Assessment of tumor infltrating lymphocytes (TiLs) has been recognized as an additional tool for predicting survival in triple negative (TN) and HER2/neu positive (HER2+) subtypes of breast cancer (BC). Recently, BC, including the above-mentioned subtypes and characterized by low/undefined expression of HER2/neu, has been isolated into a separate group, designated HER2-low BC. The relationship between clinical and morphological parameters of HER2-low breast cancer and infiltration by immunocompetent cells, including tumor associated macrophages (TAM), has not been studied to date. The purpose of the study was to identify significant relationships between the level of subpopulations of immunocompetent cells (Tils + TAM) and the clinical and morphological parameters of HER2-low BC.Material and Methods. The study examined the surgical specimens of 33 patients with HER2-low BC. Visual counting of TILs and assessment (IHC) of the level of T-helpers, T-killers, M1 and M2 macrophages were carried out in intratumor sites and the invasive edge of the primary tumor.Results. The study of mastectomy specimens showed that infiltration of Tils (Me=5 [5; 10] %) was observed in all 33 patients. The level of M2 of macrophages was found to be the highest both in the invasive margin and in the intratumor sites (CD163inv: Me=20 [10; 40] %; CD163c: Me=15 [7; 30] %, respectively). In patients with high (≥20 %) levels of M2 macrophages in the invasive margin, there was also a high level of other immunocompetent cells, and perineural invasion was detected significantly more often (р=0.019).Conclusion. A high level of infiltration by M2 macrophages of the invasive margin is combined with the detection of perineural invasion in primary HER2-low breast cancer, which is one of the predictors of a high risk of progression. In combination with other clinical and morphological parameters, the level of M2 macrophages in HER2-low breast cancer may become another factor in predicting disease prognosis.

Glioblastoma is the most frequently detected primary brain tumor (pGB), the prognosis of which significantly depends on the magnitude of residual GB (rGB), for which magnetic resonance imaging (MRI) is used in the postoperative period. Purpose: To analyze the data of ASL perfusion MRI (ASL-pMRI) performed prior to adjuvant radiation therapy (aRT), 6 to 8 weeks after resection of pGB, in terms of their prognostic significance for survival in this group of patients. Material and methods: The study included 54 patients (median age ‒ 58 years; gender: 29 men, 25 women). The Karnovsky index in 81.5 % of patients was ≥80 %. To visualize and calculate the dimensions of the rGB, ASL-pMRI was used according to the type of pseudo-continuous three-dimensional marking of arterial spins. The focus/foci of hyperperfusion (CBFmean > 64 ml/100g/min) in the area of the wall of the postoperative cyst were considered as rGB. Results: Survival in the total group of 54 patients with pGB was 18 months (95 % CI:14.23) . The use of ASL-pMRI made it possible to visualize rGB in 37 (68.5 %) patients. The probability of visualization of rGB was significantly higher (p=0.02) in the case of temporal localization of the tumor. Age (HR:1.04; 95 % CI: 1.01‒1.07; p=0.007), the maximum diameter of the rGB (HR:1.04; 95 % CI: (1.01‒1.07); p=0.03) and localization of pGB in the temporal lobe (HR:2.00; 95 % CI: 1.05‒3.80; p=0.034) had a significant negative impact on survival. The use of the multifactorial Cox model showed that only the age ≥60 years (HR:2.78; 95 % CI:1.26‒6.15; p=0.012) and the maximum diameter of rGB ≥25 mm (HR:3.35; 95 % CI:1.36‒8.22; p=0.008) retained their significant negative impact on the survival of patients with pGB. Conclusions: the use of ASL – pMRI 6 to 8 weeks after resection of pGB indicates that the results obtained can become an effective tool for predicting survival in this group of patients.

Despite the improvement of treatment methods, survival of patients with glioblastoma is still low. Glioblastoma is the most common brain tumor.OBJECTIVE:To study carbohydrate metabolism in patients with glioblastoma during adjuvant external beam radiation therapy and its impact on survival.MATERIAL AND METHODS:The study included 66 patients with glioblastoma (Karnofsky score ≥80%) who underwent hypofractionated adjuvant external beam radiation therapy (single focal dose 2.5-3Gr). Patients received dexamethasone 4-8 mg daily throughout the entire course of irradiation.RESULTS:High level of glycated hemoglobin (HbA1c) was observed in 33.3% of patients with glioblastoma undergoing irradiation. Cumulative survival was 17 months (95% CI 13.7-20.3). Two indicators had a significant negative impact on cumulative survival: age of patients (HR 1.04; 95% CI 1.01-1.08; p=0.02) and level of HbA1c (HR 1.94; 95% CI 1.23-3.06; p=0.005). Cumulative survival was significantly (p=0.022) higher in patients younger 53 years compared to older people (18 months and 14 months, respectively). Cumulative survival was 20 months among patients whose HbA1c did not exceed the upper reference value (<5.8%). Survival was higher (p=0.017) in these ones compared to patients with HbA1c ≥5.8% (13 months). According to multivariate Cox regression model, high HbA1c was the only significant negative predictor of cumulative survival (HR 3.35; 95% CI 1.14-9.81; p=0.027).CONCLUSION:High HbA1c is unfavorable predictor of cumulative survival in patients with glioblastoma and Karnofski score ≥80% undergoing adjuvant hypofractionated irradiation regardless their age.

Introduction. Despite the treatment methods’ improvement, the brain glioblastoma (GB) patient survival remains at the level of 12–14 months. In this regard, it is very relevant to optimize the choice of the treat-ment of recurrent GB, including using stereotactic radiosurgery (SRS). Materials and methods. Comparative analysis of the endothelial cells in the capillaries of blood vessels of the brain peritumoral zone (PZ) before (1 group – 32 capillaries) and 12 – 14 months after (2 group – 75 capillaries) adjuvant external radiation therapy (AERT) was performed using transmission electron micros-copy (TEM). Results. Apoptosis of endotheliocytes was observed in the capillaries of the brain PZ from 2 group much more often than from 1 group (60% and 12.6% of capillaries, respectively, p<0.001). Capillary death and thrombosis occurred in 4% and 1.4% of 2 group capillaries. An important finding was that only 69.3 of capillaries from 2 group revealed thickening of the basement membrane (BM), and 26.9% of them also revealed its peak deformation. Conclusion. 12–14 months after AERT, the brain PZ remains ischemic due to apoptosis of the capillary endothelium, thickening and peak deformation of the BM. The detected signs of revascularization of the brain PZ after previously performed AERT suggest that it is possible to consider SRS as a method of treat-ment for recurrent brain GB. Keywords: brain glioblastoma, peritumoral zone, endotheliocyte apoptosis, thickening of the basement membrane, stereotactic radiosurgery, glioblastoma relapse

Background: Glioblastoma (GB) is the most commonly diagnosed brain tumor. Its management involves adjuvant therapies, such as radiation. The cause of high probability of GB local relapse is its radioresistance related to hypoxia arising from abnormal blood-brain barrier permeability in GB vessels and in the peritumoral zone (PZ). Aim: To study pathophysiology of hypoxia in the residual GB based on the abnormalities of the morphological elements of the capillary walls building up the blood-brain barrier in GB and PZ capillaries. Materials and methods: Samples for morphological evaluation were taken during surgery for GB in 5 patients. The samples were prepared for transmission electron microscopy according to the standard technique with fixation in 2% glutaraldehyde in phosphate buffer, post-fixation with osmium tetroxide, embedding in the epon-araldite mixture, and contrast staining of ultrathin sections with uranylacetate and lead citrate. Abnormalities of the capillary cells (mitochondrial vacuolization and vacuolization of endoplasmic reticulum in endothelial cells, pericytes and astrocytes), as well as of the acellular element of the capillary wall, i.e. basement membrane, were assessed in two groups of capillaries – those of GB (n = 38) and those of PZ (n = 32). Results: Abnormalities characteristic for apoptosis and oncosis were found in the cells of the GB and PZ capillaries of the blood-brain barrier, such as endothelial cells and pericytes. However, in the GB capillaries these abnormalities were signifcantly more frequent (р < 0.001). Only half (52.6%) of the GB capillaries had an edematous pericapillary astrocyte layer. In all other capillaries, astrocyte sprouts either were visualized as separate morphological elements (13.2%) or were not visualized at all (34.2%). All PZ capillaries had the astrocyte layer, being edematous in 68.8% of the capillaries and totally edematous only in 25%. Thickened basement membrane was found in the vast majority (89.5%) of the GB capillaries and only in 25% of the PZ capillaries (р < 0.001). Conclusion: Findings of abnormal cell elements in the GB capillaries leading to peritumoral edema and consequent hypoxia are highly likely to be the cause of the remnant GB radioresistance.

The appropriate application of remote radiotherapy ensures significant increasing of survival rate of oncologic patients. The purpose of study is to determine need of the Moscow region in radiotherapy care of patients with the most frequently detected tumors on the basis of oncologic morbidity data. The calculation of minimal regional need in devices of remote radiotherapy was implemented according particular formula. In 2017, number of patients with the most frequently detected tumor localizations, requiring application of remote of radiotherapy, amounted to 4245 individuals. The minimal need in radiotherapy care for the mentioned number of patients amounted to 9.4 devices of remote radiotherapy. The optimal need of the Moscow region health care amounts to 27 devices of remote radiotherapy in case of planning of this type of medical care to all regional radiotherapy institutions in need and with consideration for indices of oncologic morbidity. The resume of carried out study testify that in radiotherapy institutions of the Moscow region health care exists an additional need in supply of such devices. The optimal perspectives of development of the radiotherapy service are outlined.

Background: Glioblastoma (GB) is the most commonly diagnosed brain tumor. Its management involves adjuvant therapies, such as radiation. The cause of high probability of GB local relapse is its radioresistance related to hypoxia arising from abnormal blood-brain barrier permeability in GB vessels and in the peritumoral zone (PZ).Aim: To study pathophysiology of hypoxia in the residual GB based on the abnormalities of the morphological elements of the capillary walls building up the blood-brain barrier in GB and PZ capillaries.Materials and methods: Samples for morphological evaluation were taken during surgery for GB in 5 patients. The samples were prepared for transmission electron microscopy according to the standard technique with fixation in 2% glutaraldehyde in phosphate buffer, post-fixation with osmium tetroxide, embedding in the epon-araldite mixture, and contrast staining of ultrathin sections with uranylacetate and lead citrate. Abnormalities of the capillary cells (mitochondrial vacuolization and vacuolization of endoplasmic reticulum in endothelial cells, pericytes and astrocytes), as well as of the acellular element of the capillary wall, i.e. basement membrane, were assessed in two groups of capillaries – those of GB (n = 38) and those of PZ (n = 32).Results: Abnormalities characteristic for apoptosis and oncosis were found in the cells of the GB and PZ capillaries of the blood-brain barrier, such as endothelial cells and pericytes. However, in the GB capillaries these abnormalities were signifcantly more frequent (р < 0.001). Only half (52.6%) of the GB capillaries had an edematous pericapillary astrocyte layer. In all other capillaries, astrocyte sprouts either were visualized as separate morphological elements (13.2%) or were not visualized at all (34.2%). All PZ capillaries had the astrocyte layer, being edematous in 68.8% of the capillaries and totally edematous only in 25%. Thickened basement membrane was found in the vast majority (89.5%) of the GB capillaries and only in 25% of the PZ capillaries (р < 0.001).Conclusion: Findings of abnormal cell elements in the GB capillaries leading to peritumoral edema and consequent hypoxia are highly likely to be the cause of the remnant GB radioresistance.

Background: Prostate cancer (PC) is one of the most commonly diagnosed tumors in the male population that makes relevant to study current trends of its incidence and related mortality.Aim: To identify current trends in РС incidence and mortality in the Moscow Region.Materials and methods: To analyze the PC incidence and mortality in the Moscow Region from 2011 to 2016, we used data extracted from the annual report forms of the federal statistic surveillance of the public healthcare and from the Moscow Regional Cancer Registry that contains regional information on newly diagnosed cancers.Results: From 2011 to 2015, the number of PC cases in men living in the Moscow Region has increased by 38%, with an average annual growth of the incidence by 8.8%. In 2016, there was a 8.7% decline in the new PC cases (in total, 1765), compared to that in 2015. From 2011 to 2015, the incidence of PC has increased from 42.5 to 57.8 per 100,000, primarily due to its change in men above their 50 years of age. In 2016, the PC incidence went down to 52.2 per 100,000. The peak PC incidence in all years of the study was in the age group of 70 to 79 years. In 2016, there was a non-significant decrease in PC-related mortality to 16.6 per 100,000.Conclusion: The results obtained can be used to optimize medical care for PC patients in the Moscow Region.

Background: Cancer of the parotid salivary gland (PSG) accounts for more than a half of all cases of salivary gland malignancies. Its treatment strategy remains a matter of debate. Aim : To identify factors significantly associated with the 3-year survival of patients with PSG cancer after combination treatment. Materials and methods : Thirty nine patients with morphologically confirmed PSG cancer (T1-4N0) were recruited into the study. Surgery (partial or total parotidectomy without the cervical lymphatic node dissection) was performed in 32 patients. The most frequent diagnosis (n = 10; 25.6% of all cases) was adenocarcinoma. Radiation to PSG and the regional lymphatic nodes was used in 15 patients as neoadjuvant and in 24 as adjuvant regimen. Three-year survival rates were analyzed in 36 patients by the Kaplan-Meier method, with consideration of their sex, age and the sequence of surgical and radiation treatment. Results : The 3-year survival after combination treatment of PSG cancer patients was 82.7%. Women, patients above 60 years of age and those who received adjuvant radiation therapy demonstrated a trend towards better 3-year survival, although it was non-significant (p > 0.05). Conclusion : Combination strategy remains an effective approach to PSG cancer irrespective of age and sex of patients. The use of radiation therapy as a single modality is possible only in exceptional cases.

Background: Cancer of the parotid salivary gland (PSG) accounts for more than a half of all cases of salivary gland malignancies. Its treatment strategy remains a matter of debate.Aim: To identify factors significantly associated with the 3-year survival of patients with PSG cancer after combination treatment.Materials and methods: Thirty nine patients with morphologically confirmed PSG cancer (T1-4N0) were recruited into the study. Surgery (partial or total parotidectomy without the cervical lymphatic node dissection) was performed in 32 patients. The most frequent diagnosis (n = 10; 25.6% of all cases) was adenocarcinoma. Radiation to PSG and the regional lymphatic nodes was used in 15 patients as neoadjuvant and in 24 as adjuvant regimen. Three-year survival rates were analyzed in 36 patients by the Kaplan-Meier method, with consideration of their sex, age and the sequence of surgical and radiation treatment.Results: The 3-year survival after combination treatment of PSG cancer patients was 82.7%. Women, patients above 60 years of age and those who received adjuvant radiation therapy demonstrated a trend towards better 3-year survival, although it was non-significant (p > 0.05).Conclusion: Combination strategy remains an effective approach to PSG cancer irrespective of age and sex of patients. The use of radiation therapy as a single modality is possible only in exceptional cases.

A high blood D-dimer level is often diagnosed in patients with malignant brain glioma (MBG), with 24% of these patients being detected with deep vein thrombosis of the leg and/or pulmonary embolism (PE). The cause of an elevated blood D-dimer level in most other cases remains unclear. The purpose of this study is to identify the features associated with an increased blood D-dimer level in patients after MBG resection, which may be used to improve the efficacy of adjuvant radiation therapy (ART).RESULTS:The study included 50 patients. Three to four weeks after resection of malignant brain glioma (MBG), the blood D-dimer level was determined in patients immediately before the onset of ART. An increase in the blood D-dimer level more than by 0.25 μg/mL was detected in 78% of patients. More often, a high D-dimer level was detected in patients aged 60 years or more. In the same age group, an increase in the D-dimer level was significantly larger (p<0.05) than in younger patients (1.2 and 0.6 μg/mL, respectively). The degree of brain tumor malignancy did not affect the rate and value of an increase in the blood D-dimer level.CONCLUSION:Our findings indicate that an increased blood D-dimer level in patients without symptoms of venous thrombosis after craniotomy for MBG is more pronounced in patients aged 60 years and over. The degree of glioma malignancy has no significant effect on this indicator.

Pulmonary embolism in breast cancer is one of the causes of major deterioration of health status of the patients. Pulmonary artery occlusion is most often a consequence of venous thromboembolism; this condition is referred to as "pulmonary thromboembolism". Significantly less common cause of occlusion of the pulmonary artery branches can be embolism by a cluster of tumor cells, accompanied by development of pulmonary tumor thrombotic microangiopathy. This paper reviews data on the etiology and pathogenesis of pulmonary embolism in breast cancer, and approaches to its prevention and treatment.

The risk of pulmonary embolism (PE) in cancer patients is 4–7-fold, compared to other patient categories. PE is the second most frequent cause of death in the first year after cancer diagnosis. PE is diagnosed in 7.5% of patients with malignant brain tumors, in 1 to 25% of those with gastrointestinal tumors, in 4.5 to 17.5% of those with breast cancer and in 4 to 10% of lung cancer patients. The risk of PE is higher with surgical interventions and chemotherapy, as well as in metastatic tumors. In 13% of cases, PE may be the first symptom of cancer manifestation. For prevention and treatment of PE low molecular weight heparin (LMWH) and warfarin are used. The risk of recurrent PE is 2-fold lower with LMWH. The frequency of bleeding with LMWH and warfarin treatment is from 14 to 19%. Placement of a cava filter is indicated only if anticoagulation is inefficient. New oral anticoagulants, which act as selective thrombin or Factor Xa inhibitors, are not used in cancer patients. Thus, diagnostics and treatment of PE is a very urgent problem in oncology that requires new approaches to be looked for.

Pulmonary embolism in breast cancer is one of the causes of major deterioration of health status of the patients. Pulmonary artery occlusion is most often a  consequence of venous thromboembolism; this condition is referred to as "pulmonary thromboembolism". Significantly less common cause of occlusion of the pulmonary artery branches can be embolism by a  cluster of tumor cells, accompanied by development of pulmonary tumor thrombotic microangiopathy. This paper reviews data on the etiology and pathogenesis of pulmonary embolism in breast cancer, and approaches to its prevention and treatment.

Background: The incidence of colorectal cancer ranks the third among all cancer incidence rates. Rectal neoplasms are frequently considered as a separate nosological entity. The incidence of rectal cancer (RC) can be influenced by patient age, gender, lifestyle, diet, genetic factors, as well as by the organization and quality of preventive activities in medical institutions focused on the early cancer diagnosis. Aim: To study changes in RC incidence among residents of the Moscow Region from 2010 to 2014. Materials and methods: The incidence rate of RC was estimated based on the state statistical report data on newly diagnosed cancers in the population of the Moscow Region in 2010–2014. The intensive incidence rates were calculated per 100,000 of respective population in six age and gender groups. Results: From 2010 to 2014, 6079 new RC cases were identified in the Moscow Region, among them 47% men and 53% women. More than half of all RC cases were in the age group of 60 to 79 years old (61.7% of men and 59.2% of women). During the 5-year period, the incidence rate of RC decreased from 18.3 to 17 per 100,000 of the male population and increased from 15.7 to 17.5 per 100,000 among the female population. There was a clear correlation between the RC incidence and the patient age. The peak incidence in men and women was seen in the age group of 70 to 79 years. From the age group of 50 to 59 years and on, the incidence of RC in men was higher than that in women. Conclusion: The results of this study can be used to optimize activities in the public healthcare system aimed at reduction of morbidity and mortality related to RC. Among the priority actions should be allocated to the development and implementation of primary prevention measures, in particular, undergo screening tests (fecal occult blood test or colonoscopy) in age groups at high risk.

Rationale: Analysis of the cancer incidence and mortality in the population is of major importance for planning of measures aimed at improvement of organization of medical care to cancer patients, ensuring high quality and availability of this type of medical care.Aim: To evaluate cancer-related incidence and mortality rates and structure among the population of the Moscow Region depending on patient gender and tumor localization.Materials and methods: The estimation and analysis of incidence and mortality rates was performed based on the Reporting Form of the Federal Statistic Surveillance #7 “Information on disorders related to malignant tumors” in the Moscow Region in 2014. For mortality analysis, including that among pediatric patients, we used data from the State Statistics Service of the Moscow Region.Results: In 2014, there were 25 600 new cases of malignancies diagnosed in the Moscow Region, that corresponded to the incidence rate of 363.2 per 100,000 of the population. The leading types of newly diagnosed tumors in men were prostate cancer, as well as tracheal, bronchial and lung cancers (54.2 and 47.0 per 100,000 of male population, respectively). In women, the highest incidence rates were found for breast and skin cancers (86.0 and 58.9 per 100,000 of female population, respectively). According to the data from Rosstat, in 2014, the overall cancer mortality rate in the Moscow Region was 228.1 per 100,000 of the population. Among the causes of cancer mortality in men, the leading one was tracheal, bronchial and lung cancer (22.2%), followed by stomach cancer (13.3%) and prostate cancer (8.1%). In women, the leading cause of cancer mortality was breast cancer (16.6%), followed by ovarian, uterine and cervical cancers (14.1%) and stomach cancer (11.4%).Conclusion: Based on the results of medical and statistical analysis of cancer incidence and mortality rates, the main direction of improvement of medical care to cancer patients and the ways for further development of specialized medical care in the Moscow Region were chosen.