Most patients treated with hyperthermia have tumors which are refractory advanced and/or recurrent tumors which cannot be controlled by conventional treatments, and their performance status is often poor. Thus, it is very difficult for these patients to maintain a physical position suitable for heating tumors whose temperatures can be maintained at more than 42°C for nearly an hour (in order to induce direct toxicity in tumor cells). Furthermore, we sometimes cannot help interrupting the heating due to acute adverse reactions such as severe pain. In addition, it is also very difficult to heat tumors homogeneously to temperatures over 42°C, using currently available heating devices. In many clinical studies in which hyperthermia was used to enhance the efficacy of radiotherapy, tumor temperatures could be increased only to the 40-41.5°C range. Under these conditions, heat-induced cell death, increased cellular radiosensitivity, and vascular damage are likely to be insignificant in spite of the increased response of tumors to radiotherapy. Recently, mild temperature hyperthermia (MTH)-induced physiological effects on tumors have been shown to lead to an increased blood flow and a resulting increase in tumor oxygenation, and this could lead to increased radiosensitivity if radiotherapy was used after MTH, and to an increase in chemosensitivity via an increased transport of drugs into tumors. Therefore, if the clinician's goal is to keep the tumor temperature in the 40-41°C range, it is possible to reduce a patient's burden, make it easier to maintain a patient in a suitable position for heating, and avoid interrupting the heating session. In thermoradiotherapy, when heating at temperatures higher than 42-43°C can be warranted, hyperthermia should be performed after radiotherapy. However, when heating over 42°C is difficult, an alternative useful approach may be to reverse the order of radiotherapy and hyperthermia : specifically apply radiotherapy subsequent to tumor oxygenation-inducing MTH.

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Interest in molecular imaging and in molecularly-targeted therapy has grown tremendously, and ultrasound may offer new tools for modern cancer therapy. To understand how therapeutic ultrasound works, it is necessary to understand its biological effects at the molecular level. In this review, investigations on the molecular aspects of ultrasound are discussed, with emphasis on apoptosis induction, gene expression, and gene transfection. In these studies, apoptosis induction was assayed with flow cytometry and with other methods targeting indicators of apoptosis. Gene expression was evaluated using western blotting, real-time polymerase chain reaction, and microarray analysis. Gene transfection was investigated using a luciferase assay and other methods. The reported results show that low intensity ultrasound can induce apoptosis in cancer cell lines, and that this effect can be optimized using pulsed ultrasound. Exposure to ultrasound can result in the down-regulation or up-regulation of some genes. Of particular interest is the striking up-regulation of the heme oxygenase-1 gene, a gene usually associated with oxidative stress in human lymphoma U937 cells. Introducing genes using ultrasound with or without microbubbles also exhibited promising results. Membrane damage is pivotal to biological effects, and using ultrasound to modify or affect cell membranes can either promote or inhibit desired effects. In summary, it is concluded that ultrasound has the potential to help develop useful methods which can be utilized in therapies which require apoptosis induction, gene introduction into cells, alterations in gene regulation, and drug-activation.

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Thermal ablation can be achieved using microwave coagulation therapy (MCT) and radiofrequency ablation (RFA), and has been developed as a curative and minimally invasive treatment for hepatocellular carcinoma (HCC). A percutaneous, endoscopic, or open body approach can be selected based on the size, number, and location of the tumors. MCT is achieved with monopolar-type electrodes to create a columnar ablative area with a 1 cm diameter centered around the electrode. RFA is achieved with internally cooled electrodes (Cool-tip^TM) or expandable electrodes (LeVeen^TM and RITA^TM). RFA can produce a spheroidal ablative area with a 3 cm diameter surrounding the needle. Three- and 5- year overall survival rates are 80.0-81.0% and 43.0-78.0% for MCT, and 62.0-77.7% and 33.3-55.4% for RFA, respectively. Morbidity and mortality rates using thermal ablation are 2.2-8.9% and 0.3-0.5%, respectively. Thermal ablation, using MCT or RFA, can provide a favorable long-term prognosis with low morbidity rates for HCC patients with poor liver function reserves.

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A new heating technique is proposed for deep heating using an annular-shaped Inductive Aperture-Type Applicator (IATA). It was shown using finite element analysis that this heating technique could concentrate RF energy in the central or core portion of the human body to generate heat without causing excessive heating of the outer or fat layers.
A fat-muscle cylindrical phantom with a diameter of 0.30 m was inserted into the opening of an annular-shaped IATA, which has an outer diameter of either 0.74 or 0.94 m, a height of 0.20 or 0.30 m, and an opening 0.34 m in diameter, and is excited by RF currents of 13.56 or 27.12 MHz. The heat generated in the central portion of the phantom was 1.11-1.27 times that of the maximum value in the peripheral muscle portion of the phantom, while heat generated in the fat layer was only 20% of that generated in the central portion of the phantom.

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This case report describes a 40 year old man with a fibrosarcoma arising from the left lower extremity. The tumor was seated deeply in the left lower extremity and the tumor size was 13 cm in diameter and 24 cm in length. The patient was treated with a preoperative combination of hyperthermia and radiotherapy followed by a limb-sparing surgical resection. Radiation therapy was delivered using a Linac 6-MV Xray with two opposed beams. The dose was 3 gray (Gy) per fraction, 5 times per week, for a total dose of 30 Gy. Hyperthermia was given twice a week, and started within 15 minutes after irradiation. Hyperthermia was performed using a Thermotron RF-8, and applied for approximately 40 minutes to achieve a temperature of over 42°C in the tumor. Limb-sparing surgical resection was performed eight days after the completion of radiotherapy and hyperthermia. No local recurrence was observed after 67 months. Furthermore, no serious complications were observed after surgery, and the function of the limb has been completely preserved.
A combination of preoperative thermoradiotherapy and marginal resection for fibrosarcomas arising in the lower extremities may offer a useful therapy for preserving function and for local control. This report describes a fibrosarcoma case arising from a lower extremity which was successfully treated by thermoradiotherapy and limb-sparing surgical resection.

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