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Long term results of treatment of patients with locally advanced breast carcinoma with the use of mixed photon-neutron therapy (PNT) are presented. Among 201 patients with locally advanced breast cancer receiving radiation therapy, in 95 of them it was implemented as a combination of photon and neutron radiation therapy and in 106--in the form of mega-volt photon therapy (PT). Comparative evaluation of the long-term results of treatment proved the superiority of PNT. The immediate effect after PNT in the form of complete and partial response of tumor was registered in 87.4%, and after PT--in 49% of cases. Five-year and ten-year survival rates without signs of disease after PNT were 58.1% and 29.5%, and after PT--36.4% and 7.4% respectively. Substantial differences in toxicity of techniques were not observed.

The analysis of the effectiveness of treatment was carried out in 257 patients with squamous cell carcinoma of the mucous membranes of the oral cavity and oropharynx. Two methods of irradiation were used in combination with concurrent polychemotherapy: standard radiotherapy (2 Gy 5 times a week) and radiotherapy in non-traditional modes of fractionation with uneven breaking of the daily dose into two fractions (1 Gy + 1.5 Gy or 1 Gy + 2 Gy with 4-hour intervals) to a focal dose of 60 Gy. Chemoradiotherapy with fractionated dose was more effective than standard chemoradiotherapy in frequency of objective tumor responses and regional metastases in the absence of increasing the number of early radiation reactions and late radiation damages. External beam radiotherapy in non-traditional modes of fractionation with simultaneous polychemotherapy exposure can significantly improve the results of the overall five-year survival compared with conventional fractionation technique--60.4 +/- 4.5%, 63.3 +/- 8.2% vs 27.6 +/- 10.2%, respectively.

Predictive significance of lymphoid infiltration (LI) at the boundary of tumor and intact tissue was evaluated as well as the effect of Fas-receptor (Fas) and Fas-ligand (FasL) melanoma cell expression and lymphoid infiltrate generation, on the one hand, and end results on the other. Samples of melanoma tissues from 283 patients given combined and complex treatment were examined by a single morphologist. Immunohistochemical analysis was done on paraffin-embedded bioptates from 61 patients with marked LI or without it, to assess Fas and FasL expression. Actuarial specific 5-year survival for LI(+++) was 86.7 +/- 5.6%, LI(++)--69.1 +/- 5.8%, LI(+)--45.4 +/- 5.3% +/- and LI(-)--45.9 +/- 5.9%. Most tumors were grade III-IV: more than half of them--up to 4 mm thick. Five-year survival among patients with tumors of the former group was 78.9 +/- 8.4%, 73.3 +/- 6.19%, 46.4 +/- 6.3% and 55.9 +/- 7.7%, respectively, while the latter group--90.4 +/- 5.3%, 70.9 +/- 7.1%, 65.0 +/- 6.9% and 69.7 +/- 8.0%, respectively. All samples from primary skin melanoma expressed Fas and FasL in 60.7%. No significant effect of FasL expression by tumor cells on LI generation and 5-year survival was observed.

The efficacy of adjuvant chemotherapy as a component of complex treatment for skin melanoma and that of combined treatment alone was compared. 502 patients were given combined treatment including intensive preoperative irradiation of primary foci (STD-19Gy, TTD-50 Gy, 5 days), their extended excision with or without lymphadenectomy and postoperative irradiation of regional lymph nodes. Combined treatment was administered to 124 patients; additional adjuvant chemotherapy--5-fluorouracil, methotrexate, vincristine and cyclophosphamide (4 components)--200; neo- and adjuvant chemotherapy with cisplatin and doxorubicin (2 components)--106; cisplatin, doxorubicin and dacarbazine (3 components)--29. Forty-three patients receiving individualized chemotherapy were not included in the study. None of the 502 patients showed local recurrence. Five-year actuarial survival in combined treatment group was 69.2 +/- 4.4% (M +/- m), 4-component therapy--58.2 +/- 3.6%, 2 components--68.7 +/- 4.9% and 3 components--80.0 +/- 8.3% (p0.2); 5-year recurrence-free survival- 68.1 +/- 4.4%, 57.5 +/- 3.6%; 63.1 +/- 5.0% and 60.9 +/- 10.0% respectively. No significant differences were found as far as a correlation was concerned between actuarial survival and recurrence-free one, on the one hand, and tumor stage, depth and extent of invasion, on the other. Hence, no beneficial effect of said adjuvant chemotherapeutic measures on combined treatment for locally-advanced skin melanoma was found.

Overall 194 patients with signet ring cell carcinoma of stomach were treated, 124 (64%) of them underwent combined treatment (preoperative radiotherapy with subsequent operation), 70 (36%) - only surgical treatment. There were no differences in survival rate between two groups at early (pT1) cancer. The combined method has advantages over isolated surgical at T2 tumors (both with and without regional lymphatic metastases) and at T3 tumors without regional lymphatic metastases (p=0.03). At T3N1-2 tumors with regional lymphatic metastases and T4 tumor neither combined no surgical method demonstrated positive results of treatment. Generally combined treatment with preoperative radiotherapy has statistically significant advantage (p=0.007) over surgical treatment at the patient with signet ring cell carcinoma of stomach.

An evaluation of the end results of combined treatment for osteogenic sarcoma by standard chemoradiotherapy (n = 66) and novel thermochemical therapy (n = 108) using local ultrasound hyperthermia (total number--174) demonstrated their dependence on the temperature range in target tumor tissues. Use of subhypertemperatures of 39--41-45 deg.C (TTD--36 Gy) did not improve the results of treatment. However, 41-45 deg.C (TTD--36 Gy) was followed by a significant increase in 3- and 5-year survival and improved quality of life in cured patients as compared with those receiving standard radiotherapy (TTD--60-110 Gy). Hyperthermic therapeutic effect in osteogenic sarcoma depends on certain conditions. Effective temperatures can generally be reached in patients with relatively large-size tumors and rather thin coats of subcutaneous fat.

The end-results of combined and surgical treatment of gastric cancer are compared. Survival rates were sufficiently high in both procedures in cases without extension through the serosa (T1-2) or regional metastases with adenocarcinoma cells were well differentiated (NO). However, combined treatment proved more effective in cases of the opposite situations (p=0.04-0.0001). Considering the possibility of inadequate staging, the following indications for preoperative radiotherapy are suggested: low cell differentiation, signet-cell or undifferentiated gastric tumor of 3-10 cm in diameter. In other words, early cancer of the stomach and total involvement must be excluded.

The 30-year experience with combined and surgical treatment of gastric cancer gained at the Center is discussed. The results of surgery were improved due to use of intensive preoperative radiotherapy, metronidazole and dynamic fractionated treatment. There was no correlation between intensive preoperative radiotherapy and postoperative complication incidence or lethality, irrespective of extent of surgery or lymph node dissection. Moreover, radiotherapy was followed by a considerable decrease in postoperative incidence of pancreatitis due to inhibition of secretory function by the pancreas. Use of modern technology of radiotherapy planning and implementing left virtually no serious damage. Considering the recent changes introduced to standards for surgical treatment of gastric cancer, our findings point to a safe combination of preoperative radiotherapy with extended surgical and combined treatment.

Data on 373 patients treated for cutaneous melanoma were evaluated to test a hypothesis whether there is a correlation between mechanism of protection from ultraviolet radiation and gender. Cutaneous melanoma of the extremities was identified in 63.2% of females and 26.6% of males (p0.001) versus 26.1% and 54.0%, respectively, with tumors of the trunk (p0.001). Five-year survival in women was 80.8% versus 76.9% in men in the first group (p0.2) and 59.5% and 50.0% , respectively, in the second one (p0.2). Hence, the correlation was concerned with tumor site rather than gender.

The results are evaluated of the combined treatment of 154 patients with relapsed refractory Hodgkin's disease, which was conducted using standard dosage of conventional chemotherapy. Out of those, 117 with residual lesions were randomized to receive either focal radiotherapy (20-24 Gy) in accelerated hyperfractionation (1.3-1.5 Gy, twice a day, at 5-hr interval) or 38-40 Gy in standard fractionation. Local control persisted in 85-97% of irradiated sites (median follow-up of 24 months), irrespective of irradiation technique. TTD being lowered down to 20-24 Gy due to use of accelerated hyperfractionation, the frequency of late-onset radiation injuries of paramediastinal lung tissue was lower than in standard treatment, with a subsequently lower fraction of patients with stage II fibrosis.

The paper discusses the end results of combined treatment of stomach cancer (radical surgery plus pre- and intraoperative radiotherapy). A randomized evaluation showed that it might be used for loco-regional monitoring. Five-year rates and median of survival rose significantly, as compared with surgery alone, in tumor extension through the stomach wall (T3-4), metastatic dissemination to lymph nodes (N1-2), combinations of such pathologies as well as in cases of low-differentiated, undifferentiated and signet- cell cancer.

Data on the 3-year end results of radiotherapy of inoperable localized nonsmall-cell lung cancer (286) and 5-year (98)--for chemoradiotherapy are compared. Three-year survival after hyperfractionated radiotherapy was 23.7% as compared with 11.3% when standard procedures were used. Five-year survival after hyperfractionated radiotherapy using dose escalation, induction consolidation chemotherapy with iphosphamide, etoposide, cisplatin or carboplatin rose from 3.8 to 24%, while patients were discharged 2-3 weeks earlier.

The paper discusses our findings on a phase II clinical study of an original procedure for therapy of locally advanced gastric cancer including pre- and intraoperative radiotherapy (IORT) and extended lymph node dissection. Out of 24 patients, none had intraoperative complications while postoperative ones developed in 16%; lethality rate was 4%. As far as immediate results are concerned, intensive pre- and intraoperative radiotherapy proved fully compatible with any surgical procedure including extended and extended-combined ones. Survival rates (Kaplan-Meier) were: 1 yr--90 +/- 6%; 2-, 3-year--74 +/- 9%. Indications of adjuvant radiotherapy and approaches to its effective use are discussed.

The results of definitive radiation treatment (1988-2000) for 375 patients with inoperable non-small cell lung cancer were analyzed. Three regimens of fractionation were used: (1) accelerated fractionation (AF)--(133), 2.5 Gy, 3 days a week, to a total of 47.5--55 Gy; (2) accelerated hyperfractionation (AHF)--(93), 1.25 Gy, daily, to a total of 60-72.5 Gy and standard fractionation (SF)--(149), 2 Gy, daily, to a total of 58-68 Gy. The advantages of AHF were established as regards complete regression rate (54.9% vs. 18.6%--SF and 18.1%--AF; p(0.001), median survival (30.5(2.4 months vs. 18.9 (1%--SF (p = 0.004) and 20.4 (2.4--AF (p = 0.004)), and 3-year survival (36.6% vs. 16.7%--SF (p = 0.005) and 15.5%--AF (p = 0.005). 17.9%, 9.0% (p = 0.11) and 8.1% (p = 0.08) have survived, respectively. Overall survival in the AHF group was superior in stages IIB--III; in stage I, the results were identical. Immediate response to radical radiotherapy appeared the only statistically significant factor of survival (p = 0.005-0.008) in all the groups.

The results of definitive radiation treatment for 303 patients with inoperable esophageal cancer were analyzed. Four regimens of fractionation were used: (1) accelerated hyperfractionation (AHF) (70)--1.3 Gy, twice a day, 5 weeks, to a total of 57.2-70 Gy; (2) AHF (49)--1.5-d = 1.5 Gy to a total of 54-63 Gy; (3) AHF (37)--1.7-d = 1.7 Gy to a total of 56.1-57.83 Gy and (4) standard fractionation (SF) (147) to a total of 58-70 Gy. The complete regression rate in the AHF groups (1.3-1.7, 69, 61 and 73%, respectively) was significantly higher than in that of SF (38%) (p(0.01); the median survival in the AHF groups and SF--21, 22, 12.3 and 14.3 months, respectively, and the 5-year survival 14, 12, 4 and 0%, respectively; all the differences in the groups 1.3 and SF were significant. The common independent prognostic factors for all patients were age (p = 0.04), immediate effect of radiation therapy (p = 0.01) and the length of tumor (p = 0.02).

The results of clinical application of an original method of operable gastric cancer treatment including pre- and intraoperative irradiation (IORT) and radical intervention are presented. According to a randomized study, combination treatment did not involve intra- and postoperative complication rates higher than those of surgery alone. Moreover, a significant decrease in postoperative pancreatitis was registered. IORT is a highly effective method of adjuvant treatment of operable gastric cancer. Due to its application in conjunction with preoperative irradiation and radical surgery, the end results of locally-advanced gastric cancer improved.

Theoretical, experimental and clinical rationale is discussed for selection of targets and main parameters of intraoperative radiotherapy for gastric cancer. Topometric and dosage research has been carried out. Original technological equipment has been developed for safe treatment using the domestic accelerator Mikrotron-M. Procedures for continuous relay pre- and intraoperative radiotherapy of gastric tumors in conjunction with radical surgery have been devised and adapted to operation of a specialized clinical facility.

An analysis of the data on the treatment of 91 cases of advanced cancer of the larynx showed that local UHF-hyperthermotherapy is more efficient than the SHF one as a component of radiotherapy. Use of the latter procedure was followed by a higher rate of late-onset radiation injuries. Moreover, combined application of hyper-fractionated irradiation and UHF-hyperthermotherapy involved practically no grave complications while 5-year survival increased.

More than 250 patients, mainly with locally advanced tumors of the head, neck and breast were treated with a I MeV beam of fast neutrons emitted from a BR-10 reactor. The fast neutron contribution to the total dose of the radical component of complex gamma-neutron therapy was 20-40%. Said modality was shown to improve the results of treatment for laryngeal and breast tumors. The 5-year actuarial survival following complex gamma-neutron therapy for laryngeal cancer was 89.25, while in controls--65.2% (p0.005). The 5-year actuarial overall survival in breast cancer patients treated with fast neutrons was 66.5%: gamma-neutron therapy alone--46.0% (p0.05).

Issues in physico-technological support of remote neutron therapy are discussed. On the basis of evaluation of the literature, conclusion is made that a number of important problems are still to be solved.

The results of multimodality treatment are analyzed in 56 patients with local breast cancer. Combined gamma-neutron therapy with the use of fast reactor neutrons enhances the efficiency of breast cancer treatment and does not increase the number of radiation reactions and complications. The three-year survival increased from 44 +/- 12 to 75 +/- 9%. The test reactors specifically adjusted may be useful for the radiation therapy of patients with various malignant neoplasms. Combined gamma-neutron therapy is more promising for this purpose than neutron therapy alone.

39 untreated patients with local cancer of the bladder without distal metastases were included in the trial to assess efficacy of combined drug plus radiation treatment, its toxicity and chances to preserve the bladder. The examination comprised tumor biopsy, ultrasonography, computed tomography, excretory urography and routine laboratory tests. The patients received one or two courses of intraarterial chemotherapy, radiation (50 Gy) and two doses of cysplatinum in a dose 70 mg/m2 before and after radiation. A complete response was achieved in 66.6%, partial in 12.8%, stabilization in 10.3% and progression in 10.3% of patients. One-year survival was reported in 89.7%, recurrence-free survival with functioning bladder being 66.7%. Side effects were mild and did not demand the treatment discontinuation.

Combined treatment of 111 patients with prostatic cancer stage IV including 3 components (hormones, drugs and radiation) proved superior by survival and tolerance over hormone therapy alone. Relevant dosages and regimens are detailed.

The purpose of the study was to evaluate the effectiveness of RF-hyperthermia and regional intraarterial hyperglycemia as adjuvant radiotherapy vs conventional radiotherapy of advanced head and neck cancers. Altogether 115 patients with advanced T3-T-4 carcinoma of the tongue, oral cavity and oropharynx underwent external radiotherapy (Co-60). An RF capacitative heating device operating at 40.68 MHz was employed twice a week, a total of 4 sessions per patient. Intratumor temperature was 41.5-43 degrees C. Hyperglycemia was performed via the branches of the carotid artery, a total of 3 sessions per patient. There were 4 groups (1-31 patients on conventional radiotherapy; 2-24 patients on thermoradiotherapy; 3-30 patients on radiotherapy plus regional hyperglycemia; 4-30 patients underwent combined radio-modification). A complete response was 29% for conventional radiotherapy, 67% for thermoradiotherapy, 60% for radiotherapy plus hyperglycemia, and 77% for combined radio-modification. A 2-year local control was found to be 13% for radiotherapy, 37% for thermoradiotherapy, 17% for radiotherapy plus hyperglycemia, and 35% for combined radio-modification. Only hyperthermia was found to improve a 2-year local control of advanced oropharyngeal cancer.

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.

A study was made of the results of therapy of 66 patients with maxillary cancer, of them 31 (a control group) received routine therapy by a method of summary focal dose (SFD) fractionation--60-70 Gy. In the study group (35 patients) treatment was started with large fractions at a dose of 5 Gy 2 times a week up to SFD of 20 Gy using metronidazole 2.5-3 h before each of the first 4 large fractions and continued using a course with SFD up to 52 Gy by common fractionation. Staged assessment of the results of radiotherapy was done when the summary dose reached 40 Gy in the control group and 32 Gy in the study group. Complete regression of a tumor or a decrease in its volume by more than 50% at these doses were noted in 13 (41.9%) patients of the control group and in 23 (65.7%) patients of the study group. After combined treatment of a slightly decreased tumor preirradiated in a summary dose of 40 Gy and 32 Gy the 3-year recurrence-free survival was noted in 72.2% (13 patients) in the control group and in 91.7% (11 patients) in the study group. The results obtained are indicative of a marked radiosensitizing effect of metronidazole in radical radiation and combined radiation therapy of maxillary cancer improving long-term results.

The effect of inhalation of gaseous hypoxic mixture GHM-10 (oxygen--10 +/- 1.0 and nitrogen--90.0 +/- 1.0%) on radiation response of normal tissues was studied in 184 breast cancer patients. The mixture was administered to 120 patients while 74 controls received a standard course of radiotherapy. Administration of the mixture improved normal tissue resistance to radiotherapy for breast cancer and was followed by lower incidence of long-term radiation injury, lower frequency and shorter duration of general vegetative reactions to radiation.

Proceeding from an analysis of the literature and their own data on radio- and thermodifying properties of hyperglycemia the authors have proposed a scheme of polyfactor therapy of malignant tumors including the following succession of exposures under clinical conditions: irradiation (the 1st fraction)--a chemotherapeutic drug--hyperglycemia--hyperthermia--irradiation (the 2nd fraction). The interval between exposures should be the least, best of all exposures should follow one another in a quick succession. Using the experimental data for determination of methods of therapy of transition and metastatic tumors of the upper respiratory tracts, satisfactory clinical results were obtained with regard to survival and the absence of local radiation reactions.

The paper is concerned with the results of gamma-beam therapy of 120 patients with inoperable lung cancer using the fractionation of a common daily dose of 2-2.2 Gy into 2 equal fractions as a variant of super-fractionated irradiation used in clinical practice. The direct and short-term therapeutic results were improved: a complete tumor regression rate determined by x-ray was 26.7%, a 2-year survival rate 19.2%. In the group of patients who were irradiated by the commonly used methods, the same values were lower. Improved tolerance of therapy with fractionation of a common daily dose was noted.

The paper is concerned with the results of radiation and combined therapy of 153 laryngeal cancer patients. Of them 103 received radiotherapy combined with metronidazole at a dose of 5-8 g/m2 2.5-3 h before an irradiation session, 50 patients were controls. Radiotherapy was given by mean fractions at a dose of 5 Gy 2 times a week with a summary focal dose of 20 Gy with subsequent irradiation at a daily dose of 2 Gy up to a summary dose of 32 Gy. The efficacy of radiotherapy was evaluated after a 2-week discontinuation. In a complete resorption or lessening of a tumor volume by more than 70% radiotherapy was continued by conventional fractionation at a daily dose of 2 Gy up to a summary focal dose of 52 Gy. In insignificant lessening of a tumor volume the patients were operated on. The use of metronidazole in a radical course of radiotherapy of laryngeal cancer patients did not improve therapeutic results, however the number of postoperative complications caused by surgical treatment for tumor recurrences increased 3 times. In combined treatment of the laryngeal cancer patients after a summary focal dose of 32 Gy and 1.5-3 years of follow-up the number of the patients increased up to 75.7% as compared to 50% in the control group. A decrease in the number of postoperative complications was noted.

A study was made of the comparative results of radiotherapy of 332 laryngeal cancer patients of whom 237 were treated by routine methods and 95 by multifractionation (double fractionation of a daily dose by 1 Gy with a 4-5 h interval). The method of dose multifractionation was mathematically substantiated. Direct efficacy of radiotherapy was assessed in the delivery of a dose of 40 Gy. A radical dose of irradiation was 66-70 Gy. At 40 Gy complete tumor resorption in the patients of the control group was noted in 33.3% of the cases, in the study group in 58.9%. The 3-year recurrence- and metastasis-free survival rate after radical radiotherapy was 47.4% in the control group and 65.3% in the study group. A decrease in the number of late postradiation edema of the laryngeal mucosa from 28.7% in the control group to 8.7% in the study group was noted.

The paper is concerned with an analysis of the results of concomitant therapy of corpus uteri cancer, Stage I-II, in 70 patients with relation to the regimen of intracavitary irradation using high energy sources on the Agat-B afterloading unit. Therapeutic efficacy, the frequency and severity of radiation complications were evaluated depending on the regimen of contact irradiation. Short-term results of concomitant radiation therapy were improved when passing over from a scheme of intracavitary irradiation of 10 Gy a week to schemes of dynamic fractionation and twofold irradiation a week at a dose of 5 Gy. The authors emphasize the inappropriateness of the use of large focal doses of 10 Gy during contact irradiation with high energy sources because in these cases exceeding tolerance of normal tissues is observed, particularly in patients of advanced age with noticeable somatic pathology.

The paper is concerned with the results of clinical examination of 44 patients with prostatic cancer and their distribution according to disease stages. The authors provide morphological evaluation of the data (cytological and histological confirmation of the diagnosis). In the data analysed most of the patients had T3 and T4-34 (77.3%), i. e. patients with poorly differentiated tumor forms. All the patients were given a radical course of gamma-beam therapy of the prostate, 19 of them took estrogens prior to irradiation. Moving gamma-beam therapy of prostatic cancer is well tolerated by patients. It can be used in any stage of disease and in the progression of disease as well. Radiation reactions in the form of epitheliitis of various degree in the inguinal region were noted in 15% of the cases at a dosage of 32-44 Gy. Short-term results of the treatment were good: subjective signs of improvement were observed in 99.7% of the patients, objective signs of a positive therapeutic effect in 21 (48.1%). The 3-year survival rates were 44.3% for patients after a radical course of radiotherapy and 32.6% in radiotherapy for patients with tumor progression.

A model of a system of dosimetric design of radiotherapy on the basis of SM-4 and ES-1033 computers has been developed and is being tested. Radiotherapy for over 600 patients with tumors of different sites was designed within 1 year. The simplicity of the system allowed a radiologist to take an active part in the choice of a favourable radiotherapy design. Four variants of dose distributions on an average were computed for each patient. A study of the time characteristics of the system has shown that the time of input of the data on a patient and beam parameters does not practically depend on the computer speed and lasts for an average of 15 min. Dose field computation and optimization of inputs vary from 0.4 to 6 min. depending on a volume of computation and computer type. A one-task computer system with one working place and memory is able to meet the requirements in dosimetric design for 2-3 radiotherapeutic units. More units will require multitask and all-purpose computers with 2 and more working places. Minimum standards of computer memory and speed are the same as in the first case.