Microwave thermochemotherapy in the treatment of the bladder carcinoma--electromagnetic and dielectric studies--clinical protocol.

Microwave thermotherapy is currently used in clinical routines for benign prostatic hyperplasia treatments. The temperature increase is obtained using an endocavitary microwave applicator placed in the prostatic urethra. This urethral applicator after a technical modification can be placed inside the bladder in order to potentiate the effects of the treatment by chemotherapy of vesical carcinoma. This paper deals with electromagnetic studies of this new endocavitary applicator. First of all, the experimental determination of the dielectric permittivities for the propagation domain characterization is achieved in order to be used in the electromagnetic model. Compared to experimental results, these simulations obtained by the finite-difference time-domain formalism allow us to determine the electromagnetic performance of this applicator. Finally, the in vivo study realized on anesthetized dogs to determine the therapeutic protocol associating chemotherapy and thermotherapy in the treatment of the bladder cancer is presented.

New 434 MHz interstitial hyperthermia system monitored by microwave radiometry: theoretical and experimental results.

A new complete microwave interstitial hyperthermia system monitored automatically by microwave radiometry and working at 434 MHz is described in this paper. This system, which includes a new radiometer with two internal temperature references, is detailed. All its characteristics for microwave heating and radiometry are presented. The new possibilities are shown through numerous experiments on acrylamide phantom and excised tissues, which have been carried out for different antennae implantation corresponding to the clinical situation. The clinic protocol, associate to the brachytherapy, imposes the use of semi-loop catheters. Coaxial antennae, inserted in these catheters, are not, therefore, positioned in a rectilinear manner but undergo a curve. So, models based on the FDTD formalism are developed to determine the theoretical power deposition. Owing to these models, the effects of this physical motive on radiation diagrams can be taken into account. The results of the power deposition are presented for two antennae. Thermal patterns can then be determined by the solution of the bioheat-transfer equation in the steady state. Also, the comparison of the results given by the new interstitial hyperthermia system with those obtained with the previous 915 MHz one shows an improvement of the thermal performances.

[Study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrences of superficial tumors of the bladder]. / Etude de la synergie hyperthermie micro-onde/chimiothérapie intravésicale dans la prévention des récidives des tumeurs superficielles de vessie.

OBJECTIVES: Preliminary clinical studies of the combination of hyperthermia and intravesical chemotherapy indicated very encouraging results in favour of multidisciplinary treatment of recurrent superficial bladder tumours. The authors studied the in vitro and early in vivo effects of this treatment. MATERIAL AND METHODS: An intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was controlled by two intravesical thermocouples and 4 transducers on the bladder wall. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological saline. Dogs were sacrificed after each one-hour session, and histological intravesical lesions were defined as grade 0, 1 or 2 corresponding to absence of lesions, or the presence of inflammatory lesions or urothelial lesions, respectively. In vitro, the first step consisted of creation of an immortalized tumour cell line from a grade II bladder papilloma. This HVT 196 cell line was incubated between 37 degrees C and 44 degrees C with increasing mitomycin concentrations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colorimetric method. RESULTS: In vivo, in 8 dogs, histological analysis of the comparative cytotoxicity of the various treatments confirmed the synergistic effect of heat and mitomycin C. In dogs treated at 45 degrees C, marked urothelial lesions were observed, regardless of the mitomycin C concentration. The in vitro comparative toxicity study on our cell line showed a much more intense cytotoxic effect with combined treatment than with cytostatic treatment alone. Expressed as the percentage of cytotoxicity compared to a control cell pool for a concentration of 1 microgram per ml. the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a cytotoxic effect of 8.4% and 98.41% respectively. CONCLUSION: A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations.

Study of the effects of thermotherapy in benign prostatic hypertrophy.

UNLABELLED: Prostatic transurethral thermotherapy was evaluated clinically using the Prostcare microwave system of the Bruker Company, which uses a microwave radiometer to measure and control intraprostatic temperature. OBJECTIVES: The aim of our study was to evaluate the immediate histological lesions induced in the prostatic tissue depending on the temperatures delivered to the prostate; the histological changes when adenectomy is carried out after thermotherapy, and the endoscopic appearance of the prostatic fossa 48 h, and 1, 2, 3 and 6 months after thermotherapy. METHODS: Our study was divided into three stages: in the first stage, we conducted thermotherapy in 10 patients in whom suprapubic adenectomy was indicated. During thermotherapy, a multipoint fiber-optic receptor and two thermocouples were implanted into the prostage gland at a distance of 5-15 mm from the urethra. Adenectomy was carried out 10 min after thermotherapy; the second stage of our study concerned the changes seen over time. We heated adenomas using the same protocol and carried out adenectomy 24, 48, 72 h, and 1 week, 6 weeks and 3 months after thermotherapy, and lastly, we studied the endoscopic appearance after a single heating-session of 30 min by endoscopic controls at different times after thermotherapy (48 h, 1, 2, 3 and 6 months after thermotherapy). RESULTS: Macroscopic appearance: necrotic lesions measured 30 mm in length on average. Necrosis was roughly circumferential. Immediate histological aspect: in all cases, histological examination showed coagulation necrosis with periurethral thromboses. Histological changes: at 8 days, necrosis intensity was maximal and histological structures were difficult to identify. Endoscopic appearance: 3 months after thermotherapy, the typical endoscopic appearance was a large periurethral cavity. There was a sharp demarcation between untreated areas and cicatricial tissue. CONCLUSION: The efficacy of thermotherapy depends on the radiometric temperature, which should reach 47 degrees C (i.e. a temperature of 55-65 degrees C delivered to the prostate), and a rapid increase in temperature, i.e. in the power applied, which should reach the thermal radiometric level of 47 degrees C in 5 min. As soon as necrosis is obtained, the power is automatically reduced. Using this protocol, heating proves effective in 30 min.

915 MHz microwave interstitial hyperthermia. Part I: Theoretical and experimental aspects with temperature control by multifrequency radiometry.

Microwave interstitial hyperthermia now plays an increasing part in the various hyperthermia techniques used in cancer treatment. This paper will present the design, construction and theoretical as well as experimental study of miniature coaxial antennas designed to heat tumours of various volumes and sizes. Monitoring temperature using multifrequency radiometry during hyperthermia stems naturally from the very design of these antennas. Experiments on phantoms, animals and patients in phase I clinical assessment have demonstrated that microwave interstitial hyperthermia can be achieved with temperature control and monitoring by microwave radiometry.

Non-invasive microwave multifrequency radiometry used in microwave hyperthermia for bidimensional reconstruction of temperature patterns.

Microwave radiometry, used routinely since 1984 for non-invasive temperature measurements during hyperthermia sessions for superficial tumours treatment has proven its efficiency for temperature control. From radiometric temperature measurements in two frequency ranges (around 1 and 3 GHz) and superficial (or cutaneous) temperature measurements achieved during hyperthermia sessions, a numerical method to obtain the two-dimensional thermal profile has been developed and implemented. This method is based on hyperthermia simulation from the bioheat equation, the absorbed microwave power calculation in the medium taking into account the radiative diagram of the applicator, and the calculation of radiometric temperatures. From these experimental measurements (radiometric and superficial temperatures, heating power, dielectric and thermal characteristics), a program to determine the bidimensional distribution of temperature during the hyperthermia session has been developed, tested and used during and after clinical treatments.

915 MHz microwave interstitial hyperthermia. Part III: Phase II clinical results.

From October 1989 to October 1991, 16 patients (17 tumours) with locally advanced carcinomas of the oral tongue and eight patients with second carcinomas of the base of tongue in previously irradiated areas, have been treated by means of an interstitial hyperthermia-brachytherapy combination in a phase II clinical trial. Each miniature microwave antenna of our hyperthermia system, called HIMCAR, is used both for heating and for thermal measurements by microwave radiometry at 3 and 9 GHz (see Part I). Among these 25 lesions (21 T2, 4 T3), 21 showed a complete response (15/17 locally advanced carcinomas and 6/8 second carcinomas in previously irradiated areas). The toxicity was not severe (less than 10%). A French multicentre phase III study is now under way.

915 MHz microwave interstitial hyperthermia. Part II: Array of phase-monitored antennas.

In order to heat the whole volume of a tumour by microwave interstitial hyperthermia it is necessary to use an antenna array. The antenna modelization and the numerical solution of the bidimensional bioheat transfer equation allow determination of temperature evolution during a heating session. The calculations are taken for four antennas fed in phase and the theory is then proven by experiments on gel and on patients. Results are presented on cross-section heating patterns and their time evolution. Temperature distribution is calculated when feeding one antenna by a feeding current out of phase with the other currents. The phase difference value is optimized and it is then demonstrated that the heated volume is increased by successively feeding each antenna with an out-of-phase current. The time taken to feed each antenna one after the other is optimized.

Transurethral thermotherapy of the benign prostate hypertrophy controlled by radiometry.

Up to now control of the microwave heating of the prostate was only possible with rectal or urethral surface catheters. This problem has finally been solved with the help of the Prostcare apparatus (Bruker Spectrospin, Wissembourg, France) and radiometry: the prostate can be treated by the urethral or endorectal route with a 915-MHz generator and coaxial antennae, a unique device which allows us to measure real intraprostatic temperature, to regulate the microwave emission power and to eliminate classic surface controls. A sole antenna is used for the urethral catheter; it is introduced within the Foley-type probe and allows us to heat and measure the heat (radiometry). In this preliminary report, we present clinical results of the first 105 treated patients over 18 months by the transurethral route in a single 1-hour session: 7 have a protuberant median lobe and the treatment is without any effect; 76 patients can be analyzed and the Madsen score before treatment, at 3 months and at 6 months moves from 11.2 to 2.5 and 3.1, the maximum flow rate from 9.6 to 12.3 and 12.5 ml/s, the residue decreases from 102 to 68 and 53 ml. The session is well tolerated and patients mention that the effects are better than those of medical treatment. Hyperthermia is a simple method that will find its place between medical and surgical treatment once the numerous randomized studies have determined the most suitable therapeutic procedures.

A new method for thermal dosimetry in microwave hyperthermia using microwave radiometry for temperature control.

Microwave radiometry has been used during the last few years in some clinical centres (Lille, Freiburg, Strasbourg, Brussels) for the non-invasive control of temperature during microwave hyperthermia. The principal objective of this paper is to present an atraumatic thermal dosimetry system based on numerical simulations of hyperthermia and radiometric temperature measurements for TEM propagation. To gauge the feasibility and performance of the method, a one-dimensional model in a homogeneous medium is considered, neglecting the curvature of the tissue layer. The good correlation between the theoretical and experimental values obtained allowed the likely thermal profile on the probe axis to be computed using the dielectric and thermal properties of the medium and measurement of the radiometric and cutaneous temperatures.

Microwave hyperthermia controlled by microwave radiometry: technical aspects and first clinical results.

Microwave systems combining microwave heating generators (434, 915 or 2450 MHz) with microwave radiometers (1-2 GHz or 2-4 GHz) have been used for two years in hyperthermia therapy. Technical aspects (generator, radiometer, applicator), experiments and first clinical results are detailed.

Microwave thermography--characteristics of waveguide applicators and signatures of thermal structures.

In this paper, we study the problem of the interpretation of the signals provided by microwave thermography, which allows the detection of the thermal gradients in living tissues. These signals correspond to the thermal noise measured by a radiometer when the probe scans the surface of the tissues (passive process). We describe how these signals can be computed by means of a new method based on the antenna reciprocity principle. This process requires a knowledge of the electrical field distribution in the lossy medium when the applicator is radiating a microwave signal (active process). Examples of computations of the thermal signals and experimental verifications are presented. Then, we introduce a new concept of 'thermal signature' and show how it is possible to reach a quantitative interpretation of the thermal signals such as those obtained in clinical investigations (thermal pattern recognition).

Electrical characteristics of waveguide applicators for medical applications.

This work concerns the electrical properties of waveguide applicators consisting of flanged rectangular waveguides filled with a dielectric, used in medical applications (microwave thermography and local hyperthermia). The reflection coefficient and the near field configuration in lossy materials were obtained in some cases analytically and in some other cases numerically. The validity of these methods was verified experimentally. The study shows that the matching of the applicator and the penetration depth in a lossy material, such as a living tissue, depend not only on the tissue characteristics but also on the characteristics of the applicator itself.