Summary of abstracts
22nd International Clinical Hyperthermia Society

THERMORADIOTHERAPY FRACTIONATION IN THE CLINICAL
TREATMENT OF MALIGNANT TUMORS
Bicher, H., M. D.
Valley Cancer Institute, Los Angeles, CA, U.S.A

Hyperthermia has been proven to increase the response of malignant tumors to radiation therapy in both experimental animal tumors and the clinical treatment of human cancer. Based on our multi-year experience, first in re-treatment of previously radiated fields that necessitated the use of low dose radiation fractions as adjunct to the heat treatments, and then progressively applying the encouraging results obtained to areas treated "de novo" and eventually to situations allowing a potentially curative intent, treatment protocols have been devised and tested that yield positive preliminary data showing superior tumor response rates and less side effects when compared with historical controls at our Institute.

The hyperthermia part of the protocol extends the number of heat treatments to correspond to the number of radiation-fractions, as each hyperthermia treatment proceeds or follows each radiation treatment in close time proximity. The number of hyperthermia treatments therefore varies from 25-50 per course for each treated field.

The radiation protocol consists of progressively decreasing daily doses of radiation therapy combined with the daily hyperthermia treatments. Typically the treatment is started at a daily dose of 180cGy gradually reduced to 100cGy protracting a typical radiation therapy treatment course from 5000cGy in five weeks to 5000cGy given in over eight weeks; or 7000cGy in seven weeks to 7000cGy in 14 weeks. According to the ELLIS TDF formula, this results in a 15% or 25% reduction of the effective radiation dose. The total dose is of course adapted to the clinical situation.

The following Conclusions are drawn:

CONCLUSIONS
Protracted Hyperfractionation

Decreases the radiation dose by 15% and 24%.
Decreases the side effects of XRT (no diarrhea, fistula or pneumonitis in PH cases)
Allows for more combined XRT-Hyperthermia treatments
Increases the effectiveness of the combined treatment in superficial and deep tumors.
Question: What is the lowest radiation dose needed to potentiate Hyperthermia?

1

THERMORADIOTHERAPY IN BREAST CANCER – THE
TREATMENT OF LOCALIZED INFLAMMATORY
RECURRENCE
Bicher, H., M. D.; Wolfstein, R., M. D.;
Keen, T., M. N.; Carter, S., Ph. D.
Valley Cancer Institute, Los Angeles, CA, U.S.A

Thermoradiotherapy is well established as a primary or adjunct treatment of mammary adenocarcinoma. Results in our series since 1984, encompassing 142 treated patients show a 90% response rate of which 72% are complete responses. However, when local treatment is done in the face of disseminated disease, the response rate is markedly reduced. Response rate increases with the number of hyperthermia treatments.

Localized inflammatory breast cancer, usually extending from the affected breast or mastectomy site to the chest wall is a rapidly lymphatic spreading form for cancer, usually resistant to radiation or chemotherapy, and prone to rapid dissemination.

This presentation reports on a phase 1 clinical trial involving 71 fields in 16 patients. Each field received 2000-4000cGy of external beam bolused radiation combined with 25 or more hyperthermia treatments given within one hour of the radiation.

Response rate was gratifying. 90% of the fields responded to the combined treatment, with complete disappearance of the inflammatory process in 81% of the treated areas. There was only one recurrence in the areas of complete response while areas that responded partially showed regrowth within 3 months of treatment. Side effects were minimal, in the form of 6 first degree superficial burns. There was no correlation between the response rate and the radiation dose.

These preliminary results show that thermoradiotherapy should be considered as a treatment modality for inflammatory breast cancer.

2

HYPERTHERMIA OF TUMORS AT THE 0.88 MHz
Brusentsov, N. A. ¹, Jurchenko, N. Y.¹, Sergeev, A. V.¹,
Shumakov, L. I. ²
1.Russian Cancer Research Center RAMS; Russia, Moscow
2. Russian Radiotechnical Research Institute; Russia, Moscow .

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SOME MECHANISMS OF ANTICANCER AND MODIFYING ACTIVITIES OF "INORGANIC" COBALT(III) COMPLEXES (AC-series)
Bubnovskaya L.¹, Levitin I.², , Sigan A.², Ganusevich I.¹
Michajlenko V.¹, Kovelskaya A.¹, Nechiporuk-Zlyj V.^1
1Inst.exp.Pathol.Oncol.Radiobiol.; Kiev, Ukraine
²Inst.Organoelement Compounds; Moscow , Russia

Objectives: to study the mechanisms of biological activities of "inorganic" cobalt(III) complexes with different biogenic ligands.
Materials&Methods: some "inorganic" cobalt(III) complexes that are containing no metal-carbon bond, were tested in vivo. Here they are exemplified by AC-30 complex. Transplanted rat tumor (Guerin carcinoma) was used in this study. Complex was given i.p. or i.v. Local hyperthermia (LHT) (1 h, 43 or 41⁰C) was performed by microwave unit. The levels of glutathione (GSH) and malonyl dialdehyde (MDA), glutathione S-transferase (GST) activity in tumor and normal tissues and some indices of kidney and liver functions were determined by biochemical methods. Energy status in tumor and muscle was determined by ³¹P NMR spectroscopy.

Results: MDA concentration was increased by a factor of 3.5 in tumor to the 60^th min after AC-30 injection, in liver and kidney - 1.5 and 2, respectively. GSH content was decreased by a factor of 2 in tumor at the same time, in liver and kidney - by 10% and by a factor of 3, respectively. GST activity was decreased by a factor of 2 in tumor, in liver and kidney - by 10 and 20%, respectively. Decreased both MDA content and GST activity in tumor were kept unchanged within 24 h. All indices in normal tissues were reached the pretreatment values to the 24 h. AC-30 caused an drastic decrease in high-energy phosphates in tumor to the 2^nd h after injection. Tumor bioenergetic status has been reached the pretreatment level to the 24^th h. Kidney and liver functions were not significant disturbed due to AC-30 within 14 days.

Conclusion: it may be supposed that "inorganic" cobalt complexes exhibit anticancer and modifying effects by selective formation of free radicals in tumor (due to its hypoxia) which attack biomolecules and structures of cancer cells. Their influence on matrix proteinases can not be excluded.

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SOME CHEMICAL CONSIDERATIONS ON THE TUMOR GENESIS STARTING
FROM ANALYTICAL DATA
*Campanella, L.; Giudiceandrea, F.; Pigliucci G.M.
*University of Rome LA SAPIENZA, Chemistry Department – Italy
University of RomeTOR VERGATA, Department of Surgery - Italy

The analytical determination performed in the environmental compartments (water, air, soil) show that some common polluttants are present at increasing concentrations. This is particularly true in case of heavy metals (Cd and Pb over all), hydrocarbons (expecially BTX), pesticides (meaningly organophosphoric and carbammic ones). Correspondingly always more numerous cases of tumours of liver and kidney are recorded so that possible correlations between the two phenomena can be investigated. The increasing concentration of organic polluttants in the environment can bring to their progressive accumulation in the target organs with formation of adducts to DNA and following cellular degeneration. The organism defends itself with metabolic and enzymatic activities finalised to consume these accumulated species. A study was performed on several cases (50<n<100) of cancerous and healthy kidneys and livers. So in the case of benzene metabolic capacity of kidney cancerous and healthy tissues due to the dioxigenase activity was measured. Higher values in the case of cancerous than healthy tissues were recorded so a defence mechanism activation being evidenced. Unfortunately the metabolic reaction produces metabolytes as muconaldheyde more toxic that benzene itself. To contrast this damage the introduction of a competitive agent of benzene toward dioxigenase, obviously characterised by non toxic or easily excreted by and final products, can be hypotized. This action can be probably enhanced by operating under heat, according to the parallel research performed by Roman University.

The conclusions are:

in cancerous organs cancerogenic environmental polluttants are accumulated.

to eliminate these accumulations it is necessary to adopt two different actions: firstly to add radical scavenger able to lower radicalic concentration and so their inhibiting action on the enzymes; secondly to prevalently enrich the oxidative enzymatic equipment of the singles especially if exposed to cancer risk.

REFERENCES

L. Campanella, G. Favero, M. Tomassetti
A modified amperometric electrode for the determination of free radicals.
Sensors and Actuators B 44; 559-565, 1997
Campanella L., Favero G., Mastrofini D., Tomassetti M.
Further developments in toxicity cell biosensors
Sensors and Actuators B 44; 279-285, 1997
Campanella L., Favero G., Tomassetti M.
A biosensor for determination of free radicals
In R. Puers (Ed.), Proceedings of Eurosensors X, The 10^th European Conference on solid-state trasnsducers, vol.3, Leuven 917-918, 1996
Campanella L., Favero G., Persi L.,Tomassetti M.
A superoxide dismutase biosensor to evidence the anti free-radical properties of healty and cancerous kidney tissues
SIB-BIB, Como, 28-30 april 1990
Campanella L., Favero G., Persi L.,Tomassetti M.
New sensors and biosensors for superoxide radical to evidence molecules of biomedical and pharmaceutical interest having scavengers properties.
8^th International Meeting on recent developments in pharmaceutical analysis, Rome 29 june-3 July 1999

6

HOMOGENEITY OPTIMIZATION OF TEMPERATURES AND DRUGS DURING PERITONEAL HYPERTHERMIC-ANTIBLATIC FOR PERITONEAL CARCINOMATOSIS

De Simone, M.; Nano, M.; Barone, R.; Izzo, G.; Cistaro, A; .Bacino, A.; Mattalia, P.; Aimone, M.; Cassolino, P.; .Camerano, R.; Villata, E; et Dei Poli M.

Università di Torino – Azienda Ospedaliera S.Giovanni; Torino, Italy

The peritoneal hyperthermic-antiblastic perfusion (HAPP) in partnership to the surgical cytoreduction seems one of the few weapons to disposition in the therapy of the peritoneal carcinomatosis. The presuppositions of such treatment are : 1) the presence of a peritoneal-plasmatic barrier, that allows to infuse great drugs concentration without systemic toxic effects ; 2) the synergic antineoplastic effect of e hyperthermia, with some drugs.

Varied groups of surgeons of the world have adopted two different types of HAPP : The "Closed Abdomen" one and the "Open Abdomen"one . The perfusion in closed abdomen is the fastest: at the end of the surgical cytoreduction, it foresees the closing of patient’s abdomen and than the perfusion of abdominal cavity is carried out through drains preventively set. The defect of this methodic is the dishomogeneity of drugs and temperature distribution. This is confirmed by no complete metilen blue diffusion introduced in the perfusion circuit (Sugarbaker). Aware of this limits many Authors have proposed some expedient : to shake the patient, to vary the inclination of the operating bed, to reverse the flow of the perfusion, to use very hot inflow temperatures (48°- 52°) (Gilly). Japanese authors have still proposed hot temperatures and fast flows (3 liters/min), which however are difficult to maintain in closed abdomen. Finally, a French author has proposed the use of 4 pumps and two heat exchanger, with low success.

To create an abdominal cavity, the perfusion in open abdomen foresees to suspend the skin of the incision to an "self retaining" retractor anchored on the operating bed and whose oval is set 10cms above the patient. The perfusion tubes are connected to a propulsion system made of two pumps, one for suction and one for feeding. These pumps are linked trough a reservoir that act as level regulator. During the whole perfusion the surgeon’s hand mix the solution in order to homogenize temperature and drugs.

The defect of this technique are the high thermodispersion and the risk of operating room contamination with drug , in case of leakage from abdominal cavity.

Materials and methods : due to the above mentioned reasons , in the last 27 patients we have tried to modify the "open abdomen" technique and to optimize the suction and feeding system. The partially closed abdominal cavity has been suspended to an self-reteining retractor , and we have called this method "partially closed" , leaving nevertheless an opening on the top which allow the introduction of the hand of the operator. This technique has allowed a lower thermodispersion , almost no contamination , better "hollow effect" , and a faster temperature uniformity. We have also worked to define the number and

7

the dimensions of the hole in the inflow and outflow tubes. Actually we get quickly homogeneous intraperitoneal temperature using a system with 3 outflow tubes of 24F diameter ( under right and left diaphragm , pelvis) and 2 Y inflow tubes of 18F ( sovra e sotto mesocolico) . The 2 inflow tubes are the results of various experimental test to obtain Y branches with different lenght and holing in order to get the best diffusion of the solution.

Results and conclusions : starting from the partially closed perfusion use , the problem related to the contamination of the operating room are reduced , maintaining a good abdominal cavity edges perfusion and high flow (1,5 lt/min). In the last 12 cases with Y system and different length and holing , we have reached optimal and homogeneous temperature (42°C in the peritoneum) in a very short time and inflow temperature that are not over 44,5°C.

8

CYTOREDUCTION AND HYPERTHERMIC ANTIBLASTIC PERITONEAL PERFUSION IN RECURRENT OVARIANT CANCER AFTER 1^ST LINE OF CHEMOTHERAPY

M.De Simone, R.Barone, M.Nano, A.Bacino, E.Villata, M. Vaj , C.Franco, P. Cassolino, R.Camerano, A.Cistaro

Università di Torino – Azienda Ospedaliera S.Giovanni; Torino, Italy

The survival of patients with advanced ovarian carcinoma is 20% to 5 years. The middle survival at the moment of the recurrence after the first line of chemotheraphy ranged from 16 to 20 months. After surgical remove of a ovarian cancer at II or III stage, the recurrence is to load of peritoneum in 90% of cases. Initial studies regards the cytoreduction+chemo-hyperthermya in multi-recurrences ovarian carcinoma have given encouraging results, so that they stuffed us to propose a protocol of treatment in order to appraise the impact of the methodic on patients with first neoplastic recurrence intraperitoneal after chemotherapy. The protocol foresees also the execution of the lymphadenectomy, where it had not been already performed. A sistemic chemotherapy of consolidation within 5 weeks after intervention is provided.

Materials and methods : 5 patients with intraperitoneal recurrence, appearance not before 3 months from the end of chemotherapy effected for primitive ovarian cancer, have been enlisted. They have been submitted to laparotomy with surgical cytoreduction, up to reach max tumoral dimensions, for every knot, of 1cm and to lymphadenectomy aorto-cavale and iliac-hypogastric. The hyperthermic-antiblastic intraperitoneal perfusion has been performed with 25 mg/l/mq of Cisplatino, in 4 liters solution, at temperature of 42°C on peritoneum, for 90mins. In all patiens the peritoneum illness was not particularly advanced (Peritoneal Cancer Index ranged from 1 to 10). The cytoreduction has been complete in all cases. In three cases the lymphadenectomy has been performed. In a case had been already done during the first surgical interventionOnly one patient has resulted N+.

Results and conclusions : Nobody of the treated patiens have had post-operating complications, neither local or systemic toxicity from Cisplatino except one case which suffered for a very long post-operative ileum. The therapeutic meaning of the lymphadenectomy is still uncertain and the literature data scarce still. Any complications due to the association lymphadenectomy+peritoneal perfusion, occured in our cases. In the other hand, once performed the pelvic pertonectomy, the lymphadenectomy aorto-cava-iliac-hypogastric is easy enough and it prolongs surgical time of c.ca 90-120 mins.

9

USE OF ^99mTc MICROCOLLOID IN THE BLOOD LEAKAGE MONITORING DURING HYPERTHERMIC ISOLATED LIMB PERFUSION

M.De Simone, M.Baccega, P.Cesana, G.Izzo, M.Aimone Secat, R.Barone, A.Cistaro
Università di Torino – Azienda Ospedaliera S.Giovanni Torino, Italy

In order to avoid complications after isolated Hyperthermic limb perfusion several measurements methods of blood leakage are currently employed. Such methods may be affected by various problems due to stability of chemical binding of the compound in heparinate blood, low sensitivity and radiation protection normative.

99mTc- microcolloid (99mTcMC) was tested as a leakage indicator on a group of 32 patients undergone isolation perfusion for the treatment of malignant melanoma. 99mTc was preferred to Iodine to minimize radiation protection problems such as contamination of surgery tools, operating room and management of the patient.

99mTcMC was chosen for its high compound stability in the extracorporeal circulation

Our technique was already presented in ICHS Congress in 1997. Now we want to report results about method.

Pharmacokinetic studies confirm the high sensibility of the method. Pharmacological leakage is indeed less than 99Tc leakage and this means that our method is able to detect in real time minimal leakages. We considered the first 8 cases necessary for learning the method.

In the last 24 Isolated limb perfusions we change flow and the position of cannulae to achieve very low leakage rates. Only three times , for technical reasons, we couldnt have a leakage detected by Tc99 inferior to 15%.

As clinical confirmation we have had in the last 24 cases a very high rate of Histological Complete Response : 6 complete response in 8 Soft Tissue Sarcomas, and 8 in 16 in transit metastasis from melanoma. All the other 10 patients had histological responses of more than 70%.

In conclusion we believe that leakage measurement by Tc99 in Isolated Limb Perfusion is very effective, and can allow better clinical results in advanced neoplasms of extremities.

10

HYPERTHERMIA AND COLONY STIMULATING FACTORS.
Goliaei, B; Jalal, R.; Khoei, S.; Minuchehr, Z.; Rajabi, H.Siamaki, K.; Soheili, Z.
The laboratory of Biophysics and Molecular Biology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, I.R.Iran.

Colony-stimulating factors (CSF) are hematopoietic growth factors which regulate differentiation and maturation of blood stem cells in normal physiological conditions. We have studied the effect of hyperthermia on the production of Granulocyte-Macrophage CSF (GM-CSF) by the lung tissue under various conditions. When mice lung tissue was minced into small pieces and heated in-vitro, there was a reduction in the production of GM-CSF in the heating range of 40-46 ^oC as judged by the colony formation assay in the soft agar tissue. The reduction was dose dependent. Under similar heat treatment, the total protein synthesis by the lung tissue showed a different pattern indicating a specific effect of hyperthermia on GM-CSF production as compared to most other proteins synthesized by the lung. Also, the activation energy of the two processes was found to be different. When the RNA from the heat-treated lung tissue was extracted and studied with slot blot analysis using a GM-CSF probe, it was observed that there was a specific reduction in GM-CSF gene expression in heat-treated lung tissue. In another group of experiments the chest area of rats was heat-treated in-vivo for one hr using a radio frequency heating device in the range of 38-41 ^oC. The animals were divided in two groups. The first group was sacrificed immediately after heat treatment and their lung was removed and assayed for the production GM-CSF. The second group was allowed to survive for various times after heat treatment to allow recovery from heat damage. The result showed that hyperthermia inhibited the production of GM-CSF within a few hrs after heat treatment, however; the animals could recover from this damage if they were given enough time after hyperthermic treatment. In conclusion, there are evidences that hyperthermia reduces the production of GM-CSF by the lung in a dose-dependent manner.

11

DEEP HYPERTHERMIA WITH SHORT WAVES OF PATIENTS WITH ADVANCED STAGE LUNG CANCER

Hager, E. D.; Krautgartner, I., H.; Popa, C.; Höhmann, D.; Dziambor, H.

BioMed-Klinik Betriebs GmbH
Bad Bergzabern, Germany

Objective: Lung cancer is the leading cause of death from malignant disease in Western countries both in males and females. With respect to prognosis and therapy lung cancer is separated in small-cell (SCLC) and non-small-cell (NSCLC) subtypes. Approximately 75-80% of lung carcinomas are of NSCLC subtype, which includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Two thirds of all pts. with lung carcinoma will be diagnosed only at advanced stages of disease and are inoperable at the time of presentation because of either locally advanced disease or macroscopic dissemination. Surgical resection is the appropriate treatment of stage I, II and IIIa NSCLC, but at least 50% of these pts. will develop local relapse and/or distant metastases. The prognosis of pts. with advanced lung cancer is still poor, with a median survival not exceeding 8 months in large prospective studies of treated pts.. Long-term survivors (i.e., those who live more than 3 years) represent less than 5% of pts.. Polychemotherapy regimens reveal response rates (RR) of 25% to 40% among previously untreated pts. with NSCLC (<5% CR), and 60% to 90% among pts. with SCLC. The median time to progression is 3.7 to 4.2 months. New drugs are gemcitabine, vinorelbine, taxanes, irinotecan, and topotecan, which all have shown RR of 15% to 25% in previously untreated pts. Relapses indicate a very poor prognosis, depending from duration of relapse free time, because of high drug resistancy. Stage of disease, performance status and weight loss are definite predictors, including laboratory tests as lactate dehydrogenase and albumin. The poor outcome of chemo- and radiotherapy, especially after tumor relapse, and the treatment related toxicities are reasons for the search for new treatment modalities.

Patients and Methods: From 02/94 to 11/98 63 pts. with histological proven SCLC (n=10) and NSCLC (n=53) at far advanced stage of lung cancer have been treated with loco-regional deep hyperthermia (DHT) induced by radiofrequencies of 13.56 MHz (capacitive coupling). At onset of DHT all pts. were inoperable, refractory or at stage of relapse after prior surgery (30%), combination chemotherapy (46%), and radiotherapy (46%). Most of the pts. were at far advanced stage of disease (WHO/ECOG performance status 2: 36%, 3: 29%, and 4: 11%). 86% of the pts. presented with restrictive disorder of pulmonary ventilation. An essential exclusion criterion was concommitant chemo- or radiotherapy. DHT treatment was started after local or distant progression of disease after primary conventional therapies (surgery, RTx, CHTx). The median time between first diagnosis of inoperabel cancer or relapse (local and distant progression) and beginning of DHT was 3.9 months. Only 2 pts. were treated with palliative CHTx 8.4 and 28.5 months after onset of DHT due to systemic disease (e.g. pain).

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Statistics: Prospective open single arm study with intention to treat analysis.

Results: The median overall survival time (MST) of all pts. was 14.0 months from 1st diagnosis of cancer. From relapse after surgery or 1st diagnosis of inoperable cancer the MST was 10.3 months. The MST from beginning of DHT was 4.7 months, with a median time interval between progress after conventional therapy to DHT of 3.2 months. The MST from progression after conventional therapy (surgery, CHTx, and RTx) was 9.5 months. The 1- and 2-year survival rates from progression of disease were 37% and 18%, respectively. DHT related toxicity was not observed.

13

CLINICAL AND RESEARCH ASPECTS OF HYPERTHERMIA IN INDIA

Dr. Nagraj G. Huilgol and Dr. B. B. Singh

Indian Association of Hyperthermic Oncology and Medicine
Division of Radiation Oncology
Nanavati Hospital & Medical Research Centre,
Mumbai, India

The clinical use of hyperthermia in ancient system of traditional medicine (Ayurveda) in India has been known since 3000 B. C. It forms a part of an elaborate clinical protocol called "panchakarma" which is used for curative as well as preventive purposes. The protocol consists of vie purificatory steps following whole body or local hyperthermia.In recent times it has become extremely popular and forms a special subject of medical education in Ayurvedic colleges. There are three major aspect of this protocol which arouse great scientific curiosity; firstly, the fatty diet before hyperthermic exposures implicates the role of cellular membrane. Secondly, two hyperhermic exposures are always separated by ten to fifteen days to account for thermotolerance. Thirdly, hyperthermia is a prerequisite to all the steps in the protocol, the reasons for which are yet to be ascertained. Recent investigations on dietary facts on the hyperthermic response of transplanted solid tumours have indicated that high fat diet inhibitis tumour growth as well as development of thermotolerance. Mild whole body hyperthermia has been demonstrated to enhance immunological competence in animals. Implication of these observations will be discussed.

14

SECOND GENERATION ULTRASOUND ARRAYS FOR

THERMAL THERAPY IN BREAST CANCER

Johnston, R., Ph. D.; Blight, D.; Kouzmanoff, J., MSEE

Labthermics Technologies, Inc.

Champaign, Illinois, USA

There are distinct advantages in using ultrasound energy to heat breast tissues. As can be seen on diagnostic ultrasound scans of the breast, ultrasound energy is preferentially absorbed by tumor tissue components and to a lesser extent by normal tissues. This is due in part to higher collagen and protein content in tumors. In contrast, microwave energy produces higher temperatures in high resistance tissue, such as fat, and less heating in more electrically conductive tissues, including tumor. An additional advantage of ultrasound is a selectable depth-dose" of the heating beam. By changing frequency of the ultrasound energy, we can chose a heating profile that matches depth and thickness of the tumor.

A new ultrasound therapy system has been built that maximizes the therapeutic benefits of ultrasound. The system uses 16 wedge shaped transducer elements to match variable geometries of breasts and tumor locations. These elements can be driven at multiple simultaneous ultrasound frequencies to yield a truly three-dimensional heating beam. Ultrasound energy is directed tangentially to the chest wall in order to minimize heating of ribs or intercostal muscles.

In use, the patient lies on her side with the breast over a water-filled pillow on top of the treatment array. An attached ultrasound diagnostic scanner images the breast from above. A computer stores the scans and builds a three-dimensional image of the treatment area, tumor locations, and temperature sensor locations. This information is given to the treatment-planning program. The therapy array is then electronically customized for the treatment plan. Additional diagnostic ultrasound scans can be taken during therapy to insure correct registration of patient position.

The system is presently in clinical animal trials at the University of Illinois. Applications to the FDA for human use will be made soon. The system has been designed to function as a stand-alone therapy unit or as configurable modules for the present SONOTHERM Ultrasound Hyperthermia System.

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COMBINED MODALITY LOW DOSE CHEMOTHERAPY AND THERMORADIOTHERAPY:

A NOVEL TREATMENT APPROACH FOR LOCALLY ADVANCED UNRESECTABLE PANCREATIC CARCINOMA

Kawana, A.,M. D.; Quasabian, L., M. D.; Bicher, H., M. D.

Surgery Hematology Oncology Medical Association;
Los Angeles, California, USA
Valley Cancer institute; Los Angeles, California, USA

Abstract: Case Study

Despite recent advances in the treatment and diagnosis of locoregional pancreatic carcinoma only 10 too 15% of cases are amenable to resection. Unresectable tumors are often complicated by pain, anorexia, weight loss and fatigue. This case study explores the use of palliative combined thermoradiotherapy with low dose 5-fluorouracil. The patient is a 75 year old male with a two month history of severe abdominal pain and bloating. CT scan of the abdomen revealed a 4.5x3.6cm. mass in the pancreas encasing the splenic artery. CT guided needle aspiration revealed adenocarcinoma. Initial CEA was 3.7ng.ml and CA 19-9 was 108 u/ml with a pain scale of 10 of 10 despite narcotic analgesics. The patient began treatment with hyperthermia and low dose radiation to the pancreas and leucovorin 100mg. IVP weekly with 5-fluorouracil 1500mg. by continuous IV infusion (800mg/m2) over seven days. The patient experienced almost immediate pain reduction to 5 of 10 after the first day of hyperthermia. The patient’s tumor markers inexplicably rose two weeks after the initiation of treatment to CA 19-9 of 161u/ml and a CEA of 4.29 ng/ml. One month after ignition of therapy the patient was pain free off narcotics and had no symptoms of anorexia or fatigue. After six months of therapy the patients CA 19-9 had decreased to 56 u/ml and CEA to 2.9 ng/ml. Unfortunately, by the seventh months of therapy the patients tumor markers began to rise although the patient remained assymptomatic (CA 19-9 or 82). Finally, during the eighth month of therapy the patient’s pain returned and therapy was discontinued.

Conclusion:

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BIOCHEMICAL AND HEMATOLOGICAL CHANGES

OF CANCER PATIENTS AFTER WBH

Kurpeshev, O.; Pavlov, V.; Smirnova, I.

Medical Radiologicai Research Centre; Rams, Russia

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CAVITATION - IS IT POSSIBLE AFTER HYPERTERMO-
RADIOTHERAPY IN THE MUCOSITIS?

Ljubenov, T.

Clinical Centre of Nuclear Medicine and Radiotherapy -
Med. University Sofia, Bulgaria

When the radiolysis of the extra- and intra-cellular fluid begins and other chemical reactions, with the thermoradiobiological processes, then are formed the so-called cavitation under the mucous membrane in the oral cavity. Cavitation (small bubbles) is a violated homogeneity of a fluid as a result of the hydrodynamical change after local hyperthermia and radiotherapy, in which the pressure reaches a critical value of decrease and the number of the bubbles, full of gas or vapor, grows unlimitedly. In vivo measurement show the importance of the obtained specific absorption rate (SAR in mW/g) for the temperature elevation dT. Therefore, by further increasing heating for this specific SAR selection, an overheating of mucosa (often near the tumor because of too strong focusing) is treatment limiting. For characteristics of such small bubble we introduce the parameters p₀ (the pressure in it), r (the radius of the bubble) and p (the density of the which is found in the bubble). The conditions necessary for appearance of a destructive trace of the bubble (so-called cavitational erosion or ulceration in the epithelium) are:

semispherical form and adhesive to the mucosa,

b) the bubble is far away from the mucosa, etc. The time (T) and the velocity (v) of the embryonic formation of the bubbles we can denote with formula:

T= (P/P_o)^½ . r or V=r/T=(P/P_o)^½

18

THE BIRTH AND DEATH OF A HYPERTHERMANOLOGIST

McLaren, J., M.D.

Emery University Medical School

NCI conference and proceedings circa 1978

Leveen’s article in JAMA-c 1979

Bicher’s article in Yellow Journal –circa 1979

Holt’s publication of 40+ patients treated with cobalt 60 alone, +HBO, +HEAT

a) Hornbach’s – visit

b) Caldwell’s –visit

Caldwell’s TIE-IT-TOGETHER conference at the

University of Wisconsin in Madison

My visit to Leveen’s and Hornbach’s-Shidia’s facilities

Bicher’s first NAGH meeting in Detroit

Hornbach’s and Mclaren’s formation of a clinical

society- ICHS

Emory’s adventures into hypothermia with capacitance

and 434 MHz units with good physics support

The Harris company, BSD, Clinitherm, etc.

11. Emory’s purchase of Clinitherm Unit- primary for BPH

12. Concern of HSP’S –potential of HSP

FDA rules only reimbursement for heating superficial

lesions + radiation

The number of units in Atlanta drops from 6 to 0 which mirrors USA

Continued work off-shore of USA has kept hopes alive Possibly younger and brighter minds during the new millennium can put the physics and biological proven benefits of heat to clinical advantage!!!

19

MICROWAVE BALLOON CATHETERS FOR TREATING BPH

Mendecki, J.; Meiman, A.; Rechtescaffen, T. – Dept. of Urology Montefiore Medical Center, Bronx, New York , USA

Sterzer, F.; Mawhinney, D.; – MMTC; Princetoon, New Jersey, USA

F. Cheung, J. Mon – Celsion Corp.; Columbia, Maryland, USA

We have developed instrumentation which combines microwave heating with balloon dilatation to produce a biological stent in the urethra. This approach is designed to safely and effectively treat patients with BPH in a single session without anesthesia.

The basic innovation of this procedure is the use of modified Foley catheter which in addition to the anchoring balloon is equipped with a compression balloon at the level of its intraprostatic segment. The distention of this balloon is accomplished by means of circulating deionized water under pressure, which also provides cooling of the urethra during administration of hyperthermia.

During Phase 1 of the program, animal trials were performed on 11 dogs in whom thermocouples implanted directly into the prostate serviced to determine temperature levels necessary to produce dilatation of the prostatic urethra. With rectal and urethral temperature monitoring to maintain the safety range, an algorithm of temperature/power parameters needed for a safe and effective procedure has been established. Also a novel microwave radiometer for non-invasively monitoring subsurface tissue temp. during the microwave heating will be described. The method has now been tested successfully on 10 patients with BPH. Results of animal and clinical trials will be presented and discussed.

20

PORATION OF MALIGNANT TUMORS WITH MICROWAVE PULSES

Sterzer, F.; Mendecki, J.*, Friedenthal, E. #; Mawhinney, D.;

Meiman, A. *,

MMTC Inc. Princetoon, New Jersey, * Depart. Of
Urology, Albert Einstein College of Medicine, Bronx, New York, USA
# Rad. Oncol. Calvary Hospital Bronx, New York, USA

Electroporation is a process by which cell membranes are temporarily made more permeable by application of dc pulses to the tissue. One of the main sues of dc electroporation is to enhance the uptake by the targeted malignant cells of chemotherapeutic agents, particularly those with large molecules which normally are not able to penetrate the cellular membranes. Because dc poration techniques require contacting or implanted electrodes, the process is usually limited to the treatment of superficial tumors.

We have developed a non-invasive, clinically-usable method of microwave poration which permits to directly beam high peak power microwave pulses into target tissue. Our experiments were designed to assess the efficacy of the pulsed microwave signals in achieving in tumors poration effects equivalent to those produced to dc fields without the use of electrodes, thus allowing for non-invasive treatment of deep as well as superficial tumors. In a study on rats implanted with malignant prostate tumors we were able to demonstrate that the uptake of systemically administered high molecular weight fluorescein dextran (10,000D) was significantly and selectively increased by microwave pulsing of the tumors. A preferential uptake of such molecules by malignant tissue as compared with healthy tissue was also demonstrated.

21

THE COMBINATION OF CHEMOTHERAPY AND HIGH FREQUENCY HYPERTHERMIA IN GALL BLADDER CANCER

Migeod, F., M.D.; Douwes, F., M.D.

Klinik St Georg, Rosenheimerstr; Bad Aibling, Germany

46 patients (22 male, 24 female) with inoperable (n=39) or recurring (n=7) cancer of the gall bladder, bile duct or cholangiocellulary carcinoma were treated with a combined thermo-chemotherapy between September 1994 and January 1998. A local tumour as single location was found in 26/46 patients, additional metastases in 20/46 patients i.e. liver (n=16), peritoneum (n=11), lung (n=3), other (n=7). Patients with brain metastases were excluded. Median age was 63,3 years. All patients with gall bladder carcinoma had a history of gall bladder stones or resection. At the beginning of the treatment, 39/46 patients (85%) were taking analgesics i.e. opoids, NSAR. Chemotherapy included Mitomycin C, 8mg/m² day 1 & 3, folinate acid 200mg/m² i.v. day 1-5, & 5-FU 500mg/m² i.v. 2 hrs/day 1-5/4w, simultaneously with high frequency (13,56MHz) hyperthermia day 1, 3, 5, 8 & 10 (Oncotherm EHY system). In total 185 treatments regimes with 925 HF-hyperthermia were administered in the period mentioned above.

Sufficient temperatures were attained in 84,2% of all treatments carried out. Side effects for example, increase in pain during hyperthermia (9,3%), gastric symptoms (8,2%), fat tissue granuloma (4,3%) were observed. Thrombopenia occurred in all patients, n/e in 7/46 patients. Stomatitis in 10/46 patients and diarrhoea in 18/46 patients, WHO grade II / III. Pain reduction was observed in most patients (32/39), thus a reduction in analgesics quantity. CEA sensitivity in 25/46 patients, CA19-9 in 20/46 patients and a decrease in over 28 cases was observed. 70% objective responses in the primary or recurring sites (CT or NMR) were; 1/46 (CR), 17/46 (PR), 14/46 (MR/NC), progression in 14/46 patients (30%). The responders (CR + PR) time till progression was 11,2 months and survival 28,4+ months. In non-responders (PD), mostly those with metastased disease only 6,2 months was attained. The non-responding metastasing disease had a worse survival rate (6.2 months) than the non-responding local disease (9.0 months).

In conclusion, the hyperthermic effect is not only attained by heating, e.g. hypoxia and acidosis, but also by increasing intra-tumoural cytostatic effects and enhancing the immunological cytokine effects. The treatment is practical and tolerable, causing an encouraging rate of remissions and pain reduction, with minor complications.

22

THE EFFECTS OF HIGH FREQUENCY HYPERTHERMIA & COMBINED THERMO-CHEMOTHERAPY IN PLEURAL EFFUSIONS & ASCITES.

Migeod, F., M.D.,

Klinik St Georg, Rosenheimerstr; Bad Aibling, Germany

Pleural & pericardial effusions and ascites are often found in malignant diseases, especially in lung cancer, malignant lymphomas, mammarian cancer, acute leukemias, gynological & gastro-enterological tumors as gastric cancer. 40% of all pleural effusions, 20% of all pericardial effusions are of malignant origin, as well as 70% of all ascites. Commonly, effusions occur with a specific weight of <1016, protein over 30g/l.

The effect of a high frequency hyperthermia was investigated with regard to effusions with malignant cytology (Oncocare machine, Bruker system, 13,56MHz, 60 min., temperature over 21° C). Further investigations were carried out using a combined thermo-chemotherapy with the application of a mono-chemotherapy in to the effusion. The temperature was measured within the effusion by means of a fibre-optic system.

Reactions to therm-chemotherapy were seen in cases of gastric cancer, ovarian cancer, mammarian cancer and hypernephroma. The destructive effect from different hyperthermia temperatures was confirmed. We noticed an increased efficiency in cases where adjacent immune cells were found, especially in the dendritic type of myelomonocytic cell row (CD34). The dendritic reticulum cells play an important role in the processing and presentation of antigens to T-Cells. Pluripotent CD34 stem cells were collected by plasmapheresis (cell separator AS104, Fresenius Co.) These were taken to an ultra-violet photopheresis and reinstillated in the effusion to elevate cytotoxic activity.

23

THE COMBINATION OF CHEMOTHERAPY AND HIGH FREQUENCY HYPERTHERMIA IN PANCREATIC CANCER

Migeod, F., M.D.; Douwes, F., M.D.

Klinik St Georg, Rosenheimerstr; Bad Aibling, Germany

46 patients (27 male, 29 female) with inoperable (n=46) or recurring pancreatic cancer (n=9) were treated with a combined thermo-chemotherapy. Local tumour as single location was found in 26/46 patients, additional metastases for example, liver (n=19), peritoneum (n=20), lung (n=9), other (n=5), brain metastases were excluded from the study. Median age was 59.2 years. 73% of all patients were taking analgesics at the start of the treatment programme. Chemotherapy included Mitomycin C (8mg/m² day 1 & 3), folinate acid (200mg/m² i.v. day 1-5), & 5-FU (500mg/m² i.v. 2 hrs/day) simultaneously with high frequency (13,56MHz) hyperthermia days 1, 3, 5, 8 & 10 (Oncotherm EHY system, Germany) to the pancreas area. In total, 193 treatments regimes with 965 HF-Hyperthermias were administered between October 1993 and December 1996. Temperature control was achieved by duodenal probes. Sufficient temperatures were attained in 80.3% of all treatments carried out (42.1 - 44.0, median 42.5C). Side effects for example, increase in pain during hyperthermia (9.2%), gastric symptoms (12.4%), fat tissue granuloma (1.3%) were observed during the course of the treatment programme. Thrombpenia occurred in all patients, N/E in 8/46 patients, stomatitis in 10/46 patients and diarrhoea in 21/46 patients. Pain reduction was seen in patients with tumour pain, allowing for a reduction in analgesics quantity. CA19-9 sensitivity was attained in 41/46 patients. Objective responses in the primary and recurring sites (CT + NMR) were as follows: 1/46 patients (CR), 16/46 (PR), 22/46 patients (NC), 7/46 patients (PD). In time till progression (CR+PR) a period of 8.5 months and a survival of 16.1 months was observed in comparison to non-responders (PD) only 6.7 months. The non-responding metastased disease showed a worse survival rate (4.2 months) than local disease (9.0 months)

24

INTERSTITIAL HYPERTHERMIA AND PAIN CONTROL

Mykhalkin, I., M. D., Ph. D.

National Analytical Center, Medium, Institute of Experimental Pathology
Oncology and Radiobilogy Problems, Kiev, Ukraine

The treatment in clinics more than 200 patients established the regime based on pain feelings of the patient. The regime of control was decided for the following reasons:

1. Technical complexity of the installation of thermo-couples into the tumors.

2. Pain and psychotrauma of the thermo-couples installation procedure for the patient.

3. Less informative efficiency of thermo-monitoring after 2-3 procedures of hyperthermia with temperature measurement. Considerably frequent cases when thermo-couples are inserted into tumors presents a complicated operation (tumor of stomach, trachea). Necessity of temperature control with the regular tumor size control and big quantity of hyperthermia sets quite problematical. Pain feelings of patient is he isn’t scared of the procedure will determine efficacy of heating.

During the treatment of the malignant tumor, located up to 4 cm. under the skin experienced on dogs, heating was used by means of two tows of needles. The needles were inserted into the bottom and the top of the tumor. A distance between the needles is not more than 1 cm. in each row. The needles were supplied with a voltage of 1,73 Mhz frequency. The temperature was controlled in the center of the tumor and was kept during 60 min. on the level of 42-44C. In the area of the inserted needles it reached 50C. The dog was kept under narcoses. Applied technology allowed (due to high thermal dose) to kill the most livid and best blood supplied tumor ar4eas. After the first set of hyperthermia a regressivity of 50% was observed. 3 sets were sufficient for the total regressivity of the tumor for 5 dogs from each 9.

25

ALFA-INTEFERON AND CONTRICAL AS AN ADJUVANTS FOR HEAD
AND NECK CANCER THERMORADIOTHERAPY

Mykhalkin, I., M. D., Ph.D.; Bykow, V., M. D., Ph. D., Sc.D.;

Iashvilli, Z., M. D., Ph. D.

National Analytical Center, Medium Oncology Department of Institute of Otolaryngology, Kiev, Ukraine.

One hundred forty two patients with primary head and neck cancer were treated. Local microwave hyperthermia was achieved by electomagnetic field at 915 MHz with 0.5 to 0.6 W/cm square power density for the external heating technique and at 2450 MHz with 7 to 8 W/cm square power density for the intracavitary technique.

The local hyperthermia essentially increased the complete response of head and neck cancer. The using of inhibitor of proteolysis and interferon alone or together did not have influence on short-term reception.

The hyperthermia increased compared with radiation therapy alone by about 21%. No response in all groups with hyperthermia and adjuvant therapy hesitate about 14% and was not more than half of the data at group with radiation therapy alone. Our clinical investigations with inhibitor of proteolysis-contrical confirmed these data. Finally, the ajuvant therapy perhaps will play an important role in the primary radical treatment of cancer patients.

"Magnetron" from 1996 year used for treating of deep (200mm) located malignant tumors of brain, ovarian and intestinum, as report chef of Kyivs City Oncology Center’s Radiology Department. Result observed after second hyperthermia seance and bleeding stoppage of gynaecology organs tumors.

26

HYPERTHERMIA IN COMBINED TREATMENT OF HUMAN TUMORS

I. Mykhalkin M. D., Ph.D.; A. Gussev, Ph. D.; Yu. Medinets;
A. Mylianovskiy M. D., Ph.D., Sc. D.; V. Protsyk M. D., Ph.D.,Sc.D.;

V. Cherny M. D., Ph.D., Sc.D.
National Analytical Center, Kyiv City Oncology Center, Kyiv Medical Institute; Kiev, Ukraine

234 Patient with different tumor localizations have been treated combined with thermoradio- and chemotherapy. Tumor sites were as follows: rectum cancer 45, head and neck tumors 59, preinvasive cancer of the cervix with cervical neoplasia lesions 130. hyperthermia was administered using a microwave unit operating at 915 MHz power density 0.9-10 W/sq.m and 27.12 power density 0.3-10 W/sq. m (43C, 1h. after radiation). Hyperthermia was commenced within 1 an 1.5 h after the radiation. Antitumor drugs were given by infusion. Remission duration was enhanced by an average from 6 to 12 months, two years survival increased two-fold, three years 2-2.5 fold, five years 1.5-fold. The number of complications due to treatment use were not increased significantly, combined therapy was observed. The problems of hyperthermia application in combined treatment of oncologic patients are under investigation.

In some cases we used the rectal and vaginal changed applicators with condom. Magnetic hyperthermia irradiancer located in especial plastics stool. Irradiancer includes 1) Lamps ry-48 200 W (2ex), ry-49 (4 ex), ry-72 (4 ex) 2) transistor KT944A (4ex) KT956A, KT95\64A, KT980A, TT9126A, TT9131A,3) field-effect transistors KT1904A (4ex) KTI913A (4ex) 4) digital display AJIC331A (2ex) 3JIC345A (2ex) HB-nilJ 1-8113 5) printed thir-film microcircuit K176 (4ex) 6) capasitor K-50-35 (8ex), 7) cable PK-50-9-23 (10 feet) *) fiber-optical temperature measurement.

First step for one of best way for saving hyperthermia, our opinion, is producing a few thousand of cheap small hyperthermia irradience apparatus for every sweet home in USA, united European states, Australia, United Arabic Emirates, etc. (not for Canned, Ukraine, Russia etc. states with government medical care system) and giving possibility to say and work for progressive non-conservative scientists.

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THERMOREGULATORY MECHANISM IN THE MALIGNANT CARCINOMA TREATMENT BY ELECTROMAGNETIC HYPERTHERMIA COMBINED WITH RADIOCHEMOTHERAPY

Mykhalkin, I., M. D., Ph. D.

National Analytical Center Medium, Institute of Oncology; Kiev, Ukraine

Electromagnetic hyperthermia with radiation therapy and chemotherapy were carried out in 165 patients with malignant tumors. Analogous experimental investigations were accomplished on mice, rats and dogs. Rehabilitation of patients was accelerated, rate of irradiation reaction was dimensioned and terms of treatment of the patients were shortened. In addition the delay of transplanted tumors growth and the increasing of lifetime of animals were achieved. Various methods of electromagnetic hyperthermia make quite different structures of heat productions of heterogeneous tissue. Microwave heating supplies the zone of effective heat production in muscular tissue as deep as 2-4cm., with maximum of the heat production on the surface of skin.

Usage of strong heating makes the patients to feel pain. Application of coolers are widely used in electromagnetic hyperthermia. The heat receptors do not react with pain. Our cancer patients sensed some discomfort, the feeling of pressure in the tissue or could not express their feeling under electromagnetic hyperthermia.

The temperature in the tumor may go as high as 47 degree Celsius. The muscular tissue temperature goes up to 41-43 degree Celsius because of intensive blood circulation. The use of in inductive heating with the help of changing magnetic field gives the maximum heating influence to the tissue obtaining much liquid. That’s why the implementation of the inductive method is very effective in case of the tumors of soft tissue. Together with the mediLAK Company we worked out inductive irradiators with low level of heating. They undergo some approbation in oncological and orthopedy clinics in Kyiv and analongs of our irradiators from 1993 in Japan. Such irradiators are especially effective when used to treat different inflammation diseases.

28

HYPERTHERMIA TREATMENT OF INFLAMMATORING DISEASE

Mykhalkin, I., M. D., Ph.D.

National Analytical Center, Medium; Kiev, Ukraine

At present the application in oncology of electromagnetic hyperthermia with the aim of treat of different tumors is being widely spread. Using electromagnetic hyperthermia in heat production takes place in tissue volume, while they are oriented on heat transmission. That was the reason of our investigation of thermoregulatory reaction of tissue after using electromagnetic hyperthermia. In radio-frequent capacitive heating the spread of heating depends on the ingredients and configuration of the heating tissue. The bone and fat tissue are being mostly heated under such type of heating. The thermoregulatoring system in the bone tissue is absent, the fat layer plays the thermoregulating in the body. That’s why in treating the bones sarcoma this method is rather effective.

Our experience in application of radiofrequency irradiators showed high efficiency for treatment of inflammatory disease of throat, lungs, woman genitals, chronical sinusitis. Application of liver heating showed a high efficiency for improvement of its function in the rehabilitative period after hepatitis.

The average temperature is calculated taking in to account time of being applied. The highest thermoproduction is usually concentrated in the area nearest to the radiator of the tumor. The temperature inside of the tumor during the hyperthermia is quire irregular. The temperature of the difference points of the tumor can be defined also by the velocity of the heat flow of the bloodstream. That is why in the narcotized point of the tumor the temperature is higher than in others. The lower temperature appears in the farthest point of the tumor with high blood stream intensity, the low level of thermoproduction appears in this area as well.

Therefore, in our opinion, on the thermal dose chart, the tumor should be divided into several areas. The most intensive monitoring should be done in the less heated areas. The less intensive monitoring should be done in the necrosis area. Thermal dose should be calculated separately for every point. An averaging of the thermal dose, on our opinion, will only distort the real picture of the heat action efficiency.

29

OVERVIEW OF HYPERTHERMIA PHYSICS

Gilbert H. Nussbaum, Ph.D.; Mallinckrodt Institute of Radiology

Washington University School of Medicine
St. Louis, Missouri, USA

While the biological and physiological rationale for utilizing hyperthermia in the treatment of cancer is sound, the administration of satisfactory thermotherapy is often quite challenging. The induction and maintenance of clinically prescribed temperature elevation in targeted tissue requires that the methods employed for deposition of power and determination of temperature in-vivo be appropriate to the treatments given. This overview will identify and briefly discuss the factors governing tissue heating, i.e., energy balance, bioheat equation, specific absorption rate and perfusion rate. Characteristics of power deposition by microwaves, ultrasound and rf electric currents will be summarized. Techniques and clinical applications of interstitial hyperthermia will be discussed, as will performance characteristics of various heating applicators and thermometers.

30

"INORGANIC" COBALT(III) COMPLEXES WITH TETRADENTATE SCHIFF BASES AND BIOGENIC NITROUS BASES AS A NEW ANTICANCER AGENTS WITH RADIO/THERMOSENSITIZING ACTIVITIES

Osinsky S.¹, Levitin I.², Bubnovskaya L.¹,Sigan A.²,Ganusevich I.¹

POTENTIAL EFFECTS OF HYPERTHERMIA ON ENZYMATIC ACTION IN CANCER THERAPY

Pigliucci. G.M.; *Ercole P.; *Campanella. L.

University of RomeTOR VERGATA, Department of Surgery ; Italy
*University of Rome LA SAPIENZA, Chemistry Department ; Italy

Many Authors have demonstrated the therapeutic effects of hyperthermia in cancer treatment. Particularly, microwave or radiofrequency hyperthermia (41.5- 42.0 C°) increase the effects of other traditional approaches such radio and chemotherapy with an elective action on neoplastic cells avoiding relevant side effects on healthy tissues.

Our study has underlined the relationship between some experimental results and the more accredited theories about the action of heat on tumoral cells (sensitivity increased by the hypoxic methabolism of tumoral cell and the induction of a stop in DNA replication). Heat seems enhance some enzymatic mechanism that neutralise cancerogenic environmental pollutants accumulated in neoplastic cells like Benzene. This results could suggest a possible role for enzymatic defect in the origin of malignancies. The defect could be congenital or acquired for functional modification produced by different causes, included infectious disease.

This hypothesis, that undoubtedly needs of more experimental and clinical confirmations above all about the different tumoral hystotype, suggest a new way in cancer treatment based on enzymatic activity modulation.

In this context, hyperthermia can play a significant role as an easy and safe modulating agent.

REFERENCES

1) R. Fiorito, G.M. Pigliucci, D. Venditti, B. Iorio, F. Giudiceandrea, V. Cervelli, V. Vittorini, C.U. Casciani.

Efficacy of hyperglycemia to increase the effects of radiotherapy and thermoherapy.

Progresso Medico, 46: 57, 1990 Roma.

2) G.M. Pigliucci, F. Giudiceandrea, D.Venditti, V. Cervelli e Casciani C.U.

Optimization of Pre-Intra and Postoperative Hyperthermic treatment in Inoperable Lower Bowel and Liver Tumors.

Oncology, 50, 390-92, 1993.

3) G.M. Pigliucci, B. Iorio, D. Venditti, R. Fiorito, V. Cervelli, V. Vittorini, F. Giudiceandrea and C.U. Casciani.

The thermotherapy: A method increasing the effect of multidisciplinary treatment of cancer.

The 2nd All-Union Symposium with International Participation Hyperthermia in Oncology

Minsk, Urss, May 30-31, 1990

34

4) Pigliucci G.M., Venditti D., Giudiceandrea F., Maggiulli G., Cervelli V., Campioni M., Pisani A., Cervelli G., Iorio B. Casciani C.U.

Un Moderno approccio terapeutico nei tumori inoperabili del fegato: l'associazione chemio-embolizzazione distrettuale ed ipertermia.

Atti del 95 Congresso nazionale della Societa' Italiana di Chirurgia, Milano, 17-20 ottobre, 1993.

5) Pigliucci GM, Pochini M, Giudiceandrea F, Maggiulli G, Cervelli V, Casciani CU, Diamantini S, Fox U.

Our experiences and new perspective in interstitial microwave hyperthermia.

Abstract Book 18th International Symposium on Clinical Hyperthermia,

may 21-24 1995, Kiev, Ukraine.

35

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.

36

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.

37

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

38

39

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.

40

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.

41

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.

42

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.

43

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

44

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.

45

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.

46

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.

47

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

48

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.

49

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.

50

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 (cm²) (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.

51

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

52

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 44E 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%)

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.