerance in the clinical setting can be shown by the inability to reinduce heat shock protein 70 synthesis. CONCLUSION: The measurement of heat shock protein 70 using the described technique may provide an assay for retained thermotolerance in clinical hyperthermia. Technical difficulties which need to be addressed include obtaining sufficient tissue in all patients, confirming the presence of tumor in the obtained tissue, and obtaining tissue at more frequent intervals to best determine the kinetics of thermotolerance.

Aged↗
PubMed1994

Interstitial hyperthermia and high dose rate brachytherapy in the treatment of anal cancer: a phase I/II study.

PURPOSE: The rate of local failure is sufficiently high following sphincter conserving surgery and radiation therapy for advanced anal cancers to warrant investigation of improved local treatment techniques. This Phase I/II study was undertaken to investigate the site-specific toxicities and response of Stage II and III anal cancers to interstitial thermoradiotherapy using a hot water interstitial system. METHODS AND MATERIALS: Between September 1988 and March 1991, 14 patients with primary carcinomas of the anal canal, UICC Stage T2-3, N0-1, M0, were treated with split-course external beam irradiation to the pelvis (30 Gy + 20 Gy) and 1 or 2 interstitial Iridium-192 high dose rate (Ir-192 HDR) implants (6-8 Gy each) immediately followed by interstitial hyperthermia (HT). Patients with tumor diameters > 3 cm were scheduled to receive chemotherapy consisting of 2 courses of 5-fluorouracil and mitomycin C given concomitantly with external beam radiation. Interstitial hyperthermia was induced by circulating warm water through the needles that were implanted to hold the Ir-192 source. The treatment goal was to achieve and maintain a temperature of 42.5 degrees C over a time period of 40 min. A 3-point thermocouple probe inserted into one or two additional needles was used for thermometry. The temperatures were recorded by manual mapping along these needles at steps of 0.5 or 1 cm. RESULTS: A total of 20 Ir-192 HDR-HT implants were performed in 14 patients. All but two patients completed the external beam irradiation; five patients received concomitant chemotherapy. Analysis of thermal parameters showed that minimum intratumoral temperatures (Tmin) of 42 degrees C, 42.5 degrees C, 43 degrees C, and 44 degrees C were achieved in 64%, 37.5%, 14%, and 7% of patients, respectively. Intratumoral mean Tmin, mean average, and mean maximum temperatures for these patients were 41.7 degrees C, 42.4 degrees C, and 43.4 degrees C, respectively. Brachytherapy and HT were well tolerated. Clinical complete responses (cCR) were obtained in 11/14 (78.5%) patients, complete histopathological responses (pCR) in 10/14 (71%). Only one patient with pCR recurred and succumbed to her disease. Patients with persistent disease (1 minimal and 3 partial responders, including 1 cCR) underwent abdominal-perineal resection but subsequently died from local-regional recurrence. One patient with pCR died from unrelated causes. Median survival for all patients from onset of radiation to death or last follow-up is 26 months. Eight patients are alive disease-free after a follow-up ranging from 16-44 months (median: 30, mean: 30 months). Treatment complications were limited to two patients who developed persistent ulcers. Sphincter function was maintained in 50% of patients. CONCLUSION: This study demonstrates that interstitial warm water hyperthermia in combination with brachytherapy for anal carcinomas is feasible and did not add to complications when compared to studies employing external beam irradiation and brachytherapy alone. The thermal parameters obtained by the warm water system compare favorably to those reported by others using radiofrequency and microwave systems.

Adult↗
PubMed1994

Clinical hyperthermia with a new device: the current sheet applicator.

PURPOSE: The current sheet applicator (CSA) is a newly developed microwave hyperthermia device. Advantages over commercial microwave applicators include its small size and high ratio of heating area to physical aperture area. These physical characteristics make the CSA excellent for heating constricted areas and allow the use of arrays of CSAs over large surfaces. This study examines the clinical efficacy of the CSA for heating superficial malignant tumors. METHODS AND MATERIALS: From December 1989 through October 1991, 19 patients with recurrent or metastatic superficial malignant tumors were treated once or twice weekly to 30 hyperthermia fields using one to four CSAs. Each field received from one to four hyperthermia treatments for a total of 74 treatments. The treatment objective was to elevate the tumor temperature to a minimum of 42.5 degrees C for 30 min (2 patients) or 60 min (17 patients). Intratumor temperatures were measured with percutaneous fiberoptic thermometry probes. All patients received concurrent fractionated radiation therapy with total dose ranging from 20 to 65 Gy (median 46 Gy). Seventeen of the 30 fields had been previously irradiated to a median dose of 50 Gy. RESULTS: Mean values for the maximum temperature, average temperature, and minimum temperature were 43.6 degrees C +/- 1.0, 42.2 degrees C +/- 1.4, and 41.0 degrees C +/- 1.5, respectively. Mean values for T50 and T90 were 42.2 degrees C +/- 1.1 and 41.0 degrees C +/- 1.3, respectively. The overall response rate for all assessable fields was 96%. Only Only three responding tumors have progressed with a median follow-up period of 6 months. Treatment related morbidity was generally mild and self-limited. CONCLUSION: The CSA is a promising new microwave hyperthermia device capable of heating superficial tumors to therapeutic temperatures. When used in combination with radiotherapy, response rates are excellent without excessive toxicity.

Aged↗