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The paper presents an analysis of literature on the results of treatment of edematous breast cancer as well as own data on the use of local hyperthermia for this pathology. Local hy- perthermia in combination with chemotherapy (thermochemo- therapy) was applied in 14 patients with secondary edematous breast cancer. Age of patients ranged from 37 to 72 years (mean 53 years). The study results indicate promising applica- tions of thermochemotherapy in edematous breast cancer: for operable patients as neoadjuvant, for inoperable patients as palliative method of treatment.

The study is based on the results of treatment of 60 patients with locally advanced laryngeal cancer (T3-4N0-3M0) exposed to combined treatment: 31 with preoperative chemoradiothera-py, 29 thermochemoradiotherapy. Radiotherapy was performed in the hyperfractionated mode: “1 Gy +1 Gy” (every 4-5 hours) 5 times a week to 30-40 Gy in total. Local hyperthermia was performed 2 times a week before the second fraction of radiotherapy in 3-4 sessions. Eight-day courses of chemotherapy were administered in the beginning of radiotherapy by scheme: vincristine (1. 4 mg/m2 per 1day), cisplatin (20 mg/m2 2, 3, 4 days), bleomycetin (10 mg/m2 5, 6 days), cyclophosphamide (200 mg/m2 7, 8 days). Surgical treatment was performed through 2,5 3 weeks after completion of radiotherapy. Local hyperthermia intensified the course of radiation reaction on the mucous of the larynx but not significant influenced on healing of surgical wounds. Thermochemoradiotherapy compared with chemoradiotherapy raised local relapse-free survival from 75 to 93% (p = 0. 07), regional, for a group of patients with stage N1-3 from 33 to 70%, N1-2 from 40 to 78% (p = 0. 1), loco -regional from 67 to 87% (p = 0. 04). Our findings suggest the necessity for further research on the use of thermochemoradiotherapy in combined treatment of patients with locally advanced laryngeal cancer.

The purpose of the study is to investigate the effectiveness of thermochemotherapy in patients with colorectal cancer metastases to the liver in palliative mode. Loco-regional hyperthermia in combination with chemotherapy was applied to 33 patients. The comparison group was of 40 patients who underwent only chemotherapy. 5-fluorouracil (5-FU) or capecitabine over standard regimens were used for chemotherapy in both groups. Loco-regional hyperthermia was carried out by capacitive method for 40-90 minutes at a maximum temperature within 41-44 ° C in tumor. No significant differences in dynamics of the overall status, clinical symptoms of the disease and biochemical parameters between the groups were revealed. In the group of patients with thermochemotherapy there were received a complete response in 3 patients (9%), partial response - in 14 patients (44%) while in the group of patients with chemotherapy - in 1 patient (3%) and 11 patients (28%), respectively. The significant difference was found in terms of objective response, i.e. summarized parameters of complete and partial regression (p=0.04). Thermochemotherapy compared with chemotherapy significantly increased survival rates of patients.

The combined treatment with preoperative chemoradiotherapy (CRT) was performed in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) was carried out according to the scheme "1 + 1 Gy" (interval 4-5 hours) 5 times a week till 30-40 Gy. RT was accompanied by simultaneous polychemotherapy: vincristine (1.4 mg/m² per day), cisplatin (20 mg/m²--2-4 days) bleomicetin (10 mg/ m²--5, 6 days), cyclophosphamide (200 mg/m²--7, 8 days). Surgical treatment was carried out in 2.5-3 weeks after CRT. CRT allowed conducting organ-saving surgery on the larynx in 11 (52%) of 21 patients with T3 of primary tumor. All other patients underwent laryngectomy at a different volume. Five-year disease-free survival for the whole group in total (T3-4) was 88%. Relapses of regional metastases (MTS) occurred in 7 of 9 patients including in 4 of 5 patients after lymphadenectomy. The overall survival of patients with T3N02 was 71%, with T4N0-3--20%. Thus we have developed a method of treatment allowing to achieve high local relapse-free survival in patients with locally advanced laryngeal cancer. However organ-saving effectiveness of preoperative CRT and its effect on regional MTS remain low, which requires further research in this direction.

Single chemoradiotherapy (CRT) was performed in 27 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy (RT) was carried out in hyperfractionated mode 1+1 Gy (every 4-5 hours), 5 times a week to CFD 60 Gy with a 2-week break after CFD 30-40 Gy. Courses of polychemotherapy (PCT) were performed simultaneously with RT at each stage of treatment. Overall 5-year survival of patients in the whole by the group (T3-4N0-3) was 44.6%, for patients with T3N0--72.7%, T3N1-20--42.9%, T4N1-2--40.0% with an average life expectancy 38.1; 50.8; 39.0 and 39.8 months respectively. During a 5-year follow-up the local control of the primary tumor at T3 was equal to 61%, T4--25% with a median remission of 40.6 and 13.5 months respectively. During this period the regional control at metastases N1 was 50%, with a median remission of 32.7 months. In 4 patients of 5 with N2 and in all 3 patients with N3 during the first year after CRT continued growth or tumor recurrence was diagnosed. Thus, conservative CRT provides relatively satisfactory 5-year outcomes in patients with tumors T3N0-1.

There were analyzed results of treatment of 58 patients with laryngeal cancer T3-4N0-3M0. Chemoradiotherapy (CRT) was carried out in 27 patients, thermochemoradiotherapy (TCRT)-in 31 patients. Radiotherapy (RT) was performed in hyperfractionated mode (1 Gy + 1 Gy with an interval of 4-5 hours) 5 times a week to CTD 52-60 Gy with a 2-week break after CTD 30-40 Gy. Local hyperthermia (LHT) was carried out 2 times a week before the second fraction of RT in an amount of 3-6 sessions. The first cycle of polychemotherapy was administered at the beginning of RT and the second one-after the break. The local control under the primary tumor category T3 after CRT was equal to 58% and after TCRT--88%, at T4--72% and 25%, respectively. Late radiation damage of the larynx in the form of mucosal edema and perichondritis after CRT was in 2 patients (7%) and after TCRT--in 3 patients (10%). Thus, TCRT for locally advanced laryngeal cancer allows obtaining a higher overall survival and a local control as compared to CRT and does not lead to a significant increase of frequency of perichondritis.

Thermochemoradiation therapy was performed in 31 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy was performed in 2 stages 1+1 Gy (every 4-5 hours), 5 times a week to SOD 52-60 Gy with a 2-week break after SOD 30-32 Gy. Local hyperthermia was carried out two times a week before the second fraction in an amount of radiation therapy sessions 3-6. In the days of local hyperthermia second fraction of radiotherapy increased to 3 Gy. Courses of chemotherapy were combined with radiation therapy and local hyperthermia at the beginning of each stage of treatment. For the whole group a complete response of the primary tumor was diagnosed in 25 (80.6%) patients, partial - in 6 (19.3%). Of the 12 patients with N1-3 complete regression of metastases occurred in 5 (41.7%), partial - also in 5 (41.7%). Five-year overall survival was 88.2% T3N0, T4N1 in 3 - 62.1%. Local control of the primary tumor in these terms in the group T3 was detected in 88.2%, in the group T4 - 77.8%, regional control of metastases with N1-3 - 33.3%. Late swelling of the mucous membrane of the larynx developed in 4 (12.9%) patients, perichondritis - in 3 (9.7%). Thermochemoradiation therapy of locally advanced cancer of the larynx provides a fairly good results comparable with those of the combined treatment.

This paper analyzes the results of combined treatment with preoperative thermochemoradiotherapy in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) 32 Gy was carried out 5 times a week with splitting the daily dose of radiation on the 2 factions (interval 4 hours) on a "1 Gy + 1 Gy," in the days of the local hyperthermia (LGT)--on a "1 Gy + 3 Gy". LGT in an amount of 3-4 sessions was performed two times a week before the 2nd fraction of RT. The course of polychemotherapy was administered concurrently with RT and LGT. In 2-3 weeks after completion of the course thermochemoradiotherapy patients were operated. Organ-saving operations were performed 10 (56%) of 18 patients with primary tumors categories T3 and 2 (20%) of 10 with T4. Postoperative wounds healed by first intention in 21 (75%) patients. The cumulative 5-year overall survival in the whole group (T3-4N0-3) was 89%, for patients without regional metastases (T3-4N0)--100%. Relapse-free survival time for those patients with a primary tumor T3 equaled 94%, T4--90%. Relapse metastases occurred in 20% of patients. Thus, preoperative thermochemoradiotherapy is a highly effective method of treatment for locally advanced cancer of the larynx and does not lead to the development of severe postoperative complications.

The study deals with the results of examination and treatment of 1040 patients with cancer (T3-4N0-3M0) of larynx and laryngopharynx. Radiotherapy was given to 358 patients concurrently with systemic polychemotherapy and different means of radiomodification. The remaining patients (682) receiving the same treatment minus systemic polychemotherapy were in control. Relapse-free (72.6%) and overall survival (82.7%) in the study group was significantly higher than in controls (54.7% and 63.4%, respectively) (p < 0.001). Moreover, an organ's function was preserved in 57.1% compared with 28.5% in control (p < 0.001).

The paper is concerned with the results of therapy of 43 patients with prostatic adenoma using local electromagnetic hyperthermia (LEH) on a Yakhta-3 unit of 915 MHz. LEH can be one of the promising methods of conservative therapy of prostatic adenoma. Therapeutic efficacy grows with increasing warming and the number of LEH sessions. LEH repeated courses of not lead to side-effects and improve the patients' local status.

Local electromagnetic hyperthermia (LEH) was applied to 29 patients with nonspecific chronic prostatitis, using UHF-units Plot or Yakhta-3 (915 MHz). Heating was achieved with the help of intracavitary areals via the rectum. A therapeutic course consisted of 6-10 LEH sessions. A direct positive clinical effect was observed in all the patients after the LEH course was over. Prostatic secretion indices returned to normal in 25 patients; a moderate leucocyte count was found in 4 patients only. Exacerbation of disease was noted in 3 patients in the course of the first year after therapy. They were given a repeated LEH course, which brought about a positive effect. Potency in 14 patients (8 of 10 with decreased potency and 6 with normal potency) was increased after LEH. LEH seems to hold promise for therapy of chronic prostatitis and its consequences. This method results in no complications, therefore LEH courses can be repeated in case of exacerbation.

The paper is devoted to comparative estimation of radiation and combined therapy of laryngeal cancer patients using combined radiomodification including local hyperthermia, total hyperthermia, chemotherapy and a method of dynamic dose fractionation. Complete and significant tumor regression at a dose of 32 Gy was noted in the study group (77 patients) and in the control group (64%). Radiotherapy against a background of combined radiomodification tends to increase the 3-year survival up to 86% as compared to 66.7% in the control group.

The paper is concerned with the results of fractionated thermal-radiation action on Brown-Pearce tumor in rabbits, sarcoma-37 (C-37) and Lewis carcinoma (LLC) in outbred and hybrid F1 (C57B1/6 x CBA) mice. Rabbit tumors were subjected to hyperthermia on UHF Plot units 4 h after irradiation, and in mice with a water-bath directly before irradiation. The frequency of Brown-Pearce tumor regression was increased as a result of hyperthermia in 4 h. The comparison of the effectiveness of fractionated radiation or thermal-radiation action on murine tumors (2 of 3 fractions for 4 days) indicated different type changes of the value of the coefficient of thermal enhancement of hyperthermia. For C-37 it was decreased with an increase in the number of fractions, for LLC it was increased, probably as a result of reoxygenation and high radiosensitivity of C-37.

The paper is concerned with the consideration of technical potentialities of local UHF-hyperthermia with regard to combined radiotherapy of endometrial cancer. The authors performed comparative analysis of thermoradiotherapy of a tumor and adjacent normal tissues and of combined radiotherapy as an independent method. The results of this investigation have shown that a decrease in a single focal dose per fraction, taking into account the DMF of hyperthermia in thermoradiotherapy, the same therapeutic effect on a tumor being preserved like in radiotherapy, reduces the frequency of radiation reactions of adjacent normal organs and tissues.

Potentiation of the effect of radiation and combined treatment of laryngeal cancer by local hyperthermia was studied in 43 patients. In 51 cases of the control group (radiotherapy), conventionally-dynamic fractionation of dose was used. At 32 Gy, complete or partial regression of tumor was observed in 72.1% in the study group and 64.7% of controls. An increased frequency of radiation-induced damage of the oral mucosa was observed whereas radiation epidermitis did not occur. Three-year relapse-free survival following a course of radical thermoradiotherapy was as high as 76.5% compared to 40% in controls. Overall three-year survival (including the results of combined treatment and treatment for relapse) increased from 66.7 to 83.3%.

In experiments on mice a study was made of the influence of serotonin, glucose, 5-FU, actinomycin D, cycloheximide, metronidazole, ethanol, novocaine, and a hypoxic gaseous mixture on the severity of skin injuries in separate and combined use of gamma-beam radiation and hyperthermia. Some agents were shown to be able to modify thermo- and radiosensitivity of tissues, in some cases the directions of changes did not coincide (i.e. sensitization to one of the injuring agents and protection by the other). In most cases the modifier summary effect in thermo- and radiotherapeutic exposure of the skin did not result in additive change of heating and irradiation. It suggested that the use of radiation modifiers in thermo- and radiotherapeutic exposure required a thorough study of the effect in each specific variant of the combination of agents.

The cell killing effect of hyperthermia (43 degrees C, 15 min) on the clonogenic Lewis lung carcinoma cells forming colonies in agar cultures in diffusion chambers was studied in vitro and in vivo. Survival rate of clonogenic tumour cells was 7.5 to 10.5%, the most prominent effect being observed in vitro. The preliminary heating resulted in 2-fold reduction of these cells' sensitivity to repeated hyperthermia. The thermotolerance effect persisted for 3 days after its induction.

The authors reported the results of measurements of the blood flow in subcutaneous fat and 3 types of tumors (sarcoma 37, Lewis carcinoma, melanoma B16) by a thermoelectric method during local hyperthermia of mouse limbs. In the first minutes of exposure the blood flow rate increased reaching a plateau in 25-35 min. Changes in the blood flow grew with raising the temperature of heating, and they were more noticeable for normal tissues than for tumorous ones. The blood flow enhancement varied in different tumors: the highest in sarcoma 37, and the lowest in melanoma B16. In some tumors after prolonged heating (over 30 min.) and at high temperature (44 degrees C) a maximum increase in the blood flow was followed by its weakening.

A study was made of the effect of various agents on skin injury by hyperthermia in experiments on noninbred albino mice. The effects of heating were assessed by the frequency of skin necrosis development. The results of the study showed that irradiation of the skin (30 Gy) before heating did not influence its thermosensitivity whereas heating 45-180 days after irradiation proved more effective. Ethanol, metronidazole, thyrocalcitonin and actinomycin D decreased skin thermosensitivity, and cyclohexamide, serotonin, hyperglycemia and applying a tourniquet increased it. The DMF value for actinomycin D depended on the temperature of heating. One should distinguish between true modification of tissue thermosensitivity (determined by cellular factors) and indirect modification (associated with change in volumetric circulation rate).

The half-period of mouse skin regeneration after sublethal injuries caused by hyperthermia (44 degrees C) was 2.9 h and completed within 16-24 h. The half-period of regeneration after sublethal injuries caused by ionizing radiation was 2.1 h at a dose of 5 Gy and 4.3 at a dose of 20 Gy. The rate of mouse skin regeneration after sublethal injuries caused by exposure to ionizing radiation only and in combination with hyperthermia at similar levels of injury did not differ.

The paper is devoted to a study of the effect of hyperthermia and irradiation used alone or in combination on the frequency and intensity of metastasizing of Walker carcinoma in rats, sarcoma-37 and 2 types (LLC and LLC-1) of Lewis lung carcinoma in mice. The frequency and intensity of metastasis depend not only on tumor type but also on a transplantation site. Metastasizing of tumor cells transplanted under the leg skin, occurs after a tumor reaches the volume of 25 mm3. Local hyperthermia (40-45 degrees C) and irradiation used alone or in combination, do not change the frequency and intensity of metastasis. However if a rise of body temperature is noted in local hyperthermia, larger tumor nodes appear in the lungs without evidence of an increase in the number of metastases.

The results of the study have shown that the proposed temperature-exposure regimen (42-43 degrees C for 30 min.) 30-40 min after metronidazole administration (1 mg per 1 g of the body mass of an animal) influences the vascularization of both normal tissues of the hip and tumors though to a lesser degree. It manifests itself in a elevation of the tone resulting in hypovascularization and a decrease in the total diameter of the vessels. This reaction is more pronounced in the first hours of the first day. The vascular system of ovarian adenocarcinoma turned out to be more reactive as compared to sarcoma 45.

Proceeding from an analysis of experimental and clinical data the authors have considered some peculiarities of the radiosensitizing effect of hyperthermia on normal and tumor tissues in different temperature exposure regimens of heating and various schemes of heating combined with irradiation. Possible importance of induced thermal tolerance in the effects of thermal radiation exposure was assessed. The analysis of studied correlations has shown that maximum development of thermal tolerance of the human skin can be induced by heating up to 41-42 degrees C and temperature inducing this effect for human tumors can be lower.

The radiomodifying and damaging effects of heating within the range of 42 degrees-46 degrees C were studied for the skin of random-bred mice. The frequency of development of skin necrosis depends on the time of heating. An increase in temperature by 1 degree C causes a 2-fold decrease in the time-period required for achieving the same effect. A radiosensitizing hyperthermal effect with raising temperature or an increase in the period of heating lessens which may be accounted for by an increased contribution of its damaging effect to the summary effect of radiothermal exposure.