Hyperthermia In Oncology Research Articles

Heating efficiency of agarose samples doped with magnetic nanoparticles subjected to ultrasonic and magnetic field

Recently, magneto-ultrasound heating of tissue in the presence of magnetic nanoparticles (NPs) has been studied due to its high potential for use in oncological hyperthermia. It has been published that a synergistic effect, generation of additional heat caused by magneto-ultrasonic coupling, was observed in a tissue-mimicking material (TMM) enriched with magnetic NPs. The specific absorption rate (SAR) was determined from the temperature rise measurements in a focus of the ultrasound beam. It is important to use precise measurement methods when considering medical applications, for which there are limitations to the power of each field, resulting from the prevention of biological phenomena dangerous to the patient. This study demonstrates that in magneto-ultrasonic heating SAR can be measured much more accurately if the ultrasonic field is almost uniform. Measurements were performed on TMM containing Fe3O4 NPs with a diameter of approximately 8 nm and superparamagnetic properties. Both, the measurement and simulation results showed that the errors resulting from the inaccuracy of placing the temperature probe are smaller than in the case of the focused ultrasound. At the same time, the temperature increase caused by the ultrasonic field is almost linear and the influence of heat convection on the SAR determination is negligible. The measurements showed that magneto-ultrasonic hyperthermia can provide the desired thermal effect at lower ultrasound powers and magnetic fields compared to ultrasonic or magnetic hyperthermia used alone. No synergy effect was recorded.

Oncological Hyperthermia: Where to Go from Here?

Oncological Hyperthermia: Where to Go from Here?

Oncological Hyperthermia and Quality of Life

Oncological Hyperthermia and Quality of Life

Systematic review of the registered clinical trials for oncological hyperthermia treatment

Background The use of heat to treat various diseases is called hyperthermia treatment (HT). Since the 1970s, the anti-cancer effects of HT have been investigated. Different HT techniques can be categorized as local, regional and whole-body hyperthermia treatment (WBHT). We aim to provide a summary of recent research done on HT to treat cancer. Methods In July 2020 ClinicalTrials.gov were systematically searched for all trials including hyperthermia and cancer registered between 2000 and 2020. Studies were excluded when they did not concern hyperthermal treatment, when they were not oncological studies, when they were observational or other non-interventional studies. Results Of 1654 identified trials, 235 were included. Of these 235 studies, 123 described the use of HIPEC (52.3%), 44 other types of regional HT (18.7%), 45 local HT (19.1%) and 15 WBHT (6.4%). A steady increase (720%) in research to hyperthermic intraperitoneal chemotherapy (HIPEC) can be observed in the last decade. Although HIPEC is the most researched HT modality, an evolution in other HT technologies could be observed during the past decade. Conclusions Research to HT to treat cancer has expanded fast. Some techniques, for example HIPEC start to be used outside of research context, but overall, more research is needed to establish a clear effect of these HT techniques.

Design and Characterization of an RF Applicator for In Vitro Tests of Electromagnetic Hyperthermia.

The evaluation of the biological effects of therapeutic hyperthermia in oncology and the precise quantification of thermal dose, when heating is coupled with radiotherapy or chemotherapy, are active fields of research. The reliable measurement of hyperthermia effects on cells and tissues requires a strong control of the delivered power and of the induced temperature rise. To this aim, we have developed a radiofrequency (RF) electromagnetic applicator operating at 434 MHz, specifically engineered for in vitro tests on 3D cell cultures. The applicator has been designed with the aid of an extensive modelling analysis, which combines electromagnetic and thermal simulations. The heating performance of the built prototype has been validated by means of temperature measurements carried out on tissue-mimicking phantoms and aimed at monitoring both spatial and temporal temperature variations. The experimental results demonstrate the capability of the RF applicator to produce a well-focused heating, with the possibility of modulating the duration of the heating transient and controlling the temperature rise in a specific target region, by simply tuning the effectively supplied power.

Thermosensitive Polymers and Thermo-Responsive Liposomal Drug Delivery Systems.

Temperature excursions within a biological milieu can be effectively used to induce drug release from thermosensitive drug-encapsulating nanoparticles. Oncological hyperthermia is of particular interest, as it is proven to synergistically act to arrest tumor growth when combined with optimally-designed smart drug delivery systems (DDSs). Thermoresponsive DDSs aid in making the drugs more bioavailable, enhance the therapeutic index and pharmacokinetic trends, and provide the spatial placement and temporal delivery of the drug into localized anatomical sites. This paper reviews the fundamentals of thermosensitive polymers, with a particular focus on thermoresponsive liposomal-based drug delivery systems.

Heterogeneous Heat Absorption Is Complementary to Radiotherapy.

Simple SummaryThis review shows the advantages of heterogeneous heating of selected malignant cells in harmonic synergy with radiotherapy. The main clinical achievement of this complementary therapy is its extreme safety and minimal adverse effects. Combining the two methods opens a bright perspective, transforming the local radiotherapy to the antitumoral impact on the whole body, destroying the distant metastases by “teaching” the immune system about the overall danger of malignancy.(1) Background: Hyperthermia in oncology conventionally seeks the homogeneous heating of the tumor mass. The expected isothermal condition is the basis of the dose calculation in clinical practice. My objective is to study and apply a heterogenic temperature pattern during the heating process and show how it supports radiotherapy. (2) Methods: The targeted tissue’s natural electric and thermal heterogeneity is used for the selective heating of the cancer cells. The amplitude-modulated radiofrequency current focuses the energy absorption on the membrane rafts of the malignant cells. The energy partly “nonthermally” excites and partly heats the absorbing protein complexes. (3) Results: The excitation of the transmembrane proteins induces an extrinsic caspase-dependent apoptotic pathway, while the heat stress promotes the intrinsic caspase-dependent and independent apoptotic signals generated by mitochondria. The molecular changes synergize the method with radiotherapy and promote the abscopal effect. The mild average temperature (39–41 °C) intensifies the blood flow for promoting oxygenation in combination with radiotherapy. The preclinical experiences verify, and the clinical studies validate the method. (4) Conclusions: The heterogenic, molecular targeting has similarities with DNA strand-breaking in radiotherapy. The controlled energy absorption allows using a similar energy dose to radiotherapy (J/kg). The two therapies are synergistically combined.

Effect of synthesis conditions on local atomic structure and properties of low-toxic maghemite nanoparticles for local magnetic hyperthermia in oncology

Effect of synthesis conditions on local atomic structure and properties of low-toxic maghemite nanoparticles for local magnetic hyperthermia in oncology

Review on the Use of Modulated Electro-Hyperthermia as a Stand-Alone Therapy in a Palliative Setting: Potential for Further Research?

Background: Hyperthermia (HT) in oncology was originally applied as a stand-alone treatment (monotherapy), but achieving temperatures required to cause cellular destruction (>43ºC) proved to be challenging. Lower temperatures may increase the risk of dissemination of the treated tumours. Hyperthermia in the current context of oncology therefore aims to achieve moderate temperatures of 39ºC - 41.5ºC and is applied in combination with chemotherapy (ChT) and/or radiotherapy (RT). Modulated electro-hyperthermia (mEHT) applies amplitude modulation to an electric field generated by a capacitive coupled set-up, to selectively heat tumours. As mEHT does not appear to increase the risk of disease dissemination, it has been investigated as a stand-alone treatment for patients with advanced disease and who have exhausted all other treatment options. This report is a descriptive review of papers in oncology which report on the use of mEHT as a stand-alone treatment in a palliative setting. We aim to establish whether there is motivation for the development of trials to further investigate mEHT as a monotherapy in a palliative setting. Methods: A literature search was conducted using the key words “Oncothermia”, “modulated electro-hyperthermia” and “monotherapy”, and case reports were excluded. Only studies which applied mEHT without ChT or RT; for palliative intent; when conventional therapies have failed; or when no further options are available, were included. Results: Six phase I/II studies on tumours of the liver, brain, pancreas, and stomach were included. The studies demonstrated the safety of mEHT; disease stabilisation; and improved quality of life. Conclusion: mEHT may have a role in the palliative management of certain tumours in the absence of any other treatment options. The development of robustly designed studies on mEHT for palliative management of oncology patients is motivated.

Statistical Analysis of Ultrasonic Scattered Echoes Enables the Non-invasive Measurement of Temperature Elevations inside Tumor Tissue during Oncological Hyperthermia

Non-invasive monitoring of temperature elevations inside tumor tissue is imperative for the oncological thermotherapy known as hyperthermia. In the present study, two cancer patients, one with a developing right renal cell carcinoma and the other with pseudomyxoma peritonei, underwent hyperthermia. The two patients were irradiated with radiofrequency current for 40 min during hyperthermia. We report the results of our clinical trial study in which the temperature increases inside the tumor tissues of patients with right renal cell carcinoma and pseudomyxoma peritonei induced by radiofrequency current irradiation for 40 min could be detected by statistical analysis of ultrasonic scattered echoes. The Nakagami shape parameter m varies depending on the temperature of the medium. We calculated the Nakagami shape parameter m by statistical analysis of the ultrasonic echoes scattered from the tumor tissues. The temperature elevations inside the tumor tissues were expressed as increases in brightness on 2-D hot-scale maps of the specific parameter αmod, indicating the absolute values of the percentage changes in m values. In the αmod map for each tumor tissue, the brightness clearly increased with treatment time. In quantitative analysis, the mean values of αmod were calculated. The mean value of αmod for the right renal cell carcinoma increased to 1.35 dB with increasing treatment time, and the mean value of αmod for pseudomyxoma peritonei increased to 1.74 with treatment time. The increase in both αmod brightness and the mean value of αmod implied temperature elevations inside the tumor tissues induced by the radiofrequency current; thus, the acoustic method is promising for monitoring temperature elevations inside tumor tissues during hyperthermia.

The Capacitive Coupling Modalities for Oncological Hyperthermia

The local-regional oncological hyperthermia has various electromagnetic methods for energy-transfer. The differences involve conceptual considerations and technical solutions. The most frequently applied energy transfer is capacitive coupling, concentrating the electric field to be the active heating component. The realization of the capacitive coupling set-up is divided into two different categories based on their goals for heating: 1) the homogeneous (conventional) heating, using isothermal conditions for dosing, and 2) the selective heterogeneous heating, using cellularly absorbed energy for dosing. The homogeneous heating utilizes plane-wave matching, absorbing the wave for energy transfer. The heterogenic heating uses impedance matching, selecting the malignant cells by their electromagnetic specialties, like their heterogenic impedance, higher membrane-raft density, and different spatio-temporal (pathologic pattern) arrangements. This article’s objective is to compare and discuss the details of the two kinds of capacitive coupling techniques.

The Evaluation of Oncological Hyperthermia Centers and Turkey Modeling Oncological Hyperthermia Centers and Turkey Modeling

Introduction and Objectives: The latest technology and current treatments are used in the treatment of cancer in Turkey; however, oncological hyperthermia devices are currently not available. This study aimed to demonstrate the necessity of oncological hyperthermia devices in Turkey where cancer treatment is performed effectively. In this direction, some important oncological hyperthermia centers have been examined to what kind of planning can be developed in this country. Materials and Methods: The data were collected regarding the number of patients who had undergone hyperthermia during the treatment of cancer and the distribution of oncological diagnoses, devices per population, and rate of hyperthermia use. Subsequently, a model was prepared for Turkey, and an evaluation was performed on the number of cancer patients that can be applied to this treatment and the need for the number of oncological hyperthermia devices. Results: According to the data obtained, an average of 375 patients are treated annually per hyperthermia device in relevant centers. When a similar projection is applied for Turkey, hyperthermia treatment can be applied to an average of 400 patients annually with 0.18 hyperthermia devices per one million population. According to this result, considering the population and the annual cancer diagnosis rates, it is predicted that 13 deep regional hyperthermia devices are required across the country. Conclusion: The presence of deep regional hyperthermia devices in comprehensive oncology centers plays an effective role in oncological treatment with modern radiotherapy devices. This condition along with the sufficient number of radiation oncologists will significantly benefit the capacity to provide oncological treatment options holistically.

Modulated Electrohyperthermia: A New Hope for Cancer Patients.

According to the World Health Organization, the prevalence of cancer has increased worldwide. Oncological hyperthermia is a group of methods that overheat the malignant tissues locally or systematically. Nevertheless, hyperthermia is not widely accepted, primarily because of the lack of selectivity for cancer cells and because the temperature-triggered higher blood flow increases the nutrient supply to the tumor, raising the risk of metastases. These problems with classical hyperthermia led to the development of modulated electrohyperthermia (mEHT). The biophysical differences of the cancer cells and their healthy hosts allow for selective energy absorption on the membrane rafts of the plasma membrane of the tumor cells, triggering immunogenic cell death. Currently, this method is used in only 34 countries. The effectiveness of conventional oncotherapies increases when it is applied in combination with mEHT. In silico, in vitro, and in vivo preclinical research studies have all shown the extraordinary ability of mEHT to kill malignant cells. Clinical applications have improved the quality of life and the survival of patients. For these reasons, many other research studies are presently in progress worldwide. Thus, the objective of this review is to highlight the capabilities and advantages of mEHT and provide new hopes for cancer patients worldwide.

Quo Vadis Oncological Hyperthermia (2020)?

Heating as a medical intervention in cancer treatment is an ancient approach, but effective deep heating techniques are lacking in modern practice. The use of electromagnetic interactions has enabled the development of more reliable local-regional hyperthermia (LRHT) techniques whole-body hyperthermia (WBH) techniques. Contrary to the relatively simple physical-physiological concepts behind hyperthermia, its development was not steady, and it has gone through periods of failures and renewals with mixed views on the benefits of heating seen in the medical community over the decades. In this review we study in detail the various techniques currently available and describe challenges and trends of oncological hyperthermia from a new perspective. Our aim is to describe what we believe to be a new and effective approach to oncologic hyperthermia, and a change in the paradigm of dosing. Physiological limits restrict the application of WBH which has moved toward the mild temperature range, targeting immune support. LRHT does not have a temperature limit in the tumor (which can be burned out in extreme conditions) but a trend has started toward milder temperatures with immune-oriented goals, developing toward immune modulation, and especially toward tumor-specific immune reactions by which LRHT seeks to target the malignancy systemically. The emerging research of bystander and abscopal effects, in both laboratory investigations and clinical applications, has been intensified. Our present review summarizes the methods and results, and discusses the trends of hyperthermia in oncology.

Temperature elevation in tissue detected in vivo based on statistical analysis of ultrasonic scattered echoes

It is demanded to monitor temperature in tissue during oncological hyperthermia therapy. In the present study, we non-invasively measured the temperature elevation inside the abdominal cavity and tumour tissue of a living rat induced by capacitive-coupled radiofrequency heating. In the analysis of ultrasound scattered echoes, the Nakagami shape parameter m in each region of interest was estimated at each temperature. The Nakagami shape parameter m has temperature dependence; hence, the temperature increase inside tissue specimens can be detected with the m values. By carrying out in vivo experiments, we visualized the temperature increase inside the abdominal cavity and tumour tissue of living rats using two-dimensional hot-scale images indicating the absolute values of the ratio changes of the m values. In both the abdominal cavity and tumour tissue, the brightness in the hot-scale images clearly increased with increasing temperature. The increases in brightness in the hot-scale images imply the temperature elevations inside the abdominal cavity and tumour tissue of the living rats. The study results prove that the acoustic method we proposed is a promising method for monitoring changes in the internal temperature of the human body under hyperthermia treatment.

Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System.

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

Local Atomic and Electronic Structures of Superparamagnetic Nanoparticles Based on Iron Oxides for Local Hyperthermia in Oncology

Iron oxide-based superparamagnetic nanoparticles (Fe3O4) are obtained using the solvothermal synthesis. Both the pure nanoparticles of Fe3O4 and nanoparticles doped by samarium and gadolinium are obtained to manipulate their characteristics. The materials were investigated using X-ray diffraction, X-ray fluorescence, vibrating-sample magnetometry, electron microscopy, electron diffraction, and FT-IR spectroscopy. The nanoparticles have the average size of about 22.3 nm, a crystal lattice of magnetite, and superparamagnetic characteristics at room temperature. Based on the FT-IR spectroscopy, all the synthesized nanoparticles included in their composition a polyethylene glycol coating. The hyperthermic characteristics (SAR and ILP) are determined for the obtained nanoparticles in an alternating magnetic field (AMF). The promising prospects of using the discussed superparamagnetic nanoparticles based on iron oxide particles doped by the atoms of the rare-earth elements for the local magnetic hyperthermia are shown.

Emerging hyperthermia applications for pediatric oncology.

Local application of hyperthermia has a myriad of effects on the tumor microenvironment as well as the host's immune system. Ablative hyperthermia (typically>55°C) has been used both as monotherapy and adjuvant therapy, while mild hyperthermia treatment (39-45°C) demonstrated efficacy as an adjuvant therapy through enhancement of both chemotherapy and radiation therapy. Clinical integration of hyperthermia has especially great potential in pediatric oncology, where current chemotherapy regimens have reached maximum tolerability and the young age of patients implies significant risks of late effects related to therapy. Furthermore, activation of both local and systemic immune response by hyperthermia suggests that hyperthermia treatments could be used to enhance the anticancer effects of immunotherapy. This review summarizes the state of current applications of hyperthermia in pediatric oncology and discusses the use of hyperthermia in the context of other available treatments and promising pre-clinical research.

2E2-3 Non-invasive measurement of temperature elevation inside tumor tissue during oncological hyperthermia treatment by statistical analysis of ultrasonic scattered echoes

2E2-3 Non-invasive measurement of temperature elevation inside tumor tissue during oncological hyperthermia treatment by statistical analysis of ultrasonic scattered echoes

Bioelectromagnetic Paradigm of Cancer Treatment—Modulated Electro-Hyperthermia (mEHT)

One of the most frequently applied bioelectromagnetic effects is the deep heating of the living species with EMF energy. Despite its long history, hyperthermia is a rarely applied oncotherapy. The reason is its controversial results and complicated control. One of the solutions is concentrating the electromagnetic energy nanoscopically on the parts of the malignant cells instead of heating up the complete tumor-mass. This approach is a kind of non-uniform energy absorption, providing energy liberation only in the selected regions. The energy-absorption of the malignant cells targets the membranes and creates a situation far from thermal equilibrium. The selection of the malignant cells is based on their decided differences from their healthy counterparts. The distinguishing parameters are the electromagnetic properties of the components of the malignant tissue which are the physiologic differences between the malignant cells and their healthy counterparts. The targets realize nano-range heating, using natural nanoclusters on the cell-membrane without artificially implementing them. This energy absorption generates consequent reactions, like programmed cell-death (apoptosis) continued by immunogenic cell-death involving extended immune reactions. The applied radiofrequency current is amplitude modulated by time-fractal modulation pattern. The accurately matched impedance realizes the self-selective mechanisms which are promoted by stochastic resonances. This complex method is a new kind of hyperthermia, named mEHT. Our objective is to analyze the problems of the selective, non-equilibrium energy absorption, and present a solution by the electromagnetic mechanisms for an effective and controllable hyperthermia in oncology.