Overview of bladder heating technology: matching capabilities with clinical requirements.

Moderate temperature hyperthermia (40-45°C for 1 h) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle-invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle-invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of the bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled radio-frequency current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC

An Electromagnetic Head and Neck Hyperthermia Applicator: experimental phantom verification and FDTD model

Purpose: To experimentally verify the feasibility of focused heating in the neck region by an array of two rings of six electromagnetic antennas. We also measured the dynamic specific absorption rate (SAR) steering possibilities of this setup and compared these SAR patterns to simulations. Methods and Materials: Using a specially constructed laboratory prototype head-and-neck applicator, including a neck-mimicking cylindrical muscle phantom, we performed SAR measurements by electric field, Schottkydiode sheet measurements and, using the power-pulse technique, by fiberoptic thermometry and infrared thermography. Using phase steering, we also steered the SAR distribution in radial and axial directions. All measured distributions were compared with the predictions by a finite-difference time-domain–based electromagnetic simulator. Results: A central 50% iso-SAR focus of 35 +/- 3 mm in diameter and about 100 +/- 15 mm in length was obtained for all investigated settings. Furthermore, this SAR focus could be steered toward the desired location in the radial and axial directions with an accuracy of ~5 mm. The SAR distributions as measured by all three experimental methods were well predicted by the simulations. Conclusion: The results of our study have shown that focused heating in the neck is feasible and that this focus can be effectively steered in the radial and axial directions. For quality assurance measurements, we believe that the Schottky-diode sheet provides the best compromise among effort, speed, and accuracy, although a more specific and improved design is warranted

Comparison of intratumor and intraluminal temperatures during locoregional deep hyperthermia of pelvic tumors

Purpose: To investigate whether intraluminal thermometry provides sufficient information to apply high quality deep hyperthermia in pelvic tumors. Patients and Methods: The intratumor and intraluminal temperatures of 48 patients were analyzed per cancer type: rectum (21 male, 14 female), cervix (n = 8), and bladder (n = 5). Temperature-dose parameters were calculated, temperature curves within each treatment session were compared, and correlation between intratumor and intraluminal temperatures was analyzed. Results: Intratumor and intraluminal temperatures at the same time points during individual treatments were highly correlated (mean correlation coefficient: 0.93). However, the quantitative level differed from 0.1 to 1.1 degrees C and the differences of the timetemperature graphs varied per tumor group. Average intratumor and intraluminal temperatures were not different in the four groups. Intratumor thermometry was found not superior over intraluminal thermometry to improve tumor temperature level and homogeneity by SAR steering. Conclusion: Intraluminal thermometry provides sufficient information to apply deep hyperthermia to individual patients with centrally located rectum, cervix or bladder cancer

A moderate thermal dose is sufficient for effective free and TSL based thermochemotherapy

Hyperthermia, i.e. heating the tumor to a temperature of 40–43 °C is considered by many a valuable treatment to sensitize tumor cells to radiotherapy and chemotherapy. In recent randomized trials the great potential of adding hyperthermia to chemotherapy was demonstrated for treatment of high risk soft tissue sarcoma: +11.4% 5 yrs. overall survival (OS) and for ovarian cancer with peritoneal involvement nearly +12 months OS gain. As a result interest in combining chemotherapy with hyperthermia, i.e. thermochemotherapy, is growing. Extensive biological research has revealed that hyperthermia causes multiple effects, from direct cell kill to improved oxygenation, whereby each effect has a specific temperature range. Thermal sensitization of the tumor cell for chemotherapy occurs for many drugs at temperatures ranging from 40 to 42 °C with little additional increase of sensitization at higher temperatures. Increasing perfusion/oxygenation and increased extravasation are two other important hyperthermia induced mechanisms. The combination of free drug and hyperthermia has not been found to increase tumor drug concentration. Hence, enhanced effectiveness of free drug will de

A head and neck hyperthermia applicator: Theoretical antenna array design

Purpose: Investigation into the feasibility of a circular array of dipole antennas to deposit RF-energy centrally in the neck as a function of: (1) patient positioning, (2) antenna ring radius, (3) number of antenna rings, (4) number of antennas per ring and (5) distance between antenna rings. Materials and Methods: Power absorption (PA) distributions in realistic, head and neck, anatomy models are calculated at 433 MHz. Relative PA distributions corresponding to different set-ups were analysed using the ratio of the average PA (aPA) in the target and neck region. Results: Enlarging the antenna ring radius from 12.5cm to 25 cm resulted in a ~21% decrease in aPA. By changing the orientation of the patients with respect to the array an increase by ~11% was obtained. Increase of the amount of antenna rings led to a better focussing of the power (1 - 2 / 3: ~17%). Increase of the distance between the antenna rings resulted in a smaller (more target region conformal) focus but also a decreased power penetration. Conclusions: A single optimum array setup suitable for all patients is difficult to define. Based on the results and practical limitations a setup consisting of two rings of six antennas with a radius of 20 cm and 6 cm array spacing is considered a good choice providing the ability to heat the majority of patients

Assessment of the local SAR Distortion by Major Anatomical Structures in a Cylindrical Neck Phantom

The objective of this work is to gain insight in the distortions on the local SAR distribution by various major anatomical structures in the neck. High resolution 3D FDTD calculations based on a variable grid are made for a semi-3D generic phantom based on average dimensions obtained from CT-derived human data and in which simplified structures representing trachea, cartilage, spine and spinal cord are inserted. In addition, phantoms with dimensions equal to maximum and minimum values within the CT-derived data are also studied. In all cases, the phantoms are exposed to a circular coherent array of eight dipoles within a water bolus and driven at 433 MHz. Comparisons of the SAR distributions due to individual structures or a combination of structures are made relative to a cylindrical phantom with muscle properties. The calculations predict a centrally located region of high SAR within all neck phantoms. This focal region, expressed as contours at either 50% or 75% of the peak SAR, changes from a circular cross-section in the case of the muscle phantom to a doughnut shaped region when the anatomical structures are present. The presence of the spine causes the greatest change in the SAR distribution, followed closely by the trachea. Global changes in the mean SAR relative to the uniform phantom are <11%, whilst local changes are as high as 2.7-fold. There is little difference in the focal dimensions between the average and smallest phantoms, but a decrease in the focal region is seen in the case of the largest phantom. This study presents a first step towards understanding of the complex influences of the various parameters on the SAR pattern which will facilitate the design of a site-specific head and neck hyperthermia applicator

A Patch Antenna Design for Application in a Phased-Array Head and Neck Hyperthermia Applicator

In this paper, we describe a specifically designed patch antenna that can be used as the basis antenna element of a clinical phased-array head and neck hyperthermia applicator. Using electromagnetic simulations we optimized the dimensions of a probe-fed patch antenna design for operation at 433 MHz. By several optimization steps we could converge to a theoretical reflection of -38 dB and a bandwidth (-15 dB) of 20 MHz (4.6%). Theoretically, the electrical performance of the antenna was satisfactory over a temperature range of 15 C–35 C, and stable for patient-antenna distances to as low as 4 cm. In an experimental cylindrical setup using six elements of the final patch design, we measured the impedance characteristics of the antenna 1) to establish its performance in the applicator and 2) to validate the simulations. For this experimental setup we simulated and measured comparable values: -21 dB reflection at 433 MHz and a bandwidth of 18.5 MHz. On the basis of this study, we anticipate good central interference of the fields of multiple antennas and conclude that this patch antenna design is very suitable for the clinical antenna array. In future research we will verify the electrical performance in a prototype applicator

Current state of the art of regional hyperthermia treatment planning: A review

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve locoregional heating. This paper reviews the developments in treatment planning software for tissue segmentation, electromagnetic field calculations, thermal modeling and optimization techniques. Over the last decade, simulation tools have become more advanced. On-line use has become possible by implementing algorithms on the graphical processing unit, which allows real-time computations. The number of applications using treatment planning is increasing rapidly and moving on from retrospective analyses towards assisting prospective clinical treatment strategies. Some clinically relevant applications will be discussed

SAR thresholds for electromagnetic exposure using functional thermal dose limits

Background and purpose: To protect against any potential adverse effects to human health from localised exposure to radio frequency (100 kHz–3 GHz) electromagnetic fields (RF EMF), international health organisations have defined basic restrictions on specific absorption rate (SAR) in tissues. These exposure restrictions incorporate safety factors which are generally conservative so that exposures that exceed the basic restrictions are not necessarily harmful. The magnitude of safety margin for various exposure scenarios is unknown. This shortcoming becomes more critical for medical applications where the safety guidelines are required to be relaxed. The purpose of this study was to quantify the magnitude of the safety factor included in the current basic restrictions for various exposure scenarios under localised exposure to RF EMF. Materials and methods: For each exposure scenario, we used the lowest thermal dose (TD) required to induce acute local tissue damage reported in literature, calculated the corresponding TD-functional SAR limits (SARTDFL) and related these limits to the existing basic restrictions, thereby estimating the respective safety factor. Results: The margin of safety factor in the current basic restrictions on 10 g peak spatial average SAR (psSAR10g) for muscle is large and can reach up to 31.2. Conclusions: Our analysis provides clear instructions for calculation of SARTDFL and consequently quantification of the incorporated safety factor in the current basic restrictions. This research can form the basis for further discussion on establishing the guidelines dedicated to a specific exposure scenario, i.e. exposure-specific SAR limits, rather than the current generic guidelines

Assessment of the thermal tissue models for the head and neck hyperthermia treatment planning

Purpose: To compare different thermal tissue models for head and neck hyperthermia treatment planning, and to assess the results using predicted and measured applied power data from clinical treatments. Methods: Three commonly used temperature models from literature were analysed: “constant baseline”, “constant thermal stress” and “temperature dependent”. Power and phase data of 93 treatments of 20 head and neck patients treated with the HYPERcollar3D applicator were used. The impact on predicted median temperature T50 inside the target region was analysed with maximum allowed temperature of 44 °C in healthy tissue. The robustness of predicted T50 for the three models against the influence of blood perfusion, thermal conductivity and the assumed hotspot temperature level was analysed. Results: We found an average predicted T50 of 41.0 ± 1.3 °C (constant baseline model), 39.9 ± 1.1 °C (constant thermal stress model) and 41.7 ± 1.1 °C (temperature dependent model). The constant thermal stress model resulted in the best agreement between the predicted power (P = 132.7 ± 45.9 W) and the average power measured during the hyperthermia treatments (P = 129.1 ± 83.0 W). Conclusion: The temperature dependent model predicts an unrealistically high T50. The power values for the constant thermal stress model, after scaling simulated maximum temperatures to 44 °C, matched best to the average measured powers. We consider this model to be the most appropriate for temperature predictions using the HYPERcollar3D applicator, however further studies are necessary for developing of robust temperature model for tissues during heat stress.</p