Valentina V. Ostapenko

A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma

To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyper-thermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.

Bax and Bcl-2 protein expression following radiation therapy versus radiation plus thermoradiotherapy in stage IIIB cervical carcinoma

The relative amounts of Bcl‐2 and Bax proteins determine cell survival or death following an apoptotic stimulus. To clarify the molecular mechanism of cell death after radiotherapy or thermoradiotherapy and its relation to the response of AJCC/UICC Stage IIIB cervical carcinomas, the expression of Bax and Bcl‐2 proteins was investigated both before and in the course of treatment given during this study.

Kadota Fund International Forum 2004. Application of thermal stress for the improvement of health, 15-18 June 2004, Awaji Yumebutai International Conference Center, Awaji Island, Hyogo, Japan : Final Report

Japan Health Foundation, Kyoto, Japan, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands, Duke University Medical Center, Durham, USA, AINO Hospital, Osaka, Japan, University of Groningen, Groningen, The Netherlands, Nara Medical University, Nara, Japan, Memorial Sloan Kettering Cancer Center, New York, USA, Inha University, Inchon, Korea, Thomas Jefferson University, Philadelphia, USA, Shouseikai Nishide Hospital, Osaka, Japan, Roswell Park Cancer Institute, Buffalo, USA, Nagasaki University, Nagasaki, Japan, and University of Minnesota, Minneapolis, USA

Increased resistance of the radiosensitive M10 mutant cells of the L5178Y mouse lymphoma cell line to heat-induced apoptosis.

M10 cells, which are deficient in the repair of DNA DSBs and are therefore radiosensitive, are about twofold more thermoresistant than their parental L5178Y cells. We found that, after heat shock at 43 degrees C under conditions resulting in 10% survival (D(10)), M10 cells did not undergo apoptosis, whereas L5178Y cells did undergo apoptosis. M10 cells, but not L5178Y cells, constitutively expressed Hsp72 protein. Moreover, the M10 cells accumulated higher amounts of the heat-inducible form of Hsp72. The patterns of activation of the DNA-binding activity of HSF (heat-shock factor) differed in M10 and L5178Y cells. In response to heat shock, M10 cells accumulated greater amounts of Trp53 protein (formerly known as p53) than the parental cells. Cdkn1a (formerly known as p21, Waf1) was constitutively expressed and further accumulated after heat shock only in M10 cells. We suggest that heat-inducible Hsp72 to a larger extent, and constitutive Hsp72 to a lesser extent, together with Cdkn1a may be involved in the protection of M10 cells against heat-induced apoptosis. Apoptosis in these cells is likely to occur in Trp53-dependent manner.

Relevance of a New Impedance Matching, or Subtrap, Method for the Reduction of Pain During Hyperthermia

Capacitive heating is widely used in hyperthermic treatment of human malignancies. However, the pain on the body surface or thermoesthesia in the subcutaneous fatty layer may prevent an elevation of temperature in the tumors. Impedance matching is improved by a subtrap method entailing the application of two copper plates (10 x 850 x 0.06 mm) as a subtrap circuit to each of two capacitive electrodes. In a clinical trial the Tmax, Tave, Tmin for the subtrap method were all higher in comparison with those for the conventional technique (42.5 +/- 0.7 degrees C, 41.9 +/- 1.0 degrees C, 41.3 +/- 1.1 degrees C vs. 41.1 +/- 1.5 degrees C, 40.6 +/- 1.3 degrees C, 40.0 +/- 1.3 degrees C). Although the maximal radiofrequency (RF) power applied to patients was higher with the subtrap method (875 +/- 189 W vs. 763 +/- 200 W), the incidence of surface pain was reduced dramatically. It is concluded that the subtrap method substantially improves the RF capacitive heating of deep-seated tumors.

Physiology and Psychology in Hyperthermic Oncology: Contribution of Clinical Oncologists in the Development of Heating of Deep-Seated Tumors

Heating deep-seated tumors, which is not an easy task, cannot be solved by physics alone although heating itself is a matter of physics. A deep understanding of human physiology is indispensable, including some psychophysiological aspects. The process of development of a hyperthermia apparatus, the Thermotron RF-8, is analyzed from the standpoints of engineers and clinical oncologists. For a wider use of hyperthermia, further manipulation of physiology such as skin anesthesia and administration of indomethacine would contribute to the improvement of deep-seated tumors as well. When we have a successful system for deep heating, hyperthermia will have a new dimension in its use for suppressing tumor growth as a kind of conservative or alleviating treatment modality.