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Design of non-transferred DC electric arc plasma torches (EAPTs) operated with plasma gases containing alkane hydrocarbons, as a promising type of heaters for a number of technologies (thermal spraying, surface hardening, testing of thermal protection systems, etc.), requires taking into account the evaporation rate of surface cathode material (as one of the channels of its ablative degradation). For this procedure, as the first stage, thermodynamic methods can be used to simulate the composition and properties of reactive C–H–O–N–Ar–Me-systems with variable set of such input parameters as the ratio of components of plasma-forming mixture, its pressure and temperature. We theoretically estimated the evaporative degradation of the material for three variants of EAPT cathode with alkane-containing plasmas (“hot” thermochemical zirconium and thermionic tungsten, and “cold” copper) in equilibrium and quasi-equilibrium modes of “plasma gas + surface cathode material”-mixture, with use of generalized thermodynamic properties of the materials. The calculation for conditions with pressure, which is characteristic for EAPT discharge chamber, showed that when varying the initial composition of the plasma-forming mixture (from oxidizers (air or combustion products of alkanes) to reducing gases based on the products of combined partial oxidation and pyrolysis of alkanes), the effect of a difference in the cathode evaporation rate EAI was observed in systems based on (air + alkane)-mixtures near the melting point of surface cathode substances, in a comparison with the case of EAPTs with more conventional gases (commercial N2, air) and, importantly, for two variants of the analyzed cathodes (with the exception of copper). In addition, the electrode erosion value was compared for simulated zirconium cathode (in terms of erosion evaporative component) when operating on the combustion products of alkanes from “air + CH4”-mixture, and for some known EAPTs with similar cathodes in other gases. Using the case of earlier tested DC plasma torch with rod Zr-cathode (with microheterogeneous surface) as an example, it was found that our calculation indicates non-monotonic dynamics of EAI value and fractions of Zr-containing vapors as a result of the change of the fuel-air equivalence ratio f of initial reactive mixture. This effect is inconsistent with measured cathode composition, which shows a probability of nonequilibrium character of thermal and diffusion processes in near-electrode plasma and surface layer (~1 mm) of the electrode, at least in the modes with arc current in the torch near 300 A. Besides this, it should be noted that obtained modeling data on the behavior of zirconium compounds (ZrO2, ZrC) in C–H–O–N–Ar–Zr-system can be used not only for improvement of the torch cathodes, but also for design of new Zr-containing thermal protection systems to predict preliminary their ablation rate in a flow of products of combustion (including incomplete one) of engine-, rocket- and other fuels. Similarly, the results on the copper compounds behavior near the metal evaporation temperature can be useful for optimizing the process of plasma spraying of copper alloy coatings.

Over the past few years, a group of new processes was developed for high-temperature, including plasma electric arc spraying (at ambient pressure) and spheroidizing of some ceramic and metal powder materials with the use of gaseous hydrocarbons in the heat carriers as well as with feeding of organic additions into a high-temperature jet, in particular, polymeric ones, to control porosity of sprayed metallic functional coatings. The paper considers the possibility to modify such technological processes by introducing solid fuel additions of a polymer type into the operating fluid of an apparatus for gasthermal (plasma or other) treatment, which provides melting of metal or oxide powders. For this, with the help of thermodynamic analysis, the processes have been evaluated at temperatures (300–3000) K for the set of such reacting five component systems as C–H–O–N–Me (at ambient pressure 0.101 MPa) with five variants of Ме – aluminum, titanium, chrome, copper, nickel. This makes it possible to consider these systems as simulants for potential technologies for the treatment of oxide powders (Al2O3, TiO2, Cr2O3) as well as metallic ones (Cu, Ni and their alloys). In order to obtain high exothermic contribution to the heating of powders, the combination “air + polymeric addition (polyethylene) of LDPE grade” was chosen as mixed heat carrier (operating fluid) for the basic version of simulated process. During the analysis of equilibria for the considered multicomponent systems (17 variants), a set of following parameters has been used to characterize the energy intensity of the target powder heating process: the equivalence ratio for reacting mixture and its adiabatic temperature; the energy efficiency of material heating with and without taking into account the effect of fuel addition; specific energy consumption for the powder melting; autothermicity degree of the process during the combined heating (electrothermal heating by the arc of plasma torch and heat flux from the “air + solid fuel additions” mixture) of refractory powders. As a result of the assessment, the preferred (from thermodynamic standpoint) regimes of the considered processes have been found and the possibility to realize an energy-efficient heating of these oxide and metal materials (without oxidation of the latter to CuOx, NiO) with a reduced part of the electric channel of energy transfer, resulted from the carrying out of appreciable effect of the fuel-initiated mechanism of heating in the analyzed C–H–O–N–Mesystems, has been shown in the paper.

A physical and chemical investigation of ceramic materials based on manganites of mixed rare earth elements – La0,8-хLnхCa0,2Mn0,94Cr0,04Ni0,02O3 – for electrochemical and catalytic applications has been carried out, and they were obtained from nitrate feedstock based on industrial-type polylanthanide concentrate, which corresponds to typical bastnaesite ore on the ratio of rare-earth elements in it. For polycrystalline samples of the obtained materials, the formation of single-phase structure or more often two-phase one has been identified after sintering in air at 1500 K, i. e., a the mixture of cubic perovskite phase based on low-cerium or A-site deficient manganite and a fluorite phase based on CeO2 with dioxide content of 54–98 %. A phase formation mechanism has been proposed, which is possible during the transition to compositions with rising cerium content at a constant sintering temperature of manganite materials. The effect of the chemical composition and structure of the materials on their conductivity and density, reached by the sintering, has been established in the paper. Investigation of electrical conductivity has shown that in the manganites the semi-conductive behavior/ charge transfer mechanism (p-type) is realized at the temperature range of (300–1270) K. The maximum conductivity within the range of (290–1270) K is achieved in this low-cerium bastnaesite-type system for a two-phase material with the composition La0,8-хLnхCa0,2Mn0,94Cr0,04Ni0,02O3 at x= 0.6 and is 39 S/cm at a density level of 50 % of the theoretical one for a ceramic sample. Manganite materials with lanthanum substitution, such as investigated polylanthanide-based ones, can provide a lower cost for fabrication of electrochemical and other devices based on them, taking into account the complex prices dynamics on the markets of rare-earth raw materials during the last decade.

Lung cancer still holds the leading position in terms of morbidity and mortality, both among men and women. The five-year survival rate for lung cancer is one of the lowest among cancers and varies from 5% to 15% for different countries. The study of new directions in the treatment of this nosology is an extremely urgent problem at the present time. The most common histological variant is non-small cell lung cancer. The presence of driver mutations (EGFR, ALK, ROS1) makes it possible to use targeted therapy in these patients. However, in the absence of driver mutations, the treatment of disseminated non-small cell lung cancer is still based on chemotherapy, which has a low efficiency, making up only about 30% in the first line of treatment. A promising approach to the treatment of this group of patients is the use of immunotherapy, in particular anti-PD-1 and anti-PD-L1 checkpoint-inhibitors. In large randomized international clinical trials, pembrolizumab and atezolizumab were shown to be effective in the first line of treatment, and nivolumab in the second line of treatment. Moreover, according to meta-analyses on the effectiveness and safety of immunotherapy, PD-L1 inhibitors (atezolizumab, avelumab, and durvalumab) have a lower toxicity profile compared to PD-1 inhibitors (pembrolizumab and nivolumab). This article presents a clinical observation of effective treatment of a patient with disseminated non-squamous non-small cell lung cancer with a combination of atezolizumab with bevacizumab and chemotherapy. The partial effect of treatment achieved in this patient is maintained for 3 years without the unacceptable toxicity.

Anaplastic lymphoma kinase (ALK) translocation is a rare genetic disorder that underlies lung cancer development. As a rule, these are young people, people with no or little smoking experience in whom the diagnosis is made at a late stage of the disease, when there are distant metastases; the liver and brain are often affected.The right choice of treatment policy in patients with ALK-positive non-small cell lung cancer can significantly improve survival rates. And molecularly targeted therapy with ALK inhibitors is effective even in these cases.Crizotinib (Xalkori). is the first ALK inhibitor that has been proven its antitumor activity. However, despite the initial pronounced antitumor effect, most patients develop drug resistance after 1–2 years of administration to krizotinib. In this case, the prescription of the second-generation drugs alectinib (Alecensa) and ceritinib (Zykadia) allows half of the patients to achieve a long objective response. Nevertheless today, alectinib in first-line demonstrates the best long-term results: the median progression-free survival is more than 34 months, 4-year overall survival rate is 64.5%. The drug has been shown a high activity in patients with brain metastases. Alektinib therapy not only has an advantage in terms of survival over Crizotinib, but also has an acceptable safety profile. This opens up new perspectives in the treatment of ALK-positive patients.

The objective of the study was to assess the feasibility of using CA -62 marker of epithelial carcinomas for monitoring treatment response and detecting cancer progression or recurrence during chemotherapy.Material and Methods. A 12-month double-blind clinical trial was conducted by two independent groups: clinical oncologists and biochemists, and involved 89 patients with different cancers confirmed by histopathological findings. The other inclusion criteria were: the presence of at least one measurable lesion according to the RECIST criteria, ECOG performance status 0-2 and satisfactory laboratory parameters. The expression of CA -62 cancer marker was measured by immunochemiluminescent assay used for the detection of epithelial carcinomas.Results. The elevated level of CA -62 marker was observed in 76 patients before starting the treatment. After completion chemotherapy, the level of this marker decreased to the normal reference ranges (

The treatment efficacy and toxicity profile was evaluated in 33 patients with highly differentiated neuroendocrine tumors NEO (G1, G2), who received sunitinib therapy in various dose regimens. Stable disease was achieved in 24 patients (72.7%), partial effect in 1 patient (3%). The efficacy of treatment did not depend on the used dose regimen. The toxicity profile was consistent with international study data.

Gastric cancer (GC) is one of the most common types of malignant tumour worldwide and is ranked fifth in the cancer incidence pattern and third in the cancer mortality pattern. In the Russian Federation, 39.9% of patients are diagnosed with stage IV gastric cancer, 46.6% of patients die within the first year after diagnosis. The combinations of trastuzumab with platinum derivatives and fluoropyrimidines (trastuzumab + doublet) are regarded as the standard therapy against HER2 positive disseminated gastric cancer. We studied the efficacy and toxicity of the combination of trastuzumab with three-component (triple) chemotherapy regimens (docetaxel or irinotecan + platinum derivatives and fluoropyrimidines). In combination of trastuzumab with triplet chemotherapy, an objective response was achieved in 76.7% of cases, with doublet chemotherapy it was achieved in 60% (p = 0.228), of which complete tumour regression was observed in 10%, control of the disease was reported in 96.7% and 95.0 % (p = 1.0) patients, respectively. The median progression-free survival in patients, who received trastuzumab in combination with triplet chemotherapy, was 9.66 months, in combination with doublet chemotherapy was 11.07 months, the difference was not statistically significant (p = 0.800; OR = 0.908; 95% CI: 0.430–1.918). Median survival of patients is not achieved. The obtained results showed that adding a third cytostatic agent to the standard duplet chemotherapy in combination with trastuzumab does not lead to improvement in the treatment outcomes of first-line therapy in patients with HER2-positive disseminated gastric cancer.

Background: Several studies show that the combination chemotherapy with ramucirumab allows to improve the treatment results of advanced gastric cancer (GC). Irinotecan with fluoropyrimidines is own of the second line chemotherapy options for these patients. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of irinotecan and fluoropyrimidines with ramucirumab in metastatic GC.Methods: Eligible patients had advanced morphologically verified GC and disease progression during or within 4 months following first-line therapy. They received FOLFIRI plus ramucirumab (8 mg/kg on day 1) or XELIRI in combination with ramucirumab (8 mg/kg on days 1 and 8). The primary end point was progression-free survival (PFS). Secondary end-points were disease control rate (DCR) and safety.Results: Between September 2015 and April 2019, 39 patients (pts) were enrolled and 38 were evaluated for efficacy and toxicity. Median number of cycles was 9 (2-20). Seven patients achieved a partial response (PR) for an overall response rate of 17.9%. A total of 29 (74.4%) patients had stable disease (SD) for a DCR of 92.3%. With a median follow up 7,5 months, median PFS was 7.58 months (95% CI 6.6-8.5) and the median OS has not yet been reached. Median duration of PR response was 8,7 months (4,11-10,94+) and median duration of SD was 4,14 months (1,84-11,99+). The main treatment-related grade 3 or 4 adverse events were neutropenia (7/38; 18.4%), anemia (1/38; 2.6%) and diarrhea (2/38; 4.3%).The most frequent adverse events of special interest (AESIs) any grade were hypertension (16/38; 42.1%), bleeding/hemorrhage (10/38; 26.3%), proteinuria (6/38; 15.7%) and venous thromboembolic events (10/38; 26,3%). Gastrointestinal perforation developed in two patients (2/38; 5.3%). No treatment-related deaths occurred.Conclusion: In our research ramucirumab with irinotecan and fluoropyrimidines demonstrate the high activity and a manageable safety profile in patients with pre-treated metastatic GC

. The photocatalytic activity of three systems, promising for chemical water purification technologies, was experimentally compared, based on a combination of titanium dioxide/(Fe(II, III)), applying to the model oxidation reaction of methylorange organic dye in an aqueous medium. Herewith the cases of photocatalytic systems were investigated, which are based on: a) titania hydrosol obtained by hydrolysis of titanium isobutylate; b) a similar hydrosol with addition of Fe(III) ions; c) suspension of ilmenite powder based on FeTiO3. As a result of the investigation, the increase of the rate of destruction of methylorange by more than two times was found in the system with the introduction of a small amount of iron ions into initial suspension of the TiO2 hydrosol (at the obtaining a medium with the Fe3+ concentration up to 3.7 × 10–5 M). In the photocatalytic system, based on the suspension of pretreated (with suphation and calcination) ilmenite powder, enough high photocatalytic activity (the degree of methylorange decomposition up to 77 %) was measured but at a higher exposure than for the case of systems based on the TiO2 hydrosol. For the photocatalytic systems of the type being investigated, a possible mechanism of increasing their oxidative activity was briefly considered, which requires an additional physico-chemical analysis.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare epithelial tumors that arise from cells with a neuroendocrine phenotype. NENs are found in the gastrointestinal tract and pancreas – 60 % of all localities. The incidence of gastric NENs is about 9 % of all neuroendocrine tumors of the gastrointestinal tract and 0.3 % of all stomach tumors. Stomach neuroendocrine tumors (NETs) are classified into three clinico-pathological types, based on etiology, pathogenesis and morphology. There are also separate neuroendocrine cancers: small- and large-cell. The prognosis and approach to treatment of various types of gastric NENs differs significantly. Modern methods of instrumental diagnostics, immunohistochemical methods of morphological research, along with light microscopy, do not always allow us to accurately assess the malignant potential of a tumor and individualize the treatment process. One of the promising directions in the study of NETs is to determine the molecular mechanism underlying their development, in particular the role of microRNAs. This direction can open a new vector of understanding the pathogenesis, determining the prognosis of the disease, as well as finding new application points for the drug treatment of NETs. MicroRNAs are a class of short non-coding RNA molecules (18–25 nucleotides). MicroRNAs can be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. A study of microRNA expression in tissues revealed tumor-specific microRNAs. In contrast to a number of other malignant tumors, microRNA expression in patients diagnosed with NENs is poorly understood. MicroRNA-222 and microRNA-202 are among the few microRNAs that have been demonstrated in the NETs of the stomach.

Background. Working out of the second line chemotherapy of advanced gastric adenocarcinoma is a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma that has progressed on or after prior fluoropyrimidineor platinum containing chemotherapy based on data of REGARD and RAINBOW trials.Materials and Methods: From June 2016 to 15Jan 201837 pts with advanced GC were treated with ramucirumabin the second line treatment as single agent (11 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Results: edian PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 4,0mons, MOS -10,6 mons. Ramucirumab had an acceptable safety profileConclusions:ur data are similar to the data of international randomized trials.

Ramucirumab is a monoclonal antibody targeting vascular endothelial growth factor receptor 2. In two randomised clinical trials Ramucirumab either alone or in combination with paclitaxel has been found to be safe and effective for patients with previously treated advanced gastric cancer. One of the serious adverse events associated with ramucirumab is bleeding.We report the case of a 56-year-old man with advanced gastric cancer located at the gastroesophageal junction with liver, pulmonary and multiple lymph node metastases, plevritis was treated with a paclitaxel plus Ramucirumab regimen. We demonstrate a case of a cardioesophageal junction bleeding due to the high efficiency of treatment. He was successfully treated with by applying only hemostatical therapy, but after stop the bleeding chemotherapy was not reintroduced. The partial response was maintained for approximately 10 months. The patient died on 28 November 2017.Chemotherapy with best supportive care for metastatic gastric cancer shown the improvement the performance status, help keep the cancer under control and help relieve symptoms during the time.

Advanced well differentiated neuroendocrine tumors (NET) have poor sensitivity to chemotherapy. Biotherapy and targeted therapy are the main treatment options for these patients. Approaches to the 2nd and subsequent lines of treatment have not been developed to date. VEGFR blocker bevacizumab is actively studied in well differentiated NET. For well differentiated NET, it has been shown that an increase in VEGF expression is associated with metastasis and decrease in progression-free survival.

Angiogenesis has become an important target in the treatment of solid tumors and anti-angiogenic agents are a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC) that has progressed on or after prior fluoropyrimidine – or platinumcontaining chemotherapy based on data of REGARD and RAINBOW trials.We evaluated the progression free (PFS), overall survival (OS) and safety of ramucirumab in patients (pts) with advanced GC in routine clinical practice From June 2016 to 20 Sep 2017 40 pts with advanced GC were treated with ramucirumab in the second line treatment as single agent (8 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Median PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 5,02 mons, MOS was not reached. Ramucirumab had an acceptable safety profile Our data are similar to the data of REGARD and RAINBOW trials.

Parathyroid carcinoma (PC) is a rare neoplasm with a prevalence of only 0.005 % of all malignancies, and less than 1 % among patients with primary hyperparathyroidism. The diagnosis can be challenging due to the rarity of the disease, similarity of clinical features to parathyroid adenoma, and lack of reliable morphological signs of the tumor. For metastatic cancer of the parathyroid gland does not exist standard drug therapy due to the rare occurrence of this disease. Chemotherapy and radiotherapy failed to show any significant effect on the course of the disease. We report the case of a 27-year old woman with PC previously misdiagnosed as benign thyroid nodule and multiple lung metastases. After the immunohistochemical study and confirm of diagnosis PC the patient was treatment with multikinase inhibitor sorafenib successfully.

The effectiveness of traditional chemotherapy (with temozolomide, fotemustine, lomustine) alone or in combination with whole brain radiotherapy in melanoma patients with cerebral metastases does not exceed 7–10 % with no significant impact on survival, which is around 2–4 months. Targeted therapy helped to improve survival of patients with disseminated melanoma and BRAF V600 mutations. The use of targeted drugs in patients with brain metastases allows to control the tumor process and to succeed in treatment of cerebral metastases. According to currently available research data and our own results, the effectiveness of targeted therapy with vemurafenib in melanoma patients positive for BRAF V600 mutations with brain metastases reaches 18.0–44.5 % with median survival of 5.3–8.0 months. Evidences suggest that the use of vemurafenib in melanoma patients with brain metastases ensure effective disease control in most of the cases and has a significant advantage comparing to conventional chemotherapy and whole brain radiotherapy. According to the results of these studies vemurafenib can be recommended as a 1st line targeted drug for treatment of melanoma patients with BRAF V600 mutations and brain metastases. Despite the existence of blood-brain barrier and efflux systems, new targeted drugs showed promising results in treatment of brain metastases. Over the last few years we have enhanced our understanding of brain metastasis mechanisms, principles of blood-brain barrier functioning, and ways of cancer drugs penetration into the central nervous system. Targeted therapy is constantly developing and will play an increasing role in treatment of melanoma cerebral metastases in the future with finding of new targets.

Objectives: to assess the feasibility of a combination of the intensity-modulated radiation therapy (IMRT) with a triplet chemotherapy with paclitaxel, capecitabine, and mitomycin C in the treatment of patients with anal cancer, and to evaluate the toxicity of the proposed treatment regimen.Materials and methods. All patients included in the study had stage I–IIIB anal cancer. All patients underwent IMRT radiotherapy 52–58 Gy (the dosage is calculated according T symbol) by 1.8 to 2.2 Gy fractions daily. The proposed chemotherapy scheme includes mitomycin C 10 mg/m2 on day 1, paclitaxel 45 mg/m2 on days 3, 10, 17, 24, 31, capecitabine 625 mg/m2 during radiotherapy. A complete response to treatment after 26 weeks, and the compliance to the study protocol were the primary end points of the study.Results. The study included 38 patients. Among patients stage I anal cancer occurred in 1 (2.6 %) case, II – in 5 (13.2 %), IIIA – 15 (39.5 %) and IIIB – in 17 (44.7 %). A significant deviation from the protocol reported in 6 (15.8 %) patients, in 11 (28.9 %) patients a slight alteration from the treatment was documented, and 21 (55.3 %) patients completed the treatment of chemoradiotherapy with full compliance to the study protocol. The high profile of toxicity (grade III–IV) was recorded in 23 (60.5 %) patients. An incomplete clinical response at 26 weeks after treatment was reported in 5 (13.2 %) patients, one whom continued watchful waiting and achieved complete response at 9 months posttreatment. Median followup was 27 months. 1 patient developed a local recurrence 1 year posttreatment.Conclusions. The proposed triplet chemotherapy regimen using IMRT is feasible and has acceptable toxicity. For further assess the continuous research is needed.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. The prognosis of advanced gastric cancer remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. Many targeted-therapies failed to show a significant survival benefit in GC, only 2 of them are approved FDA: trastuzumab in the 1-st line treatment of HER2-positive gastric cancer and ramucirumab with or without paclitaxel as second line chemotherapy. The article presents the case of effective treatment of patient with Her2-negative advanced gastric cancer. A 76-year-old man had a moderately differentiated adenocarcinoma of gastric with synchronous multiple liver metastases. He received ramucirumab with paclitaxel as second -line chemotherapy. The size of the liver metastases was reduced and he maintained a partial response for one year. This clinical case report demonstrates that new option in the treatment of advanced gastric cancer can to allow our patients to live longer without losing the quality of life.

Analysis of latest trials, comparing treatment schemes including chemotherapy with anti-EGFR monoclonal antibodies or bevacizumab is presented in this article. The data in these trials is inconsistent, but detailed analysis of FIRE-3 trial allows to distinguish a wild-type RAS patient group that benefits most from chemotherapy with cetuximab or panitumumab as 1st line metastatic colorectal cancer treatment. A final analysis of this patient group in CALGB/SWOG 80 405 trial is pending. The RAS analysis is pivotal for choice of 1st line chemotherapy.

In patients with kidney cancer (KC), the rate of metastatic brain involvement is 2-11%, is steadily growing, and is one of the important reasons for treatment failures in these patients. Surgery and radiotherapy, including radiosurgery, must be considered as optimal treatments for patients with KC and brain metastases. Systemic drug therapy has recently played a more and more increasing role in the treatment of patients with a progressive brain tumor process. At the same time, there are no exact pharmacokinetic data on drugs registered for the treatment of disseminated KC in respect to their concentration in the human central nervous when they are used in therapeutic doses. On the basis of the data of the literature review and the results of the authors’ studies, it may be concluded that while none of the target agents has still shown any significant advantage over others in treating KC patients with brain metastases. All the drugs have demonstrated their ability to achieve a clinical and X-ray verified objective effect (as stabilizations in most cases) in treating brain metastases. The most data are available on the therapeutic efficacy of sunitinib and sorafenib. In case of progressive brain tumor process, drug treatment should be individually discussed in each situation in accordance with standard approaches to treating patients with disseminated KC.

Results of studies performed have shown high efficiency of drug therapy for treatment of patients with breast cancer (BC) with brain metastases. The best results regarding survival rate have been achieved for treatment of BC patients with brain metastases and HER2 hyperexpression. At present, studies are performed regarding examination of new anticancer drugs and their use in combination with radiotherapy for treatment of BC patients with brain metastases. It is necessary to perform studies of efficiency of various schemes of drug therapy depending on biological properties of the primary tumor. The issue of sequence of application of drug therapy and radiotherapy for metastatic brain lesions also remains actual.

The paper considers the experience with capecitabine in 67 patients with brain metastatic lesion from breast cancer. The immediate efficacy of capecitabine and the results of therapy with the agent were analyzed in the groups of its use alone and in combination with radiotherapy both for therapeutic purposes and as an adjuvant regimen. In the chemoradiation therapy group, the objective effects in the brain were 73 %. The median time to progression was 12.27 months. In the monochemotherapy group, the objective effects were 30 %. The median time to progression was 4 months. The results of the investigation show that capecitabine has pronounced antitumor activity and moderate toxicity. Combination treatment is the method of choice.

Retrospective analysis of 3 randomized clinical trials of WT-KRAS metastatic colorectal cancer patients (PRIME, PEAK, FIRE-3) is presented. The PRIME study demonstrated increase in median overall survival (OS) in group receiving panitumumab in addition to FOLFOX4 chemotherapy – 26.0 vs 20.2 months (р = 0.04). The РЕАК trial compared FOLFOX4 + panitumumab and FOLFOX4 + bevacizumab in the same patient group in first-line treatment, a significant increase in median PFS (13.1 vs 9.5 months, p = 0.03) and non-significant increase in median OS (41.3 vs 28.9 months, p = 0.058) was achieved. The FIRE trial demonstrated FOLFIRI + cetuximab superiority when compared to FOLFIRI + bevacizumab in median OS 33.1 vs 25.6 months (р = 0.011). All trials retrospectively analyzed additional RAS mutations, allowing to select a subgroup of patients, who benefit most from EGFR inhibition.

The review literature regarding endovascular interventions for rectal cancer treatment is presented. The results of treatment of loco-regional rectal carcinoma by with the help of endovascular selective lipiodol oil chemoembolization of the rectal arteries, and also the data concerning features of blood supply of rectum, received by selective angiography are presented. The results confirm expediency of endovascular methods in treatment of rectal cancer considering specific features of blood supply of rectum.

One of the problems facing chemists who are involved in obtaining disperse systems with micro- and nanoscale particles of the disperse phase is a size evaluation of the obtained particles. Formation of hydrated sol is one of the stages for obtaining nanopowders while using sol-gel-method. We have obtained titanium dioxide hydrosol while using titanium tetrachloride hydrolysis in the presence of organic solvent with the purpose to get titanium dioxide powder It has been necessary to evaluate size of titanium dioxide hydrosol particles because particle dimensions of disperse hydrosol phase are directly interrelated with the obtained powder dispersiveness.Size calculation of titanium dioxide hydrosol particles of disperse phase has been executed in accordance with the Rayleigh equation and it has been shown that calculation results correspond to experimental data of atomic force microscopy and X-ray crystal analysis of the powder obtained from hydrosol.In order to calculate particle size in the disperse system it is possible to use the Rayleigh equation if the particle size is not more than 1/10 of wave length of impinging light or the Heller equation for the system including particles with diameter less than wave length of the impinging light but which is more than 1/10 of its value. Titaniun dioxide hydrosol has been obtained and an index of the wave ration has been calculated in the Heller equation. The obtained value has testified about high dispersiveness of the system and possibility to use the Rayleigh equation for calculation of the particle size in the disperse phase. Calculation of disperse-phase particle size of titanium dioxide hydrosol has corresponded to experimental data of the atomic force microscopy and X-ray crystal analysis for the powder obtained from the system.

The BCIRG 001 study has shown that a combination of Taxotere, doxorubicin, and cyclophosphomide (TAC regimen) is more effec- tive than the standard FAC (5-fluorouracil, doxorubicin, cyclophosphomide) regimen in adjuvant chemotherapy of operable breast cancer (BC) with mestastases to regional lymph nodes. With higher efficacy, TAC regimen was more toxic: the incidence of febrile neu- tropenia was 24.7%. According to the current EORTC and ASCO guidelines, the use of granulocyte colony-stimulating factors (G-CSF) for primary prophylaxis is indicated when the risk of febrile neutropenia is ≥20%. This study was designed to evaluate the safety of TAC regimen with G-CSF primary prophylaxis in adjuvant chemotherapy (CT) of BC .Patients with operable BC (T1—3N1M0) and Karnofsky performance status 80% received adjuvant TAC regimen after radical surgery: Taxotere 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphomide 500 mg/m2. G-CSFs were administered in the standard doses for 5—7 days starting from cycle 1 of CT, for primary prophylaxis of febrile neutropenia.One hundred and one patients have been treated since 2006. Mean age was 47.5 years (range 25—67 years). Almost half (48.5%) of the patients had Stage IIIa disease, Stages IIa and IIb had 18.8 and 27.7% of patients, respectively.The tumor was estrogen receptor-positive in 57.4% of the patients and progesterone receptor-positive in 62.4%. Overexpression of Her- 2/neu receptor was documented in 49.5% of cases. The mean number of cycles per patient was 5.8. Ninety-one (90.1%) patients have received a complete course of 6 TAC cycles. The duration of prophylactic use of lenograstim or filgrastim during one CT cycle was 5.9 and 5.6 days, respectively.Episodes of febrile neutropenia were observed at 19 (3.2%) CT cycles in 9 (8.9%) patients. Neutropenic infections were recorded at 4 (0.78%) cycles in 3 (3%) patients.Thus, the use of GCSF substantially reduces the incidence of TAC-associated febrile neutropenia and infectious complications and ensures a safe and complete course of effective adjuvant CT for the vast majority (90.1%) of patients. The data presented suggest that there is a need for primary prophylaxis with G-CSF in all BC patients receiving adjuvant TAC.

The paper gives recent data on the use of target agents, such as erlotinib, gefitinib, cetuximab, bevacizumab, and sorafinib in advanced cancer of the cervix uteri (CCI). Approaches using target drugs in combination with chemotherapy are of the greatest interest. A spec- trum of molecular biomarkers (epidermal and vascular growth factors) in CCI and its correlation with prognosis and treatment response are shown. A number of adverse relations caused by target agents are considered.

The paper characterizes paranoic hypochondriacal development, that is comparable with expan-sive paranoia, in patients with a >5-year history of malignancies at examination. A study sample comprised 8 treated out- and inpatients (mean age 55.7±7.02 years) diagnosed as having repro-ductive organ malignancies. Their examination was made by the clinical catamnestic technique. Psychopathological disorders in the described cases of expansive paranoia are associated with the development of abnormal querulant activity that is aimed at having the medical care volume inadequate to the somatic status of patients with malignancies.The described variant of development of paranoid disorders enables their determination within the framework of cancer-induced chang- es in personality disorders with the formation and further reinforcement of the psychopathological manifestations of mainly the hy- poparanoia type. The constitutional predictors of hypochondriacal development via expansive paranoia type, which include not only certain types of personality disorders (paranoic, 50%; schizoid–expansive pole, 12.5%; icteric, 37.5%; sensitive, 12.5%), but also ac- centuations (segmental depersonalization accentuation) against which the study reactions manifest themselves as a continuation of but ab-normally transformed constitutional properties.

Objective: to improve the results of neoadjuvant chemotherapy (CT) in patients with locally advanced (L A) inoperable breast cancer (BC) at baseline, by using the intensified combination CT at the interval being reduced between the administration of cytostatic dru gs to 2 weeks to give a chance to the patients to be surgically treated.Subjects and methods. The study enrolled 26 patients aged 33 to 75 years with L A BC. Paclitaxel was administered intravenously (IV) over 3 hours at a dose of 175 mg/m2 on day 1, followed by gemcitabine, 2000 mg/m2, given by 30-minute IV infusion on day 1 every 2 w eeks. If the cytostatics were well tolerated and their effect increased, the treatment was continued up to 6 courses.Results. Eighteen (69.2%) out of the 26 patients achieved the objective effect of treatment; of them 17 (65.4%) had a partial remission and 1 (3.8) had a complete remission.The therapeutic pathomorphism of a tumor w as rated in 22 patients; fourth-degree tumor pathomorphism w as found in 2 (9%) patien ts. The follow-up of patients w as 11 to 28 months (median, 20 months). The median time to progression w as not reached in the entire group of patients.Conclusion. A combination of paclitaxel and gemcitabine in intensive dose-dense scheduling has a marked antitumor activity in BC andis characterized by its good tolerability without a pronounced myelosuppressive effect. This therapy regimen may be used as neoadjuvant CT.

The tolerability and efficiency of peritonectomy in combination with hyperthermic intraperitoneal chemoperfusion were studied in patients with pseudomyxoma peritonei. Data from 10 patients were analyzed. The pattern of complications classified as surgical and chemotherapy- associated ones is presented. The long-term results of treatment are demonstrated.

The developed chemotherapy (CT) regimen with paclitaxel and gemcitabine with the interval being reduced between the cycles up to 2 weeks can shorten the time of preoperative treatment 1.5-fold and may be further investigated in the neoadjuvant CT for inoperable breast cancer. Intensified CT in the regimen of paclitaxel 175 mg/m2 one day, gemcitabine 2000 mg/m2 one day, docetaxel 70 mg/m2 one day + doxorubi- cin 60 mg/m2 one day + colony-stimulating factors every 2 weeks has a high clinical effectiveness and a satisfactory tolerability.

The main tasks of the study were to evaluate the efficiency of treatment and to estimate time to progression and survival rates in patients with recurrent glioblastomas receiving combination treatment with irinotecan and bevacizumab. Five (41.7 %) patients achieved partial regression; disease stabilization and progression were observed in 5 (41.7 %) and 2 (16.6 %) cases, respectively. The median time to disease progression was 5.5 months; 6-month and one-year survival rates were 66.6 and 25 %. The median overall survival was 9.0 months. Treatment tolerability was satisfactory. Thus, the preliminary results of our study show the high efficiency of a combination therapy regimen incorporating bevacizumab and irinotecan for patients with recurrent glioblastomas and they are comparable with the data available in the literature on investigations of the efficiency of this treatment regimen. This study is being continued.

Since 2006, the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, has been conducting an investigation of the efficiency of targeted therapy with gefitinib in patients with brain metastasis from non-small cell lung carcinoma (NSCLC). The evaluation of treatment efficiency in 9 patients with tumor EGFR mutation in NSCLC revealed that 1 (11.1 %) and 5 (55.6 %) patients achieved complete and partial regression, respectively; disease stabilization was observed in 3 (33.3 %). The median time to progression was 7 months; the patients did not achieve the median survival. The evaluation of treatment efficiency in a group of 6 patients without tumor EGFR mutation or its evidence showed complete and partial tumor regressions; disease stabilization was noted in 3 (50.0 %); disease progression was in 3 (50 %). The median time to progression was 2 months; the median survival was 5 months. Thus, the high efficiency of treatment with the EGFR inhibitor gefitinib in patients with brain metastases from NSCLS was achieved only in a group of patients with found ECFR mutations in exons 18–21 in the tumor. Determination of the status of ECFR in the tumor is the most important prognostic factor when using therapy with the EGFR tyrosine kinase inhibitor gefitinib in patients with brain metastases. The investigation is being continued.

A combination of etoposide, doxorubicin and cisplatin plus mitotane (EPD-M) is the most effective regimen in patients with advanced adrenocortical carcinoma (ACC). Because in the Russian Federation mitotane is not registered, there are no publications about the effectiveness of EPD-M in the Russian patients. In the chemotherapy department of the NMITS of oncology named N.N.Blokhin of the Ministry of Health we conducted a retrospective analysis of the efficacy and tolerability of the EDP-M regimen as a first-line treatment in advanced ACC. We enrolled 24 patients with histologically confirmed ACC. Evaluation of the treatment effectiveness and toxicity was possible in 23 patients. Six patients (26%; 95% CI 8-44%) achieved a partial response, disease control rate was observed in 14 patients (61%; 95% CI 41-81%). Median time to progression was 4.9 months. Three patients (12.5%) were performed a radical surgical resection of residual disease after 6 cycles of chemotherapy. Then patients continued mitotane monotherapy after surgical resection. Treatment was well tolerated, with grade III and IV toxicities consisting of neutropenia in 8 (33%) patients, anemia in 1 (4%) patient, asthenia in 3 (12.5%) patients. The central neurotoxicity associated with mitotane, was observed in 2 (8.3%) patients. The EDP-M regimen is a well-tolerated and active regimen in patients with advanced ACC.

It is still unknown whether the combination of IFN-α with octreotide has benefit compared with IFN-α alone. We compared efficacy and toxicyty of IFN-α and IFN-α plus octreotide in first line of therapy of patients with NETs. There was trend to longer TTP in lung NETs pts comparing with GEP NETs pts treated with IFN-α. IFN-α may be a therapy of choice in pts with well differentiated lung NETs as first line treatment. IFN-α have a similar toxicity profile comparing with IFN-α combined with octreotide.

The meeting of experts, concerning the treatment of thyroid cancer was held in Moscow in June 2016. The aim of the meeting was unsolved tasks in the field of therapy of the patients with radioactive iodine-refractory differentiated thyroid cancer. Nowadays, this group of patients still has a poor prognosis with respect to life expectancy. The experts are faced with some difficulties in choosing the treatment tactics in patients after radioiodine therapy have become ineffective and we observe disease progression. And still valid questions remain unsolved: when should doctors stop therapy using radioactive iodine? When should patient start therapy using targeted agents? What kind of targeted agent should specialist choose for treatment of this desiase? How should one manage the developing side effects against the backdrop of targeted therapy? These and some other problems have been discussed within the framework of this counsel.

The article shows the experience of eribulin application in actual clinical practice in Oncology institutions of the Russian Federation concerning metastatic breast cancer. We have analyzed the efficacy of the drug in case of different subtypes of the tumor and have chosen patients, depending on the location of metastases and with proven maximum efficacy of eribulin. We have shown the side reactions and the possibility of application of eribulin in combination with other antineoplastic agents.

In recent years, the main scientific directions concerning ovarian cancer have been associated with the attempt to individualize the treatment based on prognostic and predictive molecular biological markers. The damage in BRCA1 and BRCA2 genes is identified in 10-15% of ovarian cancer cases. The main function of BRCA proteins is responsibility for repairing double-strand break in DNA by a mechanism of homologous recombination. The result of BRCA gene dysfunction is BRCA-associated DNA damage repair mechanism. As a result, these tumors can be extremely sensitive to DNA-damaging cytostatic agents - such as platinum-based drugs. Several studies show the better survival rates of patients with BRCA mutations in comparison with sporadic ovarian cancer. The information concerning the course of disease and treatment characteristics of patients with ovarian cancer associated with BRCA1, 2 mutations in the Russian population of patients is extremely limited.

Somatostatin analogs plays a key role in the treatment of disseminated well-differentiated functioning and nonfunctioning neuroendocrine tumors (NET). Its ingibit hormonal activity of NET by binding to somatostatin receptors, have antiproliferative effect, increase the median time to progression. Approximately 10% of patients have significant side-effects when used octreotide. Octreotide and lanreotide differ in structure. Intolerance to one drug, it may be assigned to another.

Colorectal cancer (CRC) is ranked third in the world among malignant tumors in morbidity - more than 1.3 million (1 360 000 in 2012) new cases per year, and fourth in mortality - 694 000 deaths in 2012. CRC medicamentary is very important in case of this disease, and have been applying as in case of adjuvant treatment schemas and in case of metastatic disease treatment. All this allowed us significantly improve the life expectancy of the patients last decade. One of the last achievements in modern drug therapy of metastatic CRC (mCRC) is the existence of new drug - regorafenib. Regorafenib is a multi-kinase inhibitor, blocking VEGFR 1-3 and TIE-2 protein kinases, involving in tumor angiogenesis and inhibiting the growth of new blood vessels. The drug also inhibits oncogenic protein kinases: KIT, RET and RAF-1, BRAF and mutated BRAFV600E which are involved in cell proliferation and survival of cancer cells and effects on platelet-derived growth factor receptors (PDGF-R) and fibroblast growth factor receptor (FGFR) affecting the microenvironment tumor. The results of Phase III CORRECT study concerning regorafenib show the desirability of using the regorafenib as a new therapeutic option for patients with mCRC, previously have been treated for many times and have exhausted all the possibilities of drug therapy.

Everolimus is the targeted drug approved for the treatment of neuroendocrine tumors (NET). Efficacy of everolimus in combination with octreotide-depo has been shown in Radiant-2 randomized trial in patients with well-differentiated NET in different locations. Everolimus as monotherapy versus placebo was studied in patients with pancreatic NET in the framework of Radiant-3 randomized trial, where the statistically significant advantage of everolimus was proved. The article presents the experience of targeted therapy in 33 patients with highly-differentiated NET in different locations, and some aspects of everolimus use are analyzed. Efficacy, toxicity and long-term results of therapy are evaluated. Everolimus has demonstrated its efficacy in the unfavorable group of patients, most of whom were heavily pretreated with multiple courses of chemo - and biotherapy. Tumor growth control was 79%. Toxic complications were adequately managed by dose reduction of the drug without compromising its effectiveness. Moreover, clinically significant toxicity appeared an efficacy predictor as complicated cases showed twofold increase in median disease-free survival. Preliminary data suggest that therapy with everolimus is preferable at the first stages of treatment of NET.

Avastin (bevacizumab) is a humanized monoclonal antibody with evident antiangiogenic activity, which blocks vessel endothelial growth factor (VEGF) and prevent its binding with receptors. Chronologically Avastin was among the first (second after trastuzumab) targeted agents approved for clinical practice. Also it is the only targeted agent used in the main malignant solid tumor types: metastatic colorectal cancer, locally recurrent or metastatic breast cancer, metastatic or recurrent nonsquamous non-small cell lung cancer, advanced and/or metastatic renal cell cancer, glioblastoma (stage IV glioma according to WHO classification) and epithelial ovarian, fallopian tube, or primary peritoneal cancer. Therefore Avastin can be defined today as the first and the best, because not one targeted agent has so wide clinical use and indications in practical oncology and moreover practically there were no ineffective clinical trials with Avastin. Also it is necessary to mention that large clinical experience with Avastin demonstrates comparative safety of the agent in different patient’s subgroups and populations.

Dynamic of biochemical markers of neuroendocrine tumors (chromogranin A, serotonin, 5-hydroxyindoleacetic acid) are predictive factorsof biotherapy efficacy. We found that 30% decreasing of biochemical markers within 6 months improves median of time to progression for patients with neuroendocrine tumors.

Statement of hormonal activity and potential malignancy are the most important issues of diagnosis and selection of appropriate treatment way for patients with adrenal tumors. Adrenal cortical carcinoma (ACC) is rare disease with poor prognosis. Incidience of ACC is about 0.5-2 per million, and no more then 2-4% among adrenal tumors. This draft of guidelines of diagnosis and treatment of ACC is offered to common discussion among wide round of specialists.