Heating technology for malignant tumors: a review

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 degrees C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 degrees C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors

Desarrollo de un nuevo sistema de hipertermia de microondas para aplicaciones

[ENG]Microwave technology is now widely used in a variety of medical applications such as cancer treatment and diagnostics. This project describes the structure of a novel hyperthermia system for biomedical research. The software Ansoft HFSS was used to design a rectangular waveguide applicator. A closed-loop is presented in order to control the output power of the system by the temperature measured on the sample. Initial results from experimental testing are presented. In these results, it is shown that the water temperature can be increased from 21ºC to 40ºC in 12 minutes. Therefore, it has been tested that the system works properly. The next step would be to apply the system to melanoma cancer cells. [SPA]Ya existen tecnologías que implican el uso de microondas en una gran variedad de aplicaciones m édicas tales como el diagnóstico y el tratamiento del cáncer. Este proyecto describe la estructura de un nuevo sistema de hipertermia para ser usado en todo tipo de investigaciones biom édicas. El software Ansoft HFSS ha sido usado para diseñar una guía de onda rectangular que ser á el componente final al que se aplicar á nuestro sistema. Además, se dispone de un bucle cerrado en el propio sistema para poder controlar la potencia de salida en función de la temperatura medida en la muestra. Los resultados iniciales del experimento se han presentado en este documento. En estos resultados, se muestra que la temperatura del agua puede ser incrementada desde 21ºC hasta 40ºC en unos 12 minutos. Por lo tanto, se ha comprobado que el sistema funciona de forma adecuada. El siguiente paso ser a aplicar el sistema directamente sobre c elulas cancer genas.Escuela Técnica Superior de Ingeniería de TelecomunicaciónHeriot Watt UniversityUniversidad Politécnica de Cartagen

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Towards UWB microwave hyperthermia for brain cancer treatment

Despite numerous clinical trials demonstrating that microwave hyperthermia is a powerful adjuvant modality in the treatment of cancers, there have been few instances where this method has been applied to brain tumors. The reason is a combination of anatomical and physiological factors in this site that require an extra degree of accuracy and control in the thermal dose delivery which current systems are not able to provide. All clinical applicators available today are in fact based on a single-frequency technology. In terms of treatment planning options, the use of a single frequency is limiting as the size of the focal spot cannot be modified to accommodate the specific tumor volume and location. The introduction of UWB systems opens up an opportunity to overcome these limitations, as they convey the possibility to adapt the focal spot and to use multiple operating frequencies to reduce the power deposition in healthy tissues.In this thesis, we explore whether the current treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for UWB microwave hyperthermia. We analyze the most commonly used cost-functions for treatment planning optimization and discuss their suitability for use with UWB systems. Then, we propose a novel cost-function specifically tailored for UWB optimization (HCQ). To solve for the HCQ, we further describe a novel, time-reversal based, iterative scheme for the rapid and efficient optimization of UWB treatment plans. We show that the combined use of these techniques results in treatment plans that better exploit the benefits of UWB systems, yielding increased tumor coverage and lower peak temperatures outside the target. Next, we investigate the design possibilities of UWB applicators and introduce a fast E-field approximation scheme. The method can be used for the global optimization of the array parameters with respect to the multiple objectives and requirements of hyperthermia treatments. Together, the proposed solutions represent a step forward in the implementation of patient-specific hyperthermia treatments, increasing their accuracy and precision. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible, and motivate the efforts for further development of UWB applicators and systems

In Vitro Examinations of Cell Death Induction and the Immune Phenotype of Cancer Cells Following Radiative-Based Hyperthermia with 915 MHz in Combination with Radiotherapy

Multimodal tumor treatment settings consisting of radiotherapy and immunomodulating agents such as immune checkpoint inhibitors are more and more commonly applied in clinics. In this context, the immune phenotype of tumor cells has a major influence on the anti-tumor immune response as well as the composition of the tumor microenvironment. A promising approach to further boost anti-tumor immune responses is to add hyperthermia (HT), i.e., heating the tumor tissue between 39 °C to 45 °C for 60 min. One key technique is the use of radiative hyperthermia systems. However, knowledge is limited as to how the frequency of the used radiative systems affects the immune phenotype of the treated tumor cells. By using our self-designed in vitro hyperthermia system, we compared cell death induction and expression of immune checkpoint molecules (ICM) on the tumor cell surface of murine B16 melanoma and human MDA-MB-231 and MCF-7 breast cancer cells following HT treatment with clinically relevant microwaves at 915 MHz or 2.45 GHz alone, radiotherapy (RT; 2 × 5 Gy or 5 × 2 Gy) alone or in combination (RHT). At 44 °C, HT alone was the dominant cell death inductor with inactivation rates of around 70% for B16, 45% for MDA-MB-231 and 35% for MCF-7 at 915 MHz and 80%, 60% and 50% at 2.45 GHz, respectively. Additional RT resulted in 5-15% higher levels of dead cells. The expression of ICM on tumor cells showed time-, treatment-, cell line- and frequency-dependent effects and was highest for RHT. Computer simulations of an exemplary spherical cell revealed frequency-dependent local energy absorption. The frequency of hyperthermia systems is a newly identified parameter that could also affect the immune phenotype of tumor cells and consequently the immunogenicity of tumors

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

Laser Ablation and Immune Stimulating Interstitial Laser Thermotherapy

Based on nineteenth-century findings that showed that heat (fever) could be used to treat cancer, local hyperthermia has been developed as a tool to eradicate local tumors when surgical excision is deemed impossible. Nonetheless many cancer patients with advanced disease still lack effective treatment. During the last decades, data has emerged indicating that in situ destruction of tumors in some cases may induce tumor antigen release which can stimulate antigen-specific cellular immunity. Immune stimulating interstitial laser thermotherapy (imILT) is a method for local hyperthermia using laser light to increase tissue temperature with a specific protocol which can result in in situ vaccination. In vivo studies have shown that the method can induce an immune response that is effective against re-challenging, therefore indicating abscopal effect. Data was collected during clinical studies to assess the safety and feasibility of the method

Medical Laser-Induced Thermotherapy - Models and Applications

Heat has long been utilised as a therapeutic tool in medicine. Laser-induced thermotherapy aims at achieving the local destruction of lesions, relying on the conversion of the light absorbed by the tissue into heat. In interstitial laser-induced thermotherapy, light is focused into thin optical fibres, which are placed deep into the tumour mass. The objective of this work was to increase the understanding of the physical and biological phenomena governing the response to laser-induced thermotherapy, with special reference to treatment of liver tumours and benign prostatic hyperplasia. Mathematical models were used to calculate the distribution of light absorption and the subsequent temperature distribution in laser-irradiated tissues. The models were used to investigate the influence on the temperature distribution of a number of different factors, such as the design of the laser probe, the number of fibres, the optical properties of the tissue, the duration of irradiation, blood perfusion and boundary conditions. New results concerning transurethral microwave thermotherapy were obtained by incorporating the distribution of absorbed microwaves into the model. Prototypes of new laser applicators for anatomically correct treatment of benign prostatic hyperplasia were developed and tested ex vivo. Experimental work on liver tumours pointed to the importance of eliminating the blood flow in the liver during treatment to reduce convective heat loss. In addition, it was shown that hepatic inflow occlusion during treatment increased the thermal sensitivity of tumour tissue. The dynamic influence of interstitial laser thermotherapy on liver perfusion was investigated using interstitial laser Doppler flowmetry. Vessel damage after the combined treatment of laser-induced heat treatment and photodynamic therapy was studied