Setembro de 1999
Marina Del Rey, Los Angeles, CA, USA.

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IMMUNO-THERAPEUTIC EFFECTS OF HYPERTHERMIA
Paolo PONTIGGIA °, Sergio BARNI *,
Vittorio BERTONE *, Elisabetta PONTIGGIA °
°Dept. of Hyperthermic Oncology, Casa di Cura Città di Pavia, 27100 Pavia, Italy
*Dept. of Animal Biology, University of Pavia ; Italy

Therapeutic hyperthermia (42-43°C at the target level) exerts its effects at different levels:

- increased temperature induces tumor cell destruction via an augmented need of nutrients. The poor vascular perfusion and the insufficient enzymatic activity of neoplastic cells impair the metabolic supply of tumors;

- the large majority of chemotherapeutic agents are sensible to heat

- immune reactivity of neoplastic patients is usually suppressed by the progression of disease or by the use of chemo- and/or radiotherapy.

Hyperthermia can enhance the immune reactivity in these patients stimulating the macrophagic function.

A macrophage lysosomal exocytosis induced by hyperthermia has been observed in cancer patients. This macrophagic activation proved to be characterized by ultrastructural changes in sevaral cases of human metastatic carcinoma and Kaposi’s sarcoma lesions before and after hyperthermic treatment at 42°C for 90 minutes.

Using transmission electron microscopy, we observed that hyperthermia caused the disappearance of cytoplamatic granules, with a consequent extracellular scavenger action by phagocytic cells and the proliferation of organelles such as mitochondria, endoplasmatic reticulum and Golgi complex most probably due to a subsequent restoration of the granular pool in the degranulated macrophages.

Here we confirm the basic immuno-stimulating activity of thermic treatment in a case of multiple myeloma with an extramedullary localization at the thorax level.

The electron microscopic examination showed:

- a direct anti tumor activity exerted by the radiofrequency therapy.

an indirect immunostimulation mediated by the macrophagic activation, already observed in several primary and metastatic tumors, that could be very important in the induction of favorable outcome in cancer patients.

EFFECT OF LOCAL HYPERTHERMIA COMBINED WITH TAXOL ON
MICE INOCULATED WITH U14 CARCINOMA CELLS
Sun Qian; Tianjin ; 2 nd. Central Hospital.; Tianjin, P. R. China
Gon Bai Qing.; Hospital of Qiqihar Rolling Works CO. LTD.; P. R. China

Taxol is the only medicine acted upon the microtubule. It’s effective for many cancers. hyperthermia is also the method for cancer treatment. In order to afford an optimum therapeutic results, an animal experiment has been studied by combining treatment of taxol and hyperthermia. 40 mice, female, with weight of 25-30g. each, were inoculated with U14 (a kind of cervical cancer cell) in the thigh. When the tumors grew up to about 1cm. in diameter, the mice were divided into 4 groups. The 1 st Group was control group without being treated. The 2 nd Group was treated with taxol (20mg/kg injected into the abdominal cavity). The 3 rd group was treated with microwave hyperthermotherapy apparatus of Model 2450Mhz at 44C for 30min. twice a weeks for only on week. The 4 th Group was treated by the methods employed in 2 nd And 3 rd group. The size of each tumor was measured every day from the beginning of the treatment. At 12 th Day after the treatment, the tumors were taken out of the thighs and sent for examination with optic and electronic microscopy. The results have been taken a statistical analysis and found that the tumor growth has an obviously depressing effect in the 4 th. Group then the other 3 groups. The changes of the examination with optic and electronic microscopy show that the damage of the tumor cells of the 4 th. Group also remarkable then the other 3 groups. It is found that hyperthermia can add to the effect of mere treatment with taxol, and the combined effect is even better than that it was treated by hyperthermia and taxol solitarily. There are 3 tables and 12 photos to discuss in detail.

COMET/UFO
Shidnia, H.
Indiana University & University Heights Cancer Center
Indianapolis , Indiana , USA

The author will share with you his experience of 25 years of practice in Hyperthermia at one institution, in over 500 patients and 3000 Hyperthermia sessions.

The author will discuss the effect of:

Hyperthermia on normal and malignant cells.

The timing of Hyperthermia in regard to radiation therapy.

Effect of local and w.b .Hyperthermia on tumors and also the immune system.

Effect of combined local Hyperthermia and radiation on "so called" radio resistant tumors and radiation failure ( 2 nd or 3 rd recurrence ) malignant melanoma, etc.

The following table above is the result of hyperthermia and radiation therapy at

Indiana University and University Heights Cancer Center

Indiana University & University Heights Cancer Center Hyperthermia Treatment Involving 456 Anatomical Sites (97 patients) from April 1987 through October 1994

Results of Treatment with Hyperthermia and Radiation Therapy (1987-1992)

CLINICAL EXPERIENCE WITH HYPERTHERMIA
(WHOLE BODY, REGIONAL AND LOCAL HYPERTHERMIA)
David G. Spall, M.D., M.A., D.D.R.
Queensland Prostcare and Cancer Clinic; Brisbane , Australia

The Queensland Prostcare and Cancer Clinic has four systems of inducing Hyperthermia and Prostcare Thermotherapy.

This illustrated presentation is a review of clinical experience using Whole Body Hyperthermia utilizing the Heckel Tent ( Heckel , Germany ). Heat is generated by reflected energy from an array of infrared tubes. Core temperature is measured with either oesophageal or rectal temperature measurement. Temperatures up to 42° C are obtainable in selected patients. Most patients have sustained core temperatures 39° - 41° C for several hours.

Regional Microwave (434 Mhz) induced Hyperthermia (Microwave Therapy) is by means of a BST 2500 phased pentacular array into the moving treatment field. This is preceded by the bolus injection of an analogue of L Cystein, precipitating excitation within the glutathione cycle. Reference will be made to the pioneering work of Dr. J. A. G. Holt, et al. in this field.

Local Hyperthermia induced by 300 Mhz, from two separate and columnated treatment antennae is used in the treatment of more superficial tumors of the head and neck and chest wall, etcetera.

The Whole Body, Regional and Locally applied systems of treatment are also used adjunctively with reduced doses of cytostatics following Culture and Sensitivity Testing (EVA). Some cases are treated concomitantly immediately after radiotherapy.

Some encouraging results have been seen in the short term, with a number of stage 4 patients long past their use by date. Long term survival curves remain to be seen.

HYPERTHERMIA AND THERMOTHERAPY OF THE PROSTATE
CLINICAL EXPERIENCE WITH PROSTCARE
Dr. David G. Spall, M.D., M.A., D.D.R.
Queensland Prostcare and Cancer Clinic; Brisbane , Australia

The Queensland Prostcare and Cancer Clinic has been using the system since February 1996 in the treatment of BPE (Benign Prostatic Enlargement) using Trans Urethral Microwave Thermotherapy (TUMT). Trans Rectal Microwave Thermotherapy (TRMT) is used in the treatment of prostatic carcinoma and abacterial prostatitis. Extra-capsular disease is treated adjunctively with regional and whole body hyperthermia.

The treatment system of choice is Prostcare by Odam Bruker, ( France ).

This paper presents a study of the techniques and clinical results on a wide range of patients. Retrospective review of patients with LUTS from varying degrees of BOO associated with BPE will be presented. Intra prostatic temperatures as high as 55 ° C have been obtained. Accurate intra prostatic temperature recordings are made possible by way of radiometric temperature measurement using Plank = s Law.

Excellent results have been obtained with subjective symptoms in 80% of patients, and good results in 15% of patients with BPE. Madsen Iverson Score is utilized as well as Qmax where possible.

Falling PSA levels are being witnessed in an increasing number of patients with Prostatic Carcinoma who have declined emasculation either surgically or by hormone blockade.

HEATING OF MALIGNANT PROSTATIC TUMORS
USING ABLATION TECHNOLOGIES’ THERMOTHERAPY SYSTEM
Sumner, K., Ph.D.,
Ablation Technologies, San Diego , USA

Ablation Technologies is a company focusing its efforts to develop a treatment for localized prostate cancer. It has patented the ThermoTherapy System™ (TTS) designed to treat patients using interstitial hyperthermia.

The TTS is comprised of 2 main components. The first component is a biocompatible metallic rod, 1mm in diameter by 14mm long, called a ThermoRod™. The second component is the treatment table or TTS, which generates energy necessary to activate the ThermoRods.

The procedure requires the patient to have an outpatient procedure to percutaneously implant 25-30 ThermoRods into the prostate guided with ultrasound imaging. The Patient then lies on the TTS that is then activated generating approximately a 50 gauss magnetic field oscillating at 50kHz centered on the prostate. ThermoRods within this type of field begin to heat up until they reach a specific temperature, where upon, they undergo a transition from metallic to non-metallic and the heating stops, this is known as the Curie point of the ThermoRod. These temperature self regulating ThermoRods placed in a uniform pattern ensure that a maximum temperature is reached within the prostate to ablate the surrounding tissue. Reoccurring cancer can be retreated by simply placing the patient in the TTS again.

Phase I and II clinical trials are currently in progress to study safety and efficacy. So far the therapy has been well tolerated with no significant side effects.

THERMORADIOTHERAPY WITH INHIBITION OF BLOOD FLOW IN TREATMENT OF ADVANCED ORAL AND STOMATOPHARYNX CANCER
Svetitsky, P.; Pustovaya, I.
Cancer Research Institute, Rostov-on-Don
Russia

Recently the incidence-rate of oral and stomatopharynx cancer has increased.

Material and Methods: 30 patients with advanced oral cancer were subdivided into two groups. The 1 st (studied) group received 2-weeks’ regionary polychemotherapy, with local super-high frequency hyperthermia and inhibition of blood flow in the tumor. Then radiotherapy was performed. Hyperthermia was performed with the set "Yachta-3", frequency 915 MHz, temperature 41-42 C. Inhibition of blood flow was performed by paratumoural administration of Phenylephrine hydrochloride (1% solution). The control group received the same treatment without inhibition of blood flow.

Results: Complete clinical response in the studied group was achieved in 4 (27%) patients, partial - in 9 (6%), the reduction of the tumor by less than 50% - in 2 (14%) patients. In the control group we received worse results: complete effect - 1 (7%) patient, partial - 7 (47%), no effect - 7 (47%) patients. After completion of treatment radical operation was performed in 12 (7%) patients of the studied group, and in 8 (53%) patients of the control group. Morphological study revealed more marked dystrophy in removed tumors in the control group.

Conclusion: Thus, the results prove that complex treatment of cancer with hyperthermia and inhibition of blood flow significantly improves immediate results.

ELECTRO-HPERTHERMIA AND ITS ADVANTAGES
Szasz, A., (Ph.D.)
Professor on Physics, Godollo University , Hungary and
OncoTherm GmbH , Germany

Electro-hyperthermia differs from other hyperthermia treatment by selectively heating the extracellular matrix (ECM) of the target tissue. Most hyperthermia treatments currently in use heat an entire region, including the cells within the target tissue. The cells, in response, produce stress-tolerance proteins (chaperones) to prevent significant damage caused by the treatment [1]. The malignant tissue is thus capable of developing resistance against heat, and can significantly reduce the effect of hyperthermia treatments [2]. Furthermore, the stress-proteins, induced by hyperthermia, can reduce the chemo-sensitivity of the cells; thus the treatment can have a negative effect. Chaperone production is located within the cell, where its precursors, the heat (stress) protein factors [HSF], are located. To avoid chaperone production, our applied effect does not penetrate directly into the cell, rather it targets the ECM. The aim is to rapture the cell membrane, as well as to affect the voltage gated ionic channels without creating high stresses inside the cell. By the time high stress levels reach the interior of the cell, the damage is irreversible, causing cell death without the production of intracellular chaperones. Based on this theory, a wide range of electro-hyperthermia methods have been used ranging from DC, through AC, to RF-capacitive coupling systems, to target a wide range of malignant tissues with great success.

[1] Soti C., Csermely P.: Molecular chaperones in the etiology and therapy of cancer, Pathology & Oncology Research, 4, 316-321, 1998

[2] Li G.C., Mivechi N.F., Weitzel G.: Heat shock proteins, thermotolerance, and their relevance to clinical hyperthermia, Int. J. Hyperthermia 11, 459-488, 1995

[3] Huot J., Roy G., Lambert H., Landry J.: Co-induction of HSP27phosphorylation and drug resistance in Chinese hamster cells, Int. J. Oncology 1, 31-36, 1992

[4] Blank M.: Coupling of ac electric fields to cellular processes, presented at ElectroMed99, April 12-14, Norfolk , Virginia

INTERSTITIAL HYPERTHERMIA FOR MALIGNANT GLIOMA IN THE BASAL GANGLIA.
Takahashi, H.; Uzuka, T.; Morita, K., Tanaka, R.
Dept. of Neurosurgery, Brain Research Institute,
Niigata University Asahimachi-dori, Niigata , Niigata , JAPAN

Background: We have already treated with RF interstitial hyperthermia for malignant brain tumors. The authors report four cases of malignant glioma in the basal ganglia that were successfully treated by RF interstitial hyperthermia with stereotactic biopsy.

Material and Method: Five patients with malignant glioma in basal ganglia treated by interstitial hyperthermia with radio chemotherapy. Gold needle-shaped applicators (RF antennas) were inserted into the tumor using stereotactic apparatus. The heating was performed 3 to 4 sessions with radiation. The rim of tumor was heated at 42-43C for 40 - 60 min.. All cases had no indication of removal in tumoral location (4 thalamus and 1 putamen). The tumoral size was 20 to 40mm in a diameter. Result: The patients complained no local pain or heat sensation and well tolerated the repeated heating. No major complication occurred except pneumonia in 1 patient. The anti-tumor effects were evaluated by CT and the treated tumors showed CR in 2, PR in 2 and ST in 1 case, respectively.

Conclusion: The RF interstitial hyperthermia seemed to be effective in treatment of inoperative brain tumors. This technique is less invasive and the tumors in aged or poor risk patients as well as deep-seated tumors can be good candidates for the application.

INTERSTITIAL HYPERTHERMIA OF ORAL CANCER
-CLINICAL STUDY OF IMPLANT HEATING SYSTEM (HIS) AND
EXPERIMENTAL STUDY USING MAGNETIC CATIONIC LIPOSOMES ((MCLs))-
Tohnai, I.; Mitsudo, K.; Matsuno, H.; Goto, H.; Hayashi, Y.; Ueda M.
Department of Maxillofacial Surgery, Nagoya University , Nagoya , Japan

We have recently developed a new system of magnetic induction hyperthermia called implant heating system (IHS) using ferromagnetic implant. IHS consists of a ferromagnetic implant induction coil and generator. The ferromagnetic implant is made of FE-Pt alloy, and has a Curie temperature of 68 C. Nineteen patients with primary cancer of the oral cavity were treated by thermochemotherapy. Thirteen patients of them underwent preoperative combination therapy with IHS and chemotherapy. While the other six patients underwent thermochemotherapy without surgery. They received two courses of chemotherapy, which included infusion of 100 mg. of cisplatin (CDDP) and 25 mg. of peplomycin (PEP) as a rule. The patients also received interstitial hyperthermia for 45 min. once a week using HIS.

Results: Thirteen patients were treated preoperatively. As a result, clinical complete response (CR) was observed in 11 patients and partial response (PR) in 2 patients. Postoperative pathological examination showed no tumor cells in specimens of 12 patients. However, a few tumor cells were observed in one patient with T3 cancer. The other 6 patients were treated by thermochemotherapy alone. As a result, CR was observed in six patients, however, recurrence was observed in one patient with cancer of the hard palate.

Conclusion: This therapy not involving surgery or irradiation is considered to contribute too improvements in QOL of oral cancer patients. However, this method has a disadvantage that many implants were inserted into the tumor in the progressive tumor. Therefore, we are developing the new interstitial hyperthermia using magnetic cationic liposomes (MCLs) as ferromagnetic body, furthermore. We will report the experimental results of this hyperthermia.

DEEP REGIONAL HYPERTHERMIA WITH THE
BSD-2000•3-D SYSTEM;
Turner, T.
BSD Medical Corp.; Salt Lake City , Utah , USA

BSD has developed a three dimensionally steered 24 dipole deep heating phased array system. The system operates with the 24 dipole phased array Sigma Eye hyperthermia applicator and other Sigma Applicators. This system has also been integrated with a MR system which is capable of providing MR imaging simultaneously with deep focused and regional heating. Although the MR project has not been fully evaluated in the clinic yet, early results are promising to provide non-invasive treatment monitoring using the MR. The newly designed 12 channel solid-state amplifier provides for 12 independent power and phase control channels to provide full 3D heating pattern control non-invasively. The demonstrated ability to steer and shape the deep heating pattern demonstrates that the energy focal zone can be electronically directed to either deep or superficial targets. The complete electronic control of the heating pattern in three dimensions provides dynamic control of the heating zone to optimize the heat delivery and reduce heating of normal tissues.

The use of the Hyperplan patient specific pretreatment planning system provides an unparalleled training and planning capability to visualize the heating action and localization. This numerical method was originally developed at Stanford University and later refined at a leading research center in Berlin . This provides an excellent tool for operational training as well.

The use of both pretreatment planning with Hyperplan and invasive and/or non-invasive electric field sensors is expected to lead to optimal phased array energy steering and optimal tumor heating. The addition of dynamic heating control in combination with the MRI system integration option (for non-invasive treatment monitoring), is expected to greatly improve deep focussed and regional hyperthermia treatment in the future.

HYPERTHERMIC TREATMENT PLANNING USING COMPUTER SIMULATION FOR MALIGNANT GLIOMA
Uzuka , T.; Takahashi , H.; Kakinuma , K.; Tanaka , R.;
Matsuda, J.* ; Kato, K.*
Department of Neurosurgery, Brain Research Institute, Niigata University ; Niigata , Japan
*Department of Engineering, Nagaoka University of Technology;
Nagaoka , Japan

We have been treating with interstitial hyperthermia using radiofrequency generator for the patients of malignant glioma. It is important to make a treatment planning based on an accurate temperature distribution prediction for hyperthermia. To make a treatment planning for clinical use, handiness and simplicity are also demanded. A new method of treatment planning for interstitial brain hyperthermia has been designed, and the clinical usefulness of the method was evaluated. Two-dimensional finite element method was used for the simulation of temperature distribution . The temperature distribution was calculated by the bioheat transfer equation. The estimated area above 42 C could be adjusted to the contrast enhanced lesion on the CT images. Actual temperature was measured at one point on 42.0 C of calculated temperature, where was considered as a key point of thermometry because of the anatomical features of the tumor and the surroundings. Five cases with malignant gliomas were planned the treatment using this method perspectively, and heated with 13.56MHz radiofrequency generator, measuring the actual temperature. As the result, optimal position and number of the needle type applicator were decided without difficulty and complexity in all cases. The temperatures at the thermometry point became 41.5 - 42.6 C, and steady heating were done for over 20 min. The mean rate of the obtained necrosis was 74.8%. In three cases, over 80% necrosis was recognized and the shape of the necrosis in these cases well adjusted to the estimated areas above 42.0 C. All cases were heated safely under appropriate technical conditions with adequate thermometry. These results indicate that the newly developed treatment planning is clinically useful for interstitial hyperthermia of malignant glioma.

EXTERNAL THERMORADIOTHERAPY TREATMENT FOR PROSTATE CANCER. AN UPDATE
Wolfstein, R., M. D.; Bicher, H., M. D.;
Keen, T., M. N.
Valley Cancer Institute, Los Angeles , CA , U.S.A

From the period since 1992 until 1998, seventeen patients with primary prostate cancer were treated at the Valley Cancer Institute. This group was treated with external beam radiation therapy and local hyperthermia.

Eleven of them had disease in a comparably early stage, with local and/or regional involvement but no disseminated metastatic disease. In this group of patients we experienced a complete response (CR) rate of 100%. There was no local recurrence or metastatic dissemination. All these patients experienced a decrease in PSA results, disappearance or significant improvement of local symptoms and preservation or improvement of sexual function.

Another group of five patients presented with disease in advanced stage. In this group we experienced local response rate: 80% complete response (CR) and 20% partial response (PR). However all these patients presented with or developed later distant metastatic disease. A decrease in the PSA was observed in 40% of these patients, and local symptoms improved significantly or disappeared in all cases. However, this entire group has expired.

During the course of therapy patients experienced no major side-effects, except minor symptoms of bowel irritation and some degree of skin reaction in the perineal region.

This study confirms the value of hyperthermia in conjunction with radiation therapy to control locally advanced prostate cancer, especially in its early stages.

Thermoradiotherapy proves to be useful in later stages to improve local symptomatology, especially pain and urinary retention, without significant side-effects.

INTRACAVITARY HYPERTHERMIA COMBINED WITH
EXTERNAL RADIATION IN THE TREATMENT OF UTERINE CERVIX CANCER
Li Ruiying, Cui Xiao-Li, Wang Ping
Tainjin Medical University Cancer Hospital ; Tianjin China

Purpose: To determine the effect and complication of Thermoradiotherapy in the treatment of advanced cervical cancer.

Methods: From 1984 to 1996, 160 patients with advanced cervical cancer received combination intracavitary hyperthermia with external radiation. Heat was introduced by the 915 MHg equipment with intracavitary applicator of 160 cases included stage II 120, Stage III 37, stump cancer 3, squamous cell carcinoma 154, adenocarcinoma 4, others 2. Heat was given twice a week, 40 minutes per time with the total of 8-14 sessions, radiation was performed by Co or 8 MV X-ray with anterior posterior opposed field or box field. The total doses were 60-70 through shrinking field technique.

Results: The median follow-up time was 156 months (range 29 to 174 months) the 5-year survival rates were 63% (stage II), 60% (stage III) respectively, the 10-year survival rates were 42. 1%, 37% respectively, no patients occurred severe complication.

Conclusion: It is suggested that thermo-radiotherapy may play an important role in the treatment of uterine cervix cancer.

RADIOTHERAPY COMBINED LOCAL HYPERTHERMIA FOR TREATMENT OF ADVANCED OR RECURRENT BREAST CANCER
Cui Xiao-Li, Li Ruiying
Tianjin Medical University , Cancer Hospital ;
Tianjin , China .

Purpose: To evaluate the effect of radiotherapy combined local hyperthermia in the treatment of advanced or recurrent breast cancer. Methods: From January 1980 too August 1994, 100 patients with advanced or locally recurrent breast cancer were treated with radiotherapy combined local hyperthermia the age of patients range from 30-78 years with a median of 54 years. In 26 patients with primary breast cancer, the lesion were classified as clinical stage III, the other 74 patients had recurrent breast cancer following surgery and irradiation (40-65cGy,) the size of recurrent lesions on the chest wall. Altogether there were 138 lesion treated. Average size of tumors treated with combined therapy was 39.2cm. in area and irradiation alone was 14.2cm. Hyperthermia was given by using microwave of 2450 MHz twice a week. 30 minutes after irradiation intratumoral temperature was maintained at 41-44 C. for 40 minutes. An average of 11.6 sessions of heat was given. Radiation therapy was delivered by conventional fractionation 2-2.5Gy/dayx4-5 weeks to reach a total dose of 40-80Gy.

RESULTS:

Response %

Group No. of Size Dose CR PR NR 5 year survival

Lesion (cm 2) (Gy)

RT+HT 98 39.2 48 60.2 34.4 5.4 31%

RT 40 14.2 47 31.8 56.0 12.2 29%

Table I. Response of 138 lesions to irradiation V.S. irradiation plus hyperthermia

Although the CR rate in RT=HT group is much lighter than RT alone group, the 5-year survival is same. All patients died from systemic involvement.

Conclusion: Local hyperthermia combined with radiation therapy is a well accepted modality for treatment of advanced or recurrent breast cancer.

THE ANTI-TUMOR EFFECT OF TWEEN-80 IN COMBINATION WITH HYPERTHERMIA IN TUMOR-BEARING MICE
Yao-qin Yang, Hu-chuan Yang, Hui-hong Tao, Wen-ji Piao
Tumor Cytology Research Unit, Medical college, Shanghai Tiedao University ; China

Abstract: Objective: Studies on the influence of Tween-80, a membrane-active agent, combined with hyperthermia at 41 E C on B16 Melanoma cell and tumor-bearing mice. Methods: B16 melanoma cells were inoculated into the BALB/C mice to establish melanoma-bearing models. The expression and distribution of hsp70, c-fos and ubiquitin in B16 cells were studied by immunocytochemistry. The changes of growth curves, ultrastructure, SDH and 5-Npase activity of melanoma and peritoneal organs of tumor-bearing mice were observed after treatments. The serum TNF and sialic acid (SA), the survivals time and mortality of tumor-bearing mice were assayed. The number of pulmonary metastatic tumor foci from blood flow was also detected. Results: The results showed that B16 cells expressed all hsp70, c-fos and ubiquitin protein at 37 E C in different level. They mainly located in cytoplasm, except for c-fos. Hyperthermia could increase expression of hsp70, which was significantly inhibited by combined action. But c-fos and ubiquitin expression obviously increased by Combined action. Tween-80 combined with hyperthermia at 41 E C could survive the tumor-bearing mice and decrease the number of pulmonary metastatic tumor foci and dramatically suppress the growth of the melanoma in the feet of mice but no significant effects were observed by treatment with Tween-80 or hyperthermia at 41 E C alone. The activities of TNF and the level of SA of the melanoma-bearing mice kept at higher levels than those of normal BALB/C mice did. Tween-80 combined with heating 41C significantly decreased the activities of TNF and increased the level of sSA that decreased 10 weeks later with the tumor regression. Morphologically, the feature of the cell death coincided with the descriptions of the mode of apoptosis and suggested that this process could relate to trigger programmed cell death. On the structure and activities of SDH and 5-NPase in the normal organs, the effects of combining action were slight and temporary. Conclusion: These results demonstrate that Tween-80 may make hyperthermia exert effective anti-tumor effect below the critical temperature and increase the safety of hyperthermia in treatment. It could be one of the most ideal synergist with hyperthermia.

STUDY OF 1-3 YEAR SURVIVAL RATE OF MALIGNANT CEREBROMA
TREATED BY INTRAOPERATIVE HYPERTHERMIA AND Ir BRACHYTHERAPY
Liu Ling Yi Tianjin 2 nd. Central Hospital ; Tianjin , P.R. China
Wang Zhao Ming, Tianjin 2 nd. Central Hospital ; Tianjin ; P.R. China

From July 1992-Dec. 1995, 30 patients suffering from malignant cerebroma proved by pathological examination were treated as following:

A total or partial excision of cerebroma was performed

The tumor sites were accepted the microwave hyperthermia (2450MHz) the shape of the applicator is globular with diameter from 3-5cm. The treating temperature is 44 E C for 30 min.

After that, the tumor sites were placed 1-3 brachytherapy tubes in parallel, the patients took the brachytherapy (192 Ir) in 3-7 days after the operation, the total dose:1100-5000cGy.

All patient were followed in 41 months

The average survival period of malignant cerebroma taken operative treatment solitarily is 17 weeks. This group compared with the group taken operation combined intraoperative hyperthermia, the average 1-3 year survival rate is:

Operation + Operation +

Intraoperative hyperthermia intraoperative hyperthermia + 192 Ir Brachytherapy

1 year 12/30 (40%) 16/30 (53.3%)

2 year 4/30 (13.3%) 8/30 (26.7%)

3 year 3/30 (10%) 6/30 (20%)

The 1-3 year average survival rate in this group is higher than that of the group which was taken the operative treatment combined intraoperative hyperthermia.

CLINICAL TRIAL OF THE FEASIBILITY, SAFETY, AND EFFICACY OF FOCAL MICROWAVE HYPERTHERMIC TREATMENT OF BREAST CANCER
Vargas, H.; Block, J.; Gardner, R.; Vogel, C.; Fenn, A.
Harbor UCLA Medical Center; Torrance, California, USA
The Center for Breast Care at Columbia Hospital; West Palm Beach, Florida, USA
Lincoln Laboratories, Massachusetts Institute of Technology; Boston, Massachusetts, USA

BACKGROUND: Clinical trials have not shown a clear benefit of hyperthermia in addition to radiation therapy alone. The negative results may be the result of equipment that was capable of heating only very small superficial tumors with a diameter of less than 3 cm. Deep-seated tumors could not be heated completely by the hyperthermia equipment. However, subset analysis of the response of tumors with diameters less than 3 cm reveal an improvement in tumor response from 39 percent (radiation therapy alone) to 52 percent (radiation therapy plus hyperthermia).

HYPOTHESIS : A possible solution to the deep delivery of heat for the treatment of cancer is an adaptive microwave phased array technology, which has the unique advantage of focusing energy. Due to its accessibility, breast cancer may be best suited for this therapy

OBJECTIVES: The study aims are:

To evaluate the technical performance of the microwave treatment system and the clinical operations.

To determine the safety of focused microwave heating of the breast.

To establish the impact of the hyperthermia with focused microwaves in normal breast and in breast cancer tissues.

To observe changes induced by hyperthermic treatment with MRI.

DESIGN: Ten patients will undergo focused microwave hyperthermic treatment of deep-seated breast cancers less than 3 cm in diameter. Patients will be followed for a period of 5 to 21 days until the performance of mastectomy. The patient will be followed for evidence of toxicity and for response. Tumor response will be measured by final pathologic tumor staging and correlation with the original clinico-radiologic-pathologic assessment.

For More Information Contact:

International Clinical Hyperthermia Society
1502 East Country Line Road South
Tel: 317-887-7651
FAX: 317-887-7650
Internet: info@hyperthermia-ichs.org

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