Radiofrequency Hyperthermia Research Articles

The effects of radiofrequency hyperthermia on pain and function in patients with knee osteoarthritis: a preliminary report

BackgroundThe clinical evidence of the efficacy of hyperthermia on osteoarthritis (OA) has not yet been clearly established. In addition, the application of a modality that can control the temperature inside the joints has not been reported. The purpose of this study was to investigate the effect of percutaneous radiofrequency hyperthermia, which could safely raise the temperature of the body core, in patients with OA knees. MethodsTemperature changes inside the knee joint without OA were measured during exposure to radiofrequency. Radiofrequency hyperthermia was performed on 12 OA knees by exposure to 8 MHz and 200 W for 20 min, 3 times, at 1-week intervals. The clinical outcome was evaluated by use of the Lequesne index (LI) and the Japan Orthopaedic Association (JOA) scale. The osteoarthritis research society international (OARSI) responder criteria were also analyzed. ResultsRadiofrequency hyperthermia of 8 MHz and 200 W for 20 min increased the temperature inside the joint from 34.4 to 39.4°C. The LI decreased by 3.55 points from baseline during the 3 weeks. The JOA scale improved significantly during the period, reaching 86.25 points at the final examination from baseline of 67.5 points. 67% of patients had a response to the therapy according to OARSI criteria. No side effects were observed. ConclusionsRadiofrequency hyperthermia can safely increase the temperature inside the knee joint. Radiofrequency hyperthermia on OA knees provides a remarkable pain relief effect and can improve the patients' daily life. In the future, clinical studies should be performed with a protocol containing more cases, with appropriate control groups.

Prospects for radiofrequency hyperthermia applicator research. I – Pre-optimised prototypes of endocavitary applicators with matching interfaces for prostate hyperplasia and cancer treatments

Inconsistency is observed in comparing assessment data of applicators for endocavitary hyperthermia (EHT) with microwaves (MW) and radiofrequency (RF) obtained using the standard method of inserting bare applicators in phantom tissues. MW antennae exhibit overall average penetration depths of approximately 6 mm, excluding hot spots. RF radiators exhibit penetration depths of not more than approximately 3 mm, a value too low considering the superior penetration of the RF plane wave radiation. Assuming that a mismatch at the RF radiator–tissue interface is causing the poor energy transfer of RF energy, we developed new RF radiators with controlled dielectric matching interfaces for evaluating the potential of RF radiation in EHT and in interstitial hyperthermia (IHT) treatments. We designed, developed and assessed 27.12 MHz, 8 mm OD inductive and capacitive devices of novel and existing designs, each provided an optimised bi-layer matching interface. The assessment results reveal features such as customisable length and shape, independence of insertion depth, uncritical air gap, longitudinal heating uniformity, outstanding penetration depths (19–20 mm) and high SAR gradients at both radiator ends – i.e. prostatic urethra ends – for added safety. These data clear the way for the development of pre-optimised EHT inductive and capacitive RF applicators. Evidence of positive effects of high near-fields density in cavity microenvironments is given. Such devices show potential for more effective prostatic hyperplasia treatments and for improving the feasibility of more adequate treatment planning and thermal dosimetry of interstitial and transurethral hyperthermia treatments of prostate carcinoma.

Feasibility study of high-temperature thermoseed inductive hyperthermia in melanoma treatment

Current treatment modalities for melanoma do not offer satisfactory efficacy. We have developed a new, minimally invasive hyperthermia technology based on radio-frequency hyperthermia. Herein, we investigated the feasibility of using a nickel-copper thermoseed for inductive hyperthermia at a relatively high temperature (46-55 ˚C). In vitro, the thermoseed showed good thermal effects and effective killing of B16/F10 melanoma cells. Temperatures of 53.1 ± 0.5 ˚C were achieved for a single thermoseed and 56.5 ± 0.5 ˚C for two in parallel (spacing 5 mm). No B16/F10 melanoma cells survived with heating time longer than 20 min in the parallel thermoseed group. Magnetic fields or thermoseeds alone did not affect the survival rate of B16/F10 cells (P>0.05). In vivo, B16/F10 melanoma cells were subcutaneously injected into the right axilla of C57BL/6 mice. After the tumors grew to ~11-13 mm, two thermoseeds (spacing 5 mm) were implanted into the tumors and the mice were subjected to an alternating magnetic field (100-250 kHz, 15 kA/m) to induce hyperthermia. The temperature at the center of the tumor reached 46 ˚C at 5 min and plateaued at 50 ˚C. Thermoseed treatment produced large necrotic areas, inhibited tumor growth in 60% (6 of 10) of animals and prolonged survival time (P<0.05). Thus, with further optimization and testing, high-temperature thermoseed inductive hyperthermia may have therapeutic potential for melanoma.

The regimen of gemcitabine and cisplatin combined with radio frequency hyperthermia for advanced non-small cell lung cancer: A phase II study

Purpose: This phase II randomised trial was designed to evaluate the therapeutic efficacy and feasibility of radio frequency regional hyperthermia in combination with chemotherapy for patients with advanced non-small lung cancer (NSCLC).Methods: Eighty patients with pathologically proven advanced NSCLC, were enrolled and divided into two groups. Group A patients were treated by radio frequency regional hyperthermia in combination with the regimen of gemcitabine and cisplatin (GP). Group B patients were treated with the GP regimen alone.Results: In group A, one patient achieved a complete response (CR), 18 achieved a partial response (PR), 18 achieved a stable disease and three experienced a progression of the disease. Thirty-three patients had a positive Clinical Benefit Response (CBR). In group B, no patient achieved CR, 17 achieved PR, 19 achieved a stable disease and four experienced a progression of the disease. Nineteen patients had a positive CBR. Significant differences between the two groups were observed for the CBR (P < 0.05), but not for RR. Major toxicities included bone marrow depression, nausea, vomiting, without significant differences between the two groups (P > 0.05).Conclusions: Radio-frequency regional hyperthermia in combination with chemotherapy (GP) is a safe, well tolerated, and effective therapeutic modality for patients with advanced NSCLC. The addition of hyperthermia improved quality of life.

Controlled radio-frequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by 1H, 23Na and 31P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma

A magnetic resonance (MR) technique is developed to produce controlled radio-frequency (RF) hyperthermia (HT) in subcutaneously-implanted 9L-gliosarcoma in Fisher rats using an MR scanner and its components; the scanner is also simultaneously used to monitor the tumour temperature and the metabolic response of the tumour to the therapy. The method uses the 1H chemical shift of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (TmDOTA−) to monitor temperature. The desired HT temperature is achieved and maintained using a feedback loop mechanism that uses a proportional-integral-derivative controller. The RF HT technique was able to heat the tumour from 33° to 45°C in ∼10 min and was able to maintain the tumour temperature within ±0.2°C of the target temperature (45°C). Simultaneous monitoring of the metabolic changes with RF HT showed increases in total tissue and intracellular Na+ as measured by single-quantum and triple-quantum filtered 23Na MR spectroscopy (MRS), respectively, and decreases in intra- and extracellular pH and cellular bioenergetics as measured by 31P MRS. Monitoring of metabolic response in addition to the tumour temperature measurements may serve as a more reliable and early indicator of therapy response. In addition, such measurements during HT treatment will enhance our understanding of the tumour response mechanisms during HT, which may prove valuable in designing methods to improve therapeutic efficiency.

Local Radiofrequency Hyperthermia Inhibits the Growth of Primary Tumors and Lung Metastases in a 4T1/luc Murine Breast Cancer Model

Radiofrequency hyperthermia has been widely and successfully used for treatment of malignant tumors. Metastatic tumors are suppressed in some patients harboring malignant tumors during primary tumor treatment with hyperthermia. In the present study, regression of tumor size and visceral metastases were investigated in a mouse model involving treatment with local radiofrequency hyperthermia. 4T1/luc murine breast cancer cells were subcutaneously transplanted into the left thighs of female BALB/c mice. When the primary tumors reached a mean diameter of 5 mm, the tumors were treated with local 8 MHz radiofrequency hyperthermia two times a week for 3 weeks ; control animals were not treated with hyperthermia. In another group of mice, primary tumors were treated with doxorubicin injected into the tumor on day 7 after the tumor transplant, and were not treated with radiofrequency hyperthermia. The diameters of the primary tumors, the number of microscopic visceral metastasic foci, and luciferase activity in viscera were measured, and the results were compared between the groups of animals. Splenic lymphocytes were also examined using flow cytometry. Primary tumor growth was suppressed by both local radiofrequency hyperthermia and by intratumoral doxorubicin injection. However, lung metastases were inhibited only by local radiofrequency hyperthermia as shown by microscopic evaluation and luciferase activity assays. Liver metastases were not detected in any mice. The overall survival time was prolonged by local radiofrequency hyperthermia. The number of natural killer cells in the spleen was significantly increased after treatment with local radiofrequency hyperthermia, and this increase in natural killer cells in the spleen might account for the inhibition of lung metastases. In conclusion, primary tumor growth and the frequency of lung metastases were reduced by local radiofrequency hyperthermia treatments in the 4T1/luc mouse model.

Marked Response to Radio-frequency Hyperthermia in a Patient Having Back Pain with No Evidence of Magnetic Resonance Imaging Abnormalities

The patient was a 63-year-old man who had back pain with no evidence of magnetic resonance imaging (MRI) abnormalities. He had never suffered from cancer. When 50-55 min radio-frequency hyperthermia sessions were administered every other day, the pain showed gradual alleviation as heat was applied. By the end of the 4th session, the pain had completely disappeared. The effect persisted for 5 months.

Proposing magnetic nanoparticle hyperthermia in low‐field MRI

AbstractThis work examines feasibility, practical advantages, and disadvantages of a combined MRI/magnetic particle hyperthermia (MPH) system for cancerous tumor treatment in low perfusion tissue. Although combined MRI/hyperthermia systems have been proposed and constructed, the current proposal differs because the hyperthermia system would be specifically designed to interact with the magnetic nanoparticles injected at the tumor site. The proposal exploits the physical similarities between the magnetic nanoparticles currently employed for MPH and those used as superparamagnetic iron oxide (SPIO) contrast agents in MR imaging. The proposal involves the addition of a rotating magnetic field RF hyperthermia source perpendicular to the MRI B0 field which operates in a similar manner to the MRI RF excitation field, B1, but at significantly higher frequency and field strength such that the magnetic nanoparticles are forced to rotate in its presence. This rotation is the source of increases in temperature which are of therapeutic benefit in cancer therapy. For rotating magnetic fields with amplitudes much smaller than B0, the nanoparticles' suspension magnetization rapidly saturates with increasing B0. Therefore, the proposal is best suited to low‐field MRI systems when magnetic saturation is incomplete. In addition, careful design of the RF hyperthermia source is required to ensure no physical or RF interference with the B1 field used for MRI excitation. Notwithstanding these caveats, the authors have shown that localized steady‐state temperature rises in small spherical tumors of up to 10°C are conceivable with careful selection of the nanoparticle radius and concentration, RF hyperthermia field amplitude and frequency. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 36–47, 2010.

51. Nanoparticle enhanced hybrid cryosurgery and RF hyperthermia

51. Nanoparticle enhanced hybrid cryosurgery and RF hyperthermia

Clinical research of intraperitoneal ehemohyperthermia with NRL-002 double RF tumor hyperthermia system on recurrent ovarian cancer

Objective To study the efficacy of intraperitoneal chemohyperthermia with Double RF Tumor Hyperthermia System on recurrent ovarian cancer. Methods 22 cases of advanced recurrent ovarian cancer were infused with hot NS and DDP and VP16 in abdominal cavity, NRL-002 double RF Tumor Hyportherrnia System was applied to heat the abdominal part for 60-120 minutes. RF hyperthermia was given twice per week and chemotherapy once per week. Results The overall response rate (CR+PR) was 63.6%. The serum CA125 ratio was decreased significantly. The level of CD4/CD5 and NK cells was higher than that of pretherapy after management. The clinical beneficial response(CBR) was 81.8%. The median TIP and MST were 7.8 mouth and 18.5 month. Conclusion Intraperitoneal ehemohyporthermia with NRL-002 Double RF Tumor Hyperthermia System was an effective way to treat advanced recurrent ovarian cancer. It Can also improve life quality of patients with mild adverse effect and recommended to be applied clinically. Key words: Ovarian neoplasms; Neoplasms recurrence, local; Intraperitoneal hyperthermo chemotherapy; Prognosis

An RF hyperthermia electrode which generates no edge effect

e22229 Background: For local hyperthermia cancer therapy, radio frequency (RF) capacitive heating with a pair of electrodes is one of the most effective methods. RF hyperthermia with a conventional 2-dimensional square plate electrode produces an ‘edge effect‘ - the focusing of the RF current resulting in focal overheating. We designed and propose a novel hemispherical-shaped RF capacitive heating electrode that generates no edge effect. Methods: A CAD simulation (COMSOL Multiphysics 3.4) was done, and current and specific absorbance ratio (SAR) distributions of both the hemispherical and the conventional square plate shape electrodes were obtained by a 3-D finite element method. Results: The hemispherical electrode generated no focusing of current distribution, nor overheating with SAR elevation, while the square plate electrode produced an edge effect with local SAR elevation. Conclusions: The hemispherical electrode showed no edge effect from focal overheating. Our new electrode may be useful for local heating in the oral or vaginal cavity in clinical use. Phantom studies with a prototype electrode should be carried out for further confirmation. No significant financial relationships to disclose.

Simulation studies promote technological development of radiofrequency phased array hyperthermia

A treatment planning program package for radiofrequency hyperthermia has been developed. It consists of software modules for processing three-dimensional computerized tomography (CT) data sets, manual segmentation, generation of tetrahedral grids, numerical calculation and optimisation of three-dimensional Ε field distributions using a volume surface integral equation algorithm as well as temperature distributions using an adaptive multilevel finite-elements code, and graphical tools for simultaneous representation of CT data and simulation results. Heat treatments are limited by hot spots in healthy tissues caused by Ε field maxima at electrical interfaces (bone/muscle). In order to reduce or avoid hot spots suitable objective functions are derived from power deposition patterns and temperature distributions, and are utilised to optimise antenna parameters (phases, amplitudes). The simulation and optimisation tools have been applied to estimate the improvements that could be reached by upgrades of the clinically used SIGMA-60 applicator (consisting of a single ring of four antenna pairs). The investigated upgrades are increased number of antennas and channels (triple-ring of 3 × 8 antennas and variation of antenna inclination. Significant improvement of index temperatures (1–2°C) is achieved by upgrading the single ring to a triple ring with free phase selection for every antenna or antenna pair. Antenna amplitudes and inclinations proved as less important parameters.

Ultrasound hyperthermia control system for deep-seated tumours: Ex vivo study of excised tumours, modeling of thermal profile and future nanoengineering aspects

Hyperthermia is a technique of raising the temperature locally to treat say tumours. There are several hyperthermia modalities like radio frequency (RF), microwave, and ultrasound. RF and microwave hyperthermia are good for superficial treatment while ultrasound is good for the therapeutic treatment of deep-seated tumours, with the ability of easy focussing. Focussed ultrasound system developed for deep-seated tumours, say in the complex brain tissue, is studied here. Nanotechnological approach is presented here for different control mechanisms for the control of ultrasound intensity, focussing beam, thermal profile of temperature distribution in the tissue and dosage control levels. Ex vivo study of excised tumours, like breast tumours, bone tumours and other such samples, with the present system is also presented. Physical and biological effects on the human health are discussed.

Prospective phase II trial for recurrent high-grade gliomas with capacitive coupled low radiofrequency (LRF) hyperthermia

2047 Background: In spite of many new approaches the treatment of malignant gliomas is still disappointing. Concomitant radiotherapy with temozolomide could improve in a RCT median survival of pts with glioblastoma multiforme from 12.1 to 14.6 months (EORTC 26981- 22981; NCIC,3; ASCO 2004). About 20% of pts with gliomas benefit from therapy depending on genomic mutations. Deep hyperthermia with low radiofrequency capacitive coupled electrodes (LRF-DHT) at 13.56 MHz is feasible in treating pts with brain tumors (Hager ED et al., ASCO 2003,#470). 4/5 of the effective LRF-energy can induce selectively apoptosis in cancer cells instead of heat. Heat alone would be contraindicated for the treatment of tumors in the brain. Therefore, electro-hyperthermia (EHT) is also referred to this technique. Methods: N=179 pts with highly- malignant gliomas (WHO grade III/IV at recurrence or progression) where treated with LRF-DHT after recurrence and/or progression after first-line therapy of the disease after surgery, radiotherapy and/or chemotherapy. N= 53 pts in the astrocytoma WHO grade III group and N=126 pts in the WHO grade IV group (glioblastoma multiforme), KI >50%, where analyzed in an intention-to-treat observational study. Enrollment time was from 02/2000 to 04/2007. Results: Complete data where collected from all pts and considered for evaluation if at least 1 cycle of LRF-DHT could be performed. The median overall survival times (MST) are listed in table 1. Longstanding complete and partial remissions could be achieved after recurrence in both groups. Conclusions: LRF-DHT is feasible in treating pts with highly malignant gliomas without any severe side effects. Hyperthermia with capacitive coupled electrodes may increase overall median survival time (MST) by about 6 months after recurrence and/or progression after first-line therapy. Quality of life and survival could be improved by this method. Further trials are urgently warranted. MST of patients with WHO grade III and IV gliomas (Kaplan-Meier Estimation) MST from Grade III; N =: 53 pts months±se [95%CI] Grade IV; N = 126 pts months±se [95%CI] 1st Diagnosis of Disease 37.0±3.7 [29.8; 44.2] 19.0±1.6 [15.9; 22.1] 1st LRF- Hyperthermia 10.0±1.9 [6.3; 13.7] 7.0±0.8 [5.4; 8.6] Censored N (%) 25 (19.8%) 14 (26.4%) No significant financial relationships to disclose.

A pilot study of weekly docetaxel chemotherapy combined with regional hyperthermia for pretreated stage III non-small cell lung cancer

Objective To evaluate the feasibility and therapeutic effect of chemotherapy combined with regional radio frequency hyperthermia for pretreated locally advanced non-small cell lung cancer.

Docetaxel weekly regimen in conjunction with RF hyperthermia for pretreated locally advanced non-small cell lung cancer: a preliminary study

BackgroundTo evaluate the feasibility and therapeutic effect of chemotherapy combined with regional radio frequency hyperthermia for pretreated locally advanced non-small cell lung cancer.Methods29 patients with stage III non-small cell lung cancer were enrolled in present study, received chemotherapy up to 4 cycles and radio frequency hyperthermia up to 32 times. The primary end points were grade 3,4 hematological or non-hematological toxicities and progression free survival, the secondary end points were response rate, tumor control rate and overall survival. Method of Kaplan-Meier was used for the survival analysis.Results21 patients completed their arranged treatments. The most common grade 3,4 toxicity was neutropenia (24.1%). Median progression free survival was 4 months (range 0–13 months), one year progression free survival rate was 10.3%. Overall response rate was 25.9%, tumor control rate was 66.6%. Median overall survival was 11 months (range 2–18+ months), one year overall survival rate was 44.8%.ConclusionTreatment of chemotherapy in conjunction with regional hyperthermia was safe and well tolerant, it suggested an impressive tumor control rate and an acceptable one year progression free survival. Further study might be needed.

Nursing experience of radiofrequency hyperthermia for the treatment of malignant tumor patients

目的 总结恶性肿瘤患者行射频热疗的护理经验.方法 回顾性分析600例患者接受射频热疗时的常见并发症,制定治疗前、中、后护理措施.结果 600例患者均安全完成治疗,发生皮下脂肪过热仅50例,皮肤过热仅20例.结论 使用射频热疗治疗恶性肿瘤是一种安全且损伤小、副反应较少的治疗方法,治疗前、中、后实施合理的护理是保证治疗成功的重要环节。

Chest-Wall Metastasis in a Patient who Underwent Liver Transplantation Due to Hepatocellular Carcinoma

Hepatocellular carcinoma is a common malignancy. It may cause extrahepatic metastases through haematogenous or lymphatic dissemination or direct invasion. Furthermore, methods such as fine-needle aspiration biopsies performed to obtain a diagnosis or percutaneous ethanol injection and radiofrequency hyperthermia performed for treatment may also cause tumour dissemination. We present a 52-year-old male patient whose isolated right chest wall metastasis developed after liver transplantation due to hepatocellular carcinoma. We performed chest wall reconstruction after the mass was removed.

Radiofrequency hyperthermia in combination with internvention chemotherapy in the treatment of advanced colorectal cancer

目的 观察射频热疗联合介入持续动脉化疗治疗晚期大肠癌的临床初步疗效.方法 对20例局部复发和伴有肝、肺、骨、腹腔、盆腔及腹股沟淋巴结转移的晚期大肠癌患者经射频热疗法联合供养靶动脉介入灌注化疗.每例患者至少进行2个周期的介入化疗联合热疗.化疗方案为第1～3天亚叶酸钙200 mg/m2静脉滴注;第1天顺氯氨铂80 mg/m2,第1～3天如肾功能改变则改用鬼臼乙叉苷60 mg/m2动脉滴注;5-氟尿嘧啶2 500 mg/m2加入超液化碘油10～30 ml中进行肝动脉灌注栓塞.热疗频率40.68 MHz,电容式加热,电极直径20～25 cm,入射功率500～800 W,反射功率20～40 W.插管化疗第2天开始进行热疗,每72小时1次,每次50～70 min,每疗程化疗配合4～8次热疗.结果 病灶近期疗效以CT或B超检查结果作为评价标准,完全缓解0例,部分缓解14例,总有效率为70.0%.患者化疗未出现严重不良反应.热疗不良反应为局部疼痛和脂肪硬结,不需特殊处理.结论 射频热疗联合介入持续动脉化疗治疗晚期大肠癌安全、有效。

0621: A Radiofrequency Hyperthermia Assisted Hdr Brachytherapy in Recurrent Endometrial and Cervical Cancer Treatment in Previously Irradiated Field

0621: A Radiofrequency Hyperthermia Assisted Hdr Brachytherapy in Recurrent Endometrial and Cervical Cancer Treatment in Previously Irradiated Field