Non-small cell lung cancer (NSCLC) is the leading cause of death from cancer worldwide. Despite the success over recent years in the treatment of NSCLC it has not yet been able to achieve good long-term survival. The development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers, including non-small cell lung cancer (NSCLC). Nivolumab is the PD-1 inhibitor approved for the treatment of NSCLC to show a survival benefit in a randomised phase III trials. The experience of physicians in routine clinical practice is often different from those in a controlled clinical trial setting. The purpose of this analysis is to evaluate nivolumab use in real world setting. Results: The general survival at 76 patients by metastatic NSLC receiving an immunotherapy nivolumab during the period from 2015 to 2019 is analysed. The minimum time of observation was 1.6 months. The median of the general survival made 7.6 months (5.92-9.41. DI 95%). The one-year survival - 35%, at the same time 3-year survival was 25%. At patients with the objective answer the median of the general survival was not reached. Immunomediated adverse events developed in 42% of patients, but only 6.6% showed the development of adverse events of 3-4 degrees, which indicates a favorable toxicity profile. Conclusion: the results received by us correlate with data of clinical trials.

Nowadays neoadjuvant immunotherapy is one of the main research areas in oncology. This interest is supported by the success of check-point inhibitors in treatment of advanced and metastatic lung cancer. The postulate that neoadjuvant immunotherapy achieves tumor devitalization before surgery is confirmed by a morphological assessment of surgical material with a gradation of the antitumor effect. In addition to affecting directly to the tumor, it also affects at potential micrometastases. A morphological assessment  with a gradation of the antitumor effect (MPR – a major pathomorphological response, CPR – a complete pathomorphological response) provides a unique opportunity to identify predictors of effectiveness and adjust the treatment tactic. A major morphological response (MPR – less than 10% of viable tumor cells in the tumor tissue) is associated with better overall survival. Currently, there is evidence that the appointment of neoadjuvant immunotherapy in mono mode allows you to achieve MPR in 18–45%, and the use of a combination of immunotherapy with chemotherapy increases it to 32–92%. Neoadjuvant immunotherapy or combination with chemotherapy does not postpone surgical treatment but allows us to achieve the better result.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with unmet needs of effective medications. Lenvatinib – a new oral multikinase inhibitor (MKI) proved to be as effective as sorafenib in terms of survival has been added recently to standard first-line treatment of advanced HCC. Regorafenib, another MKI in the RESORCE trial, a phase 3 study evaluating regorafenib in HCC patients who experience disease progression after first-line treatment with sorafenib, have shown a 2.8-month median survival benefit over placebo (10.6 versus 7.8 months). Cabozantinib and ramucirumab have all been shown to extend overall patient survival in sorafenib-refractory HCC patients and appear to have a reasonable safety profile. Immune checkpoint inhibitors therapy with nivolumab or pembrolizumab – monoclonal antibody to PD1-receptor are effective in about 15–18% of HСС patients presenting with long-lasting objective responses. Immunotherapy was safe in terms of viral hepatitis activation, but in comparative trials in first and second-line settings failed to achieve statistical difference in overall survival other sorafenib and placebo, respectively. Due to less toxic profile HCC immunotherapy seems to be a reasonable option to Child-Pugh B patients. Multiple ongoing trials are studying immune checkpoint inhibition alone or in combination with TKIs. The results of these trials will help determine the optimal choice, timing, and sequence of agents. This article reviews current situation in the field of new therapies of HCC from the point of common medical practice in searching for optimal second-line treatment decision in different clinical situations.

Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase domain, which has shown effectiveness in the treatment of non-small cell lung cancer with activating EGFR mutation. A number of large randomized studies have shown a significant increase in survival without progression in the use of erlotinib and other tyrosine kinase inhibitors in comparison with standard chemotherapy. At the same time, there were no differences in the overall survival rate, which is due to the high frequency of tyrosine kinase inhibitors use in subsequent therapy lines in patients who had progression during the first-line chemotherapy. At the same time, this retrospective study showed an obvious (more than doubling) increase in the overall survival rate of patients receiving treatment with tyrosine kinase inhibitors as compared to historical control. There were no significant differences between the first and second generation tyrosine kinase inhibitors. Mutation of T790M is one of the main mechanisms of resistance to erlotinib. When progressing against the background of erlotinib treatment, the third generation tyrosine kinase inhibitor osimertinib is effective in case of T790M mutation detection. The combination of erlotinib with bevacizumab leads to an increase in survival without progression, without affecting the overall survival rate. The combined use of chemotherapy and tyrosine kinase inhibitors requires further study. An example of a long-term effect on the background of erlotinib treatment in a patient with non-small-cell lung cancer of stage IV with EGFR mutation is given. The  total duration of treatment was 68 months, including the therapy with erlotinib in combination with bevacizumab and local radiation therapy on the progression zone (rib metastasis), which lasted for 21 months against the background of the indolent course of the disease.

Up until recently, neoadjuvant and adjuvant treatment regimens for breast cancer (BC) were considered equivalent in their effect on long-term treatment outcomes. Despite the fact that additional information on the prognosis of patients (achievement or failure to achieve complete drug pathomorphosis) was obtained during neoadjuvant therapy, we could not change this prognosis, since there was no evidence that any variant of adjuvant therapy could improve survival of patients, who did not achieve complete morphological tumour regression. In December 2018, investigators presented the results of the first planned interim analysis of invasive disease-free survival (iDFS) of patients with early HER2-positive breast cancer, who had residual tumour after neoadjuvant anti-HER2-containing therapy, depending on the adjuvant treatment option: either trastuzumab emtansine (n = 743) or trastuzumab (n = 743). The expected 3-year iDFS in patients, who received trastuzumab emtansine as adjuvant therapy, was 88.3%, while that in the standard trastuzumab group accounted for only 77% (RR = 0.50; 95% CI 0.39–0, 64; h <0.001). The results of the KATHERINE study, which showed an improvement in the survival rates of patients with HER2-positive breast cancer, who did not achieve complete therapeutic pathomorphism (pCR) against the background of neoadjuvant anti-HER2 therapy with the use of trastuzumab emtansine in the adjuvant mode, are not just an important milestone in the treatment of HER2-positive breast cancer. These results reverse the attitude towards neoadjuvant therapy, as we were able, for the first time, to improve the treatment outcome due to the change of the therapy based on therapeutic pathomorphosis data. Thus, this approach leads to the fact that neoadjuvant therapy becomes a more effective technique, at least in HER2-positive breast cancer.

Molecularly targeted therapy with tyrosine kinase inhibitors (TKI) has been recognized as the optimal treatment option for patients with EGFR-positive non-small-cell lung cancer (NSCLC). At present, 5 drugs of this group are available: first generation – erlotinib and gefitinib, second generation – afatinib and dacomitinib (not registered in Russia), and third generation – osimertinib. The drugs have some peculiarities, this refers to their antitumor activity, safety profile, and resistance mechanisms. Knowledge of these differences is necessary to determine a rational treatment plan. Gefitinib and erlotinib increase the time before progression compared to standard chemotherapy, but do not affect the overall survival rate. Afatinib significantly increases the time before progression, and in the cohort of patients with deletion in the 19th exon – the overall survival rate. Dacomitinib was more effective than gefitinib in terms of time before progression and total survival. On average, the disease progresses after a year and a half of successful treatment. The dominant mechanism of resistance development to TKI of the first and second generation consists in accumulation of mutation of the gatekeeper gene T790M. Most often it is determined in patients with deletion in the 19th exon (Del19). Osimertinib has proved to be effective against tumors not only with activating mutations, but also with T790M resistance mutation, and with minimal activity to EGFR «wild» type receptors. The first indication that it was registered was progression on targeted therapy with first and second generation drugs caused by the secondary mutation of T790M. Later, the advantage of osimertinib compared to gefitinib/erlotinib in untreated EGFR-positive patients was proved. Thus, there are at least two main options for treatment tactics: the consistent use of second and third generation drugs or prescription of osimertinib in the first line with subsequent chemotherapy. Evaluation and consideration of known prognostic factors will allow choosing the optimal tactics for a particular patient.

Background. Metastatic breast cancer is still an incurable disease, and is currently regarded as a chronic process requiring longterm treatment with periodic therapy replacements. Hormonal therapy shows its therapeutic efficacy with less toxicity and a better quality of life for patients compared with chemotherapy and is one of the main treatment for patients with luminal subtypes of breast cancer.
The purpose of the study was to assess the efficacy and toxicity of fulvestrant in treatment for metastatic breast cancer.
Material and methods. The study included patients with metastatic breast cancer with positive hormonal status developing progression after adjuvant treatment or chemotherapy or hormonal therapy due to metastatic cancer, ECOG≤2, with normal liver, kidney and marrow function. Fulvestrant was administered intramuscularly 500 mg once a month with a loading dose 500 mg on day 14 of the first month. The effect was evaluated every 3 months.
Results. We analyzed the efficacy and safety of fulvestrant in second-line and over treatment of 20 patients with metastatic breast cancer. Overall response was 65% (13 patients), including partial remission (PR) in 2 (10%) and stabilization in 11 (55%) patients. Progression was found in 7 (35%) patients. The median of relapse-free survival was 6 month. 1-year overall event-free survival was 45%. The median of overall survival was not reached due to the short observation period. 1-year overall survival was 70%. Adverse events in our group of patients included asthenia (80%), hot flushes (25%), headache and nausea (20%).
Conclusions. The efficacy of fulvestrant in patients with metastatic breast cancer was high enough and did not depend on the previous treatment, with a favorable toxicity profile.

Interview with Irina A. Korolevа, Dr. of Sci. (Med.), Professor of Chair for Clinical Medicine, Postgraduate Education, Reaviz Medical University Samara, Russia) (oncology)

Metastatic triple negative breast cancer is considered to be a chemosensitive malignancy especially in treatment-naïve setting. However, tumor cells are able to develop various mechanisms of drug resistance and eventually they become insusceptible for common cytostatic agents. Expansion of treatment-resistant tumor cells represents significant therapeutic challenge and this leads to unfavorable prognosis of advanced triple negative breast cancer. Backbone of treatment for patients with this disease is sequential treatment with various cytostatic drugs with non-cross resistant mechanisms of action, however even with the stateof-art therapy median overall survival does not exceed 15 months. The integration of novel epothilone analogue ixabepilone into clinical practice appears to be a promising strategy for the treatment of advanced pretreated triple-negative breast cancer, especially for patients who are resistant to taxanes and anthracyclines. Combination of ixabepilone with capecitabine is superior to capecitabine monotherapy in terms of response rate (34.7% vs 14.3% with capecitabine monotherapy) and median progressionfree  survival (5.8 months vs 4.2 months). At the same time ixabepilone has favorable safety profile and manageable toxicity, 67% developed peripheral neuropathy which is comparable to neuropathy rate with other microtubule inhibitors such as taxanes and eribuline. Here we describe a clinical case of patient with heavily pretreated metastatic triple negative breast cancer resistant to taxanes, anthracyclines and eribuline who was successfully treated with ixabepilone and capecitabine combination.

Introduction. The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods. The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results. 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4),  the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings. The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

The relevance of the study is conditioned by the growth of breast cancer (BC) incidence in the population and the need to identify psychosocial factors that cause inappropriate behavior of patients. The authors try to understand the reasons for this behavior (late access to medical care, patients’ lack of recognition of signs of relapse). The aim of the study is to find out how the level of awareness of breast cancer patients of the disease mediates their sensual perception of the disease, their understanding of symptoms, and their behavior. Materials and methods: 38 women with breast cancer of stage I–III of the Department of Thoracic Surgery and Chemotherapy of M.F. Vladimirsky Moscow Regional Research and Clinical Institute participated in the study. Semistructured clinical interviews were conducted to identify patient perceptions of the disease, treatment, and behavioral strategies. Sensory perception of the disease, understanding and categorization of its manifestations were studied with the help of the modified test «Choice of descriptors of intraceptual sensations» developed by Tkhostov and Elshanskiy in 2003. As a result of the interview the patients were divided into 3 subgroups: with full awareness of the fact of the disease, partial and its absence. Patients with full awareness are characterized by the presence of clearly localized bodily sensations and diffuse, generalized markers of general painful condition (described by means of feelings). Patients consider anxiety and depression to be symptoms of cancer, and therefore probably expect to get rid of them as a result of basic therapy (which is impossible). Patients with partial awareness of the disease mix the physical symptoms of the cancer with those of the comorbid disease (which are considered to be the main one), do not recognize the dangerous sensations, underestimate their significance and, consequently, may miss the onset of a relapse. Patients with a lack of awareness of the disease do not know what to navigate by, underestimate dangerous sensations (e.g. pain), overestimate the importance of the sensations associated with the operation (e.g. numbness), but their physical experience of the disease is similar to that of patients with full awareness, and the declared anozognosis is psychologically protective. Patients need explanatory work on differentiation of physical experience of the disease, determination of marker sensations requiring medical assistance and formation of motivation for further (postoperative) therapy.

Introduction. Colorectal cancer (CRC) holds leading positions in the cancer incidence and mortality patterns worldwide. In this regard, the study of new effective drugs and development of new treatment regimens for advanced CRC is receiving priority attention today.
Objective of the study: develop a new 3-component chemotherapy (CT) regimen based on the combination of oxaliplatin (oxa)/irinotecan (iri)/tegafur (Ftorafur®) ± Leucovorin, study its efficacy and safety in the first-line therapy for advanced CRC; assess the feasibility of its use in the outpatient setting.
Materials and methods. The study included patients with advanced CRC, who had not previously received drug therapy for disseminated disease. In this study, all patients received first-line CT therapy based on a combination of: oxa/iri/tegafur (Ftorafur®) ± Leucovorin. The researchers developed and studied 2 CT regimens. CT regimen in subgroup I: iri (150 mg/m2 BSA intravenous (IV) infusion, 90-minute infusion, Day 1) + oxa (100 mg/m2 BSA IV infusion, 2-hour infusion, Day 1) + tegafur (Ftorafur ®) (1200 mg (400 mg TID), per os, daily, Days 1–14) + Leucovorin 50 mg TID, 15–20 minutes before taking tegafur, daily, Days 1–14. The next course starts from Day 22. CT regimen in subgroup II: iri (150 mg/m2 BSA intravenous (IV) infusion, 90-minute infusion, Days 1 and 15) + oxa (100 mg/m2 BSA IV infusion, 2-hour infusion, Days 1 and 15) + tegafur (Ftorafur®) (1200 mg (400 mg TID), per os, daily, Days 1–14). The interval between the courses is 14 days. The next course starts from Day 29. The researchers assessed the immediate and long-term results of treatment and safety of two above-mentioned first-line therapy chemotherapy regimens for advanced CRC.
Results. The study included 30 patients with advanced CRC, 6 of whom received 3-week СТ regimen (subgroup I), 24 patients received 2-week regimen (subgroup II). In subgroup I, 4 (66.7%) patients achieved partial regression (PR) of metastases, 2 (33.3%) patients achieved long-term stable disease (SD ≥ 6 months). Thus, the disease control (PR + SD ≥6 months) was achieved in 100% of cases. The median progression-free survival (PFS) in this subgroup was 9.53 months; the median overall survival (OS) was 13.60 months. In subgroup II, PR was reported in 13/23 (56.5%) patients, of which 4 (17.4%) were radically operated. SD ≥6 months was achieved in 6 (26.1%) patients. Thus, the disease control (PR + SD ≥6 months) was achieved in 82.6% of cases. The median progression-free survival (PFS) in this subgroup was 8.73 months; the median overall survival (OS) was 17.24 months. In the general group of patients, who received therapy regimens I and II, the disease control was 86.2% (PR-58.6%; SD ≥6 months was 27.6%); median PFS was 9.57 months; median OS was 16.8 months. Conclusions. Data resulting from our study suggest that the combination of oxa, iri, and tegafur (Ftorafur®) ± Leucovorin is effective and safe 3-component first-line CT regimen for advanced CRC, which is easy for use in outpatient setting.

Introduction: Ramucirumab (Ram), a human IgG 1 antibody against vascular endothelial growth factor receptor 2. This multicenter retrospective study aims to reviewed the results of Ram-based therapy as second-line treatment in patients with advanced gastric cancer in a real-life setting.Methods: it was an observational, retrospective study carried out in 11 Russian hospitals. Endpoints included safety, overall survival (OS), progression-free survival (PFS), objective response rate (ORR).Results: 163 patients were included. Ram was used as the second- line in 166 combined with weekly paclitaxel (PTX) in 104 patients or irinotecan-based chemotherapy (mostly FOLFIRI) in 42 patients and as monotherapy in 17 patient. In second line VEGF-related toxicity (all grades) included epistaxis (39,2%), proteinuria >1g/day (4.9%), and arterial hypertension (68%); grade 3-4 toxicity was bleeding (4.3%), perforation (2,4%), venous thrombosis (6,13%) and brain ischemia (0.6%, grade 5). 15 patients (9,2%) discontinued therapy due to toxicity.
Conclusion: These real-life efficacy data of ramucirumab are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.

The article describes a rare clinical case. Progression of the disease in the form of multiple metastases to the liver, lymph nodes of the hepatoduodenal ligament and retroperitoneal region was detected in a 33-year-old patient with G2 pancreatic neuroendocrine tumour (NET) 1.5 months after surgical treatment. The patient received targeted therapy with sunitinib, oral protein kinase inhibitor, at daily dose of 37.5 mg and biotherapy with lanreotide, an analogue of somatostatin, which is used as a monthly subcutaneous injection. A partial effect in the form of reduction of all previously identified metastatic foci was reported after 12 months of treatment. Magnetic resonance imaging (MRI) showed a full therapeutic effect after 17 months of co-use of two drugs. So far, the patient continues to receive treatment for 25 months. Complete resolution of metastatic lesions persists for 8 months. The article shows the possibility of increasing anti-tumour efficacy in using targeted therapy combined with somatostatin analogues. The combined use of sunitinib and lanreotide has a pronounced anti-tumour effect in the first line therapy for highly differentiated pancreatic NEO and is tolerated without significant toxicity. With long-term treatment, the ease of use and availability of the required dosage of Sunitinib-Nativ oral preparation and ready-to-use injection depot makes it possible to maintain a regular lifestyle, professional activity and do not affect significantly the patients’ quality of life. It is necessary to continue the study of this first-line therapy regimen for pancreatic NET under clinical protocols.

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.

Current landscape of personalized and molecular-driven approach to cancer treatment contributes to a rapid growth of novel biomarkers used for a targeted therapy. Amplification or over-expression of HER2 has been shown to play an important role in the development and progression of some cancers. Recent studies have shown that over-expression of HER2 is found in up to 5% of colorectal cancers (CRC). These findings led to active research of therapeutic use of HER2-targeted therapy in a subset of patients with metastatic CRC, especially in patients with wild-type RAS, who progressed on anti-EGFR targeted therapy. According to data from several published studies, the rate of objective responses, progression-free and overall survival in this subset of patients matches or exceeds same rates that are achieved while using BRAF-targeted therapies in BRAF-mutated metastatic CRC patients and immunotherapy used in subjects diagnosed with MSI-H tumors. Currently, there is no conclusive data on potential of HER2-targeted therapy in RAS-mutated CRC patients. In this paper, we report a case of durable objective response obtained on trastuzumab therapy in patient with metastatic CRC, mutation in 12th exon of KRAS gene and over-expression of HER2 in 40% of tumor cells, after progression on several lines of chemotherapy and anti-angiogenic targeted therapy.

For a long time, the standards of first-line drug therapy for patients with advanced non-small-cell lung cancer (NSCLC), excluding cases of mutations of EGFR, ALK and ROS1, were platinum-containing regimens. However, the chemotherapeutic regimes used in the therapy of the first line therapy of NSCLC have insignificant efficiency, and therefore the total survival rate of patients remains low: the response rate varies from 12 to 37%, the median survival rate without progression is from 4 to 7 months, the median of total survival – from 8 to 13 months.
The use of a new class of immunooncologic drugs called immune checkpoint inhibitors has expanded the treatment options for NSCLC patients. One of the most effective immunooncologic drugs is pembrolizumab, which showed a clear advantage in increasing the overall survival rate in comparison with chemotherapy – median was 30.0 months vs. 14.2 months. (RR 0,63; 95% CI: 0,47–0,86; р = 0,002).
The article presents the clinical observation of a patient with the diagnosis of «adenocarcinoma of the upper part of the right lung of the IIIA stage» with the progression developed in two years after the combined treatment. The patient received 29 courses of pembrolizumab immunotherapy in the first line of therapy with partial response achievement.
The presented clinical observation confirms the efficacy of pembrolizumab in the first line of NSCLC treatment. Due to the immunotherapy with pembrolizumab there is no progression of the disease during more than 22 months with satisfactory quality of life and absence of pronounced toxicity of treatment.

The standard of treatment of the second line of disseminated stomach cancer is palliative chemotherapy with paclitaxel in combination with ramucirumab. Vascular endothelial growth factor A (VEGF-A) is a key regulator of blood vessel growth and its connection to the corresponding receptors of VEGFR1/2 leads to the activation of neoangiogenesis. In patients with disseminated stomach cancer, the level of VEGF-A rs25648 has a negative impact on both survival without progression of the disease and on overall survival. The antitumor activity of neoangiogenesis inhibitors in the second line of treatment may be related to a higher concentration of VEGF-A, the level of which, in turn, correlates with the volume of tumor tissue. In a small study of the second phase, the addition of bevacizumab to docetaxel in the second line of treatment of patients with disseminated stomach cancer allowed to achieve tumor growth control in 48% of patients. Meta-analysis of 7 studies (n = 905) showed that the use of two-component modes based on irinotecan in the second line in comparison with irinotecan monotherapy allows to increase significantly the survival rate without progression. This clinical observation illustrates this approach. Patients with signet-ring cell disseminated stomach cancer after rapid progression on the background of the first line of chemotherapy with docetaxel, oxaliplatin and 5-fluorouracil were prescribed chemotherapy of the second line in combination with bevacizumab. It is the second line of treatment that allowed to achieve long-term control of the disease, equal to 18 months, with a life expectancy of 30 months. When analyzing a clinical case, the justification of the patient’s treatment tactics, the choice of two-component mode of chemotherapy and the use of bevacizumab was carried out.

Ovarian cancer ranks first in the mortality causes pattern of female reproductive cancers in Russia. Treatment of relapsed ovarian cancer remains a significant challenge to practicing oncologists. Introduction of PARP inhibitors in clinical practice are the most significant achievements in this area. The use of drugs of this class significantly reduced the relative risk of tumour progression in relapsed ovarian cancer and increased the relapse-free duration. At the same time, many issues related to the practical use of PARP inhibitors remain unresolved. This review presents practical approaches to determining the categories of patients, who receive the greatest benefit from the use of drugs of this class. The article addresses epidemiology of BRCA-associated ovarian cancer. The authors presented information on modern methods for genetic testing, classification of mutations depending on proposed class of pathogenicity, and reviews the problems associated with identification of «variants of unknown clinical relevance». The mechanisms of action of PARP inhibitor are described in detail here. The evidence base demonstrating the efficacy and safety of olaparib, the only PARP inhibitor approved for clinical use in the Russian Federation as supportive therapy for platinum-sensitive relapsed BRCA-associated ovarian cancer, is discussed. The article detailed information on the spectrum of potential toxicity that is most commonly faced by oncologists prescribing olaparib and other PARP inhibitors. The main aspects of management of adverse events during olaparib therapy are also presented.

Ovarian cancer is the fifth leading cause of cancer-related death among women in the world. In spite of recent progress in treatment strategy, around 70 % of ovarian cancer patients relapse. The cytoreductive surgery followed by platinum-, taxane-containing chemotherapy is the standard approach to the primary treatment of ovarian cancer; a variant of neoadjuvant chemotherapy with interval cytoreduction may be used in patients with stage IIIC-IV disease.
Given that angiogenesis plays a central role in progression of solid tumour growth and metastasis, recent studies have focused on anti-angiogenic treatment. Bevacizumab, a humanized IgG monoclonal antibody that inhibits the vascular endothelial growth factor receptor, is most promising antiangiogenic drug. Bevacizumab was approved on December 23, 2011 by the European Medicines Agency and on June 13, 2018 by the Food and Drug Administration as first-line treatment in epithelial ovarian, fallopian tube or primary peritoneal cancer stage III or IV in combination with carboplatin and paclitaxel. Based on sub-analyses, the recommended dosage of bevacizumab is 15 mg/kg every 3 weeks for a total of 22 cycles. Bevacizumab is a well-studied drug with a favourable safety profile that has been used in routine clinical practice for more than 10 years. However, the search for predictors to identify the category of patients, who will benefit most from bevacizumab therapy, is still in progress, and clinical trials that may improve the therapeutic potential in treating ovarian cancer in the near future due to introduction of new combinations of bevacizumab with PARP inhibitors and immuno-oncological drugs are under way. In view of acquisition of mature clinical trial data, a range of the most discussed issues regarding optimal use of bevacizumab in patients with ovarian cancer has been identified.

Aim. To evaluate impact of different clinical features on prognosis in Diffuse Large B-cell lymphoma (DLBCL) patients and to determine potential correlation between IHC markers (double-expression of c-myc, bcl-2 and p53) on unfavorable clinical characteristics in DLBCL patients.
Methods. We analyzed 215 patients with DLBCL who received treatment from 2008 to 2016. We assess impact of different clinical features, such as B-symptoms, extranodal involvement, advanced stages and refractory course on PFS. In this study we also access potentially unfavorable impact of double expression of c-myc and bcl-2 and p 53 by immunohistochemical analysis.
Results. In both uni- and multivariant analysis B-symptoms, advanced stages and primary-refractory course were identified as negative prognostic factors for PFS rates. We found tendency to correlation between double expression of c-myc and bcl-2 and high International prognostic index as well as expression of p53 and advanced stages (87,5% vs 56,4% respectively, р = 0,095).
Сonclusion. Patients with DLBCL aggressive course of the disease (B-symptoms, advanced stages and primary-refractory disease) have lower rates of PFS. Double-expression of c-myc and bcl-2 and p53 can be potentially associated with aggressive course of the disease.

Treatment of pain syndromes caused by bone metastases is a very important problem because of their prevalence in various tumor processes. The use of radiotherapy significantly alleviates pain, even in patients receiving strong opioids. However, at its initial stage, the pain may increase due to the inflammatory component. In this case, pathogenetically justified analgesics are non-steroidal anti-inflammatory drugs. It is reasonable to use them (in the absence of contraindications) in maximum doses with a subsequent gradual decrease, until complete discontinuation.

Prostate cancer is one of the most common malignant neoplasms in men. Nowadays, the overall mortality rate of this disease continues to increase, including due to the high frequency of primary detection of its widespread and metastatic forms. The effectiveness of hormone therapy of metastatic prostate cancer is limited in time, after which the disease progresses. The use of more aggressive strategies, including chemotherapy, in addition to androgenic deprivation in this category of patients may have some advantages and continues to be discussed. The article presents an overview of the results of clinical studies of docetaxel efficacy in combination with androgen-deprivational therapy in patients with oligometastatic hormone-sensitive prostate cancer. It has been determined that chemotherapy in patients with metastatic hormone-sensitive prostate cancer leads to an increase in the overall survival rate. The effectiveness of chemotherapy may depend on the amount of metastatic lesion. Although the higher efficacy of such treatment is noted in the case of a large volume of metastatic lesion, currently it is impossible to speak unequivocally about the need of adding docetaxel to the androgendeprivational therapy in patients with oligometastatic hormone-sensitive prostate cancer due to the limited statistical power of the presented data and heterogeneity of patients due to the lack of clearly defined criteria of oligometastases.
Taking into account these circumstances, future clinical studies to assess the effectiveness of chemotherapy in patients with oligometastatic hormone-sensitive prostate cancer and the analysis of their results can help to expand the boundaries of treatment strategies.

Prostate cancer is one of the most actual oncourological diseases because of the persisting high rates of morbidity and mortality from this pathology. More than 1 100 000 new cases of this pathology are registered in the world every year. The incidence of prostate cancer in the Russian Federation continues to increase steadily. Despite the success in early detection of this disease, primarily due to the introduction of diagnostics with the use of a specific prostatic antigen, the frequency of detection of primary metastatic cancer of the prostate gland remains high and is about 20%. Metastatic castration-resistant prostate cancer is an extremely heterogeneous disease with an unfavorable prognosis in most of these patients, which requires a differentiated approach when prescribing therapy in each case. Despite the standard approach to prescribing chemotherapy as one of the main methods of drug treatment, the method of hormonal therapy of the second line using drugs aimed at the androgenic mechanism of cellular proliferation regulation is an effective and less toxic option. A fundamentally different mechanism of action has a new drug hormonal therapy of the second line enzalutamide, which is able to selectively block androgen receptors and disturb the translocation of the signal from the receptor into the cell and the cell nucleus. A number of large randomized trials that studied the effectiveness of this drug have allowed to register it for clinical use, including in our country. The article presents a review of the literature on the use of enzalutamide in patients with metastatic castration-refractory prostate cancer, as well as a description of the clinical case of the use of this drug in real practice.

The article is devoted to the issue of clinical and neurological features of primary brain tumors (PBT). PBT account for 2% of the total number of human tumors. PBT represent an urgent social problem, causing disability and mortality. The incidence rate of primary tumors of the brain and other parts of the central nervous system in the United States from 2011 to 2015 amounted to 23.03 cases per 100,000 population. The most common histological types of PBT: meningioma (36.4%), pituitary tumors (15.5%)
and glioblastoma (15.1%).
The clinical picture of PBT is represented by cerebral and focal symptoms. Neurological deficit is determined by the location and volume of the neoplasm.
The initial manifestations of tumor growth may be symptoms of irritation of the squeezed area of the brain tissue, which will be replaced later by symptoms of prolapse. Cerebral symptoms in most cases are associated with increased intracranial pressure and  the development of cerebral edema. The subsequent development of the tumor process leads to the dislocation of brain structures and the formation of wedge syndromes. The most common clinical symptoms are: cognitive deficit (36%), convulsive syndrome (35%), headache (31%), ataxia (24%) and motor deficiency (22%).
The article summarizes the data of world and domestic clinical studies aimed at determining the prevailing symptoms of primary brain tumors for the purpose of early diagnosis, timely medical care and assessment of the effectiveness of the treatment. Knowing the specifics of the clinical picture will significantly increase oncological alertness, which will lead to early diagnosis and timely treatment of PBT, which play a key role in improving the quality of life and increasing its duration.