Malignant tumors of the stomach and esophagogastric junction in advanced stages progress quite aggressively, and the prospects for treatment of these patients remain unpromising. The use of checkpoint-inhibitors has proven to be an advanced treatment method for various types of cancer around the world. In theRussian Federation, nivolumab has been successfully registered as a monotherapy for common or recurrent stomach or esophagogastric junction cancer after two or more lines of systemic antitumor drug therapy. This literature review focuses on the use of registered checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab) as mono- and/or combined therapy in tumors of the stomach and esophagogastric junction, including tumors with high microsat- ellite instability (MSI-high). This review includes a description of the main therapeutic approaches using checkpoint inhibitors: prescription in mono-mode, in combination with other checkpoint inhibitors (ipilimumab) and cytotoxic drugs, and in combination with tyrosine kinase inhibitors (regorafenib). Issues of efficiency and tolerability of these combinations in patients in different therapeutic lines are considered. The role of possible predictors of therapy response is analyzed: biomarkers such as PD-Ll, MSI, dMMR and TMB expression in tumor tissues as well as immunofenotyping in fresh biopsy samples are evaluated. This article reviews and evaluates the strengths and weaknesses of checkpoint inhibitors and their possible uses.

Understanding of cancer biology is at the cornerstone of design of new and effective treatment strategies. Identification of molecular drivers of tumor growth and progression allow identify right patient for the right treatment for personalized treatment plan optimization. Breast cancer (BC) encompasses a heterogeneous collection of neoplasms with diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Molecular and histopathological classification aims to categories tumors into subgroups to inform clinical decisions, to improve long-term treatment results and maintain the quality of life of this group of patients. Germinal mutation in the BRCA1/2 (BRCAm) genes in a tumor determines the hereditary predisposition, disease manifestation, therapeutic options and clinical efficacy. Therefore, patients withBRCAmBCrepresent a special subgroup requiring personalized treatment approach.

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is a targeted therapeutic agent that acts as inhibitor of single-strand breaks reparation, leading to their accumulation, conversion to double-strand breaks and eventually to cancer cell apoptosis. Olaparib is a first-in-class PARP-inhibitor with an outstanding antineoplastic activity known for some malignant tumors, demonstrates effectiveness and safety of therapy inBRCAmBCas well. The results of OlympiAD and LUCY trials are represented in the article. Subgroup analysis may define the patient population that would benefit from PARP inhibitors therapy.

Elderly cancer patients represent a very heterogeneous population not only in chronological age, but also in functional status, concomitant diseases and therapy, geriatric syndromes, and, as a consequence, in the tolerability of cancer treatment. The choice of treatment for metastatic breast cancer (mBC) in this category of patients is often a difficult task for oncologists. The emergence of a new class of drugs, inhibitors of cyclin-dependent kinases 4/6 (CDK4/6), has changed the paradigm of treatment of patients with luminal HER2 negative mBC (ER + HER2mBC); however, data on the efficacy and tolerability of these drugs in elderly patients are limited. Pooled subgroup analyzes of studies with CDK4/6 have shown that elderly patients with ER + HER2breast cancer have a clear PFS benefit from the addition of targeted drugs to hormonal therapy. Adverse events are observed more often in combination therapy with increasing age, which requires dose modification and appropriate therapy. In this regard, the drug abemaciclib is very attractive, which is characterized by a lower frequency of neutropenia compared to other CDK4/6 inhibitors, but a higher incidence of diarrhea, which can be controlled by taking appropriate drugs and is not a reason for treatment discontinuation. Careful selection of patients is necessary when deciding on the appointment of any therapy to geriatric cancer patients. Only a comprehensive multidisciplinary approach will make it possible to maximally individualize the approach to the treatment of this difficult category of patients and minimize the likelihood that they will receive excessive or insufficient oncological treatment.

Introduction. Breast cancer is the leader in cancer incidence in theRussian Federation. The tumor is considered extremely heterogeneous and the luminal subtypes of breast tumors occupy a special place, since they are considered relatively favorable in therapy and control of the disease.

Drug therapy for hormone-positive cancer has undergone significant evolution and new anticancer agents have appeared in the arsenal of the oncologist and have shown promising results compared to classical therapy. The search for predictive markers of the effectiveness of new therapy has become of great importance. This marker turned out to be a mutation in the PIK3CA gene – one of the most frequent genetic disorders in breast cancer cells. According to the literature, the presence of this mutation negatively effects on endocrine therapy for breast tumors.

The aim of this study was to analyze the frequency of mutations in the PIK3CA gene among patients with hormone-positive tumors, and the effectiveness of therapy with CDK4/6 inhibitors in this group of patients.

Materials and methods. The material for the study of the mutation in the PIK3CA gene was tumor biopsies of 31 patients and clinical data on the response to therapy with CDK4/6 inhibitors and classical hormone therapy.

Results and discussion. The results of the work showed a high incidence of the PIK3CA mutation among hormone-positive tumors (45%). The mutation resulted in a decrease in both the median time to progression after radical surgery (from 48.4 ± 7.8 months to 30.1 ± 6.0 months) in patients receiving adjuvant hormone therapy and progression-free survival in patients receiving therapy with CDK4 /6 inhibitors (4.2 months versus 9 months). This confirmed the theory that the PIK3CA mutation negatively affects the outcome of hormone therapy.

Conclusions. PIK3CA is an important predictive marker in endocrine therapy for hormone-positive tumors. Its presence not only determines the relatively worse results of treatment, but can also serve as an indication for the appointment of a special series of drugs – inhibitors of this mutation.

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.

Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.

Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.

Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study.

Melanoma of the skin is one of the most aggressive malignant neoplasms. Metastatic skin melanoma has an extremely poor clinical prognosis with a high mortality rate, accounting for 80% of all deaths from skin malignancies. The approaches to the treatment of metastatic skin melanoma have been dynamically developing over the past decade. New drugs and their combinations are becoming more affordable. In connection with the advances in molecular genetics and the development of new targeted drugs, treatment outcomes have significantly improved: first of all, overall survival and the time to progression of the disease, which has set new challenges for continuing research in this area. The development of new treatment options for patients with inoperable and/or metastatic melanoma with a mutation in the BRAFV600 gene is still in high demand. Emerging data from clinical and preclinical studies suggest that synergies can be observed between inhibitors of immune checkpoints and inhibitors of BRAF and MEK. Despite the fact that inhibitors of the BRAF signaling pathway have a high frequency of objective responses, in most cases their duration is short. Inhibitors of immune checkpoints provide a longer lasting effect, but the response rate is relatively low. Combining the two types of therapy can improve survival rates over the long term. This review demonstrates the results of phase III randomized trials that have allowed to determine the current standards in the treatment of metastatic skin melanoma. We also demonstrated our own experience of using a triple combination of targeted therapy with BRAF/MEK inhibitors in combination with PD-1 inhibitors.

Ovarian cancer is one of the leading causes of death from gynecologic cancers in Russia: in 2018, 7616 women died from this disease and the proportion of patients who is under observation for 5 years or more was only 3.4%, which probably indicates very low 5-year survival. At the same time, there was is a tremendous paradigm shift in the treatment of BRCA-associated ovarian cancer. A number of large phase III trials have been published on the use of PARP inhibitors in this subtype of the disease. Their results demonstrated a marked reduction in the risk of disease progression or death with PARP inhibitors after first-line therapy for advanced ovarian cancer. Here we present a comparative analysis of the efficacy of various PARP inhibitors in BRCA-associated ovarian cancer. The relative risk reduction in disease progression or death for olaparib, niraparib and veliparib was 70%, 60% and 56%, respectively and advantage of using these drugs noted in all patient subgroups. Comparative analysis of the safety of various PARP inhibitors was carried out as well, the risks of developing various toxicity were assessed. Based on a comparison of published data on their safety profile, it was concluded that olaparib is the safest drug of this class, especially in the context of therapy on an outpatient basis. Possible ways to optimize the use of PARP inhibitors in disseminated ovarian cancer have been analyzed.

Bone metastases often develop in patients with prostate cancer (PC) as a natural stage in the course of the disease. The skeletal system is the most typical and sometimes even the only site of metastatic prostate cancer. The involvement of bones is a cause of reduced life expectancy and a strong prognostic factor for adverse events, such as bone complications (including the pain requiring surgery or palliative radiation therapy, pathologic fractures and spinal cord compression), resulting in a significant decrease in the quality of life.

The model of therapeutic decision-making in metastatic castration-resistant PC (mCRPC) is still an unsolved problem. Several therapeutic options have been developed recently, that has significantly improved the survival of patients with mCRPC. The presence of multiple active agents provides oncologists with an unprecedented opportunity to tailor their choices to the clinical characteristics of each patient and to each line of treatment, but at the same time it creates the challenge of determining the optimal therapeutic sequence for the individual patient.

In Russia, radium-223 is approved for patients having bone metastases and no visceral metastases. It can be assigned to patients with lymph node metastases and patients with bulky bone metastases if other drugs are contraindicated to them. However, the use of radium-223 is most preferable if a patient has bone metastases and good bone marrow reserve.

Due to the evolution of treatment strategies, the complexity of the process of assessing the dynamics of treatment and the variability of the clinical aspects of the disease, a multidisciplinary approach becomes of great importance today.

The prevalence of prostate cancer continues to increase worldwide. The effectiveness of androgen deprivation therapy for advanced prostate cancer has a time limit, after which castration resistance and disease progression are formed. A part of patients with castrate-resistant prostate cancer has no metastases (according to standard imaging methods). The main goal of treatment of these patients is to prolong the time before metastasis formation. This article presents a review of the current understanding of the molecular mechanisms underlying the inhibition of androgen-receptor signaling with enzalutamide, a second-generation androgen receptor antagonist, and the results of clinical studies of its efficacy and safety in castrate-resistant prostate cancer without metastases. It was determined that enzalutamide stimulates the expression of a new class of genes that are not regulated by dihydrotestosterone. It was found that, in addition to inhibiting androgen receptors, enzalutamide can act as a partial transcriptional agonist. Enzalutamide therapy has been shown to reduce the risk of tumor progression and death in patients with non-metastatic castrate-resistant prostate cancer and is well tolerated. Treatment with this drug increases the time before metastases appear, before the first use of subsequent anti-tumor therapy is necessary, and the period before prostate-specific antigen levels have progressed. Study of mechanisms induced by enzalutamide – inhibition of prostate cancer cells growth and activation of genes contributing to cancer development by enzalutamide-related androgen receptor – can help to clarify possible ways of resistance formation to this drug and possibilities of its overcoming with combined therapy.

The arsenal of available treatments and treatments for metastatic hormone-sensitive prostate cancer (mHRPC) has increased significantly over the past 5 years. Although androgen-preferential therapy (ADT) remains the mainstay of treatment, the addition of docetaxel, abiraterone, enzalutamide, apalutamide, or local external beam radiation therapy improves the outcome of patients with mHRPC and becomes the standard of care. Choosing a therapy to improve treatment outcomes for patients with mHRPC is becoming increasingly challenging as there are different options for this stage of the disease. This article provides an overview of clinical trials that included ADT in combination with chemotherapy, new hormonal therapy, and radiation therapy. We will also consider recent advances in the choice of treatment for men diagnosed with mHPCR and the impact of previous therapy on the subsequent biology of the disease. Options include chemohormone therapy, androgen receptor (AR) targeted therapy in addition to ADT or, less commonly, ADT alone. The choice of treatment should be based on a consideration of the clinical characteristics and characteristics of the disease, as well as taking into account the patient’s preferences, territorial constraints and financial resources.

This review is dedicated to the impact of modern achievements on the definition and diagnostics of castration-resistant prostate cancer (PCa) (CRPC), prognostic factors for its progression, and treatment strategies.

It was proven with new sensitive methods of diagnostics that surgical castration (CS) decreases serum testosterone (T) levels to < 20 ng/dL, while achieving T < 20 ng/dL improves outcomes and delays the development of CRPC. Regular assessment of the T level makes it possible to understand whether this androgen is adequately suppressed in the setting of potential progression of CRPC, given that late dosing may lead to an increase in T level. Improved imaging techniques and biomarker analysis enable early detection of disease progression. Prognostically significant risk factors for CRPC progression include Gleason score, the extent of metastatic spread, hereditary characteristics such as gene mutations affecting androgen receptor (AR) amplification or DNA repair deficiency mutations, prostate-specific antigen (PSA) kinetics, and biomarker levels. Today, treatment options for CRPC have gone beyond androgen deprivation therapy (ADT) to include therapy that blocks T-synthesis and/or suppresses its activity through various mechanisms. Future directions include therapies using new biological targets, drug combinations and personalized therapies. It is necessary to assess the possible reasons for the difference in the pharmacodynamics and pharmacokinetics of androgendeprivation drugs, to study the features of the processes of destruction of drugs under the action of endogenous enzymes and resorption in the subcutaneous or muscle depot, which may cause the resistance to therapy.

The aim of improved treatment and diagnostic options for PCa is to delay its progression to CRPC and to prolong patient survival. Rethinking of the castration concept and advances in understanding the biology of disease progression make it necessary to revise diagnostic and treatment strategies. ADT is a fundamental vector of treatment, and it should be continued even if some new ways of treatment for CRPC are introduced.

This review presents current data on the role of nutritional support in patients with cancer. The main reasons for the decrease in body weight, protein-energy deficiency in the development of malignant neoplasms are described. The data substantiating the appointment of dietary food products in various phases of the disease to patients receiving systemic anticancer therapy (chemotherapy, targeted therapy, immunotherapy) for a long time, and to cancer patients who underwent volumetric abdominal surgery are presented. The mechanisms of intoxication arising as a result of the disease itself, as well as a result of prolonged polychemoor irradiation therapy, are described in detail. The concept and mechanisms of endogenous intoxication syndrome are given. Special attention is paid to the role of the cytochrome system of the liver in detoxification processes. It has been shown that the accumulation of toxic metabolites in cancer disrupts the activity of the organs of detoxification and excretion, metabolites accumulate in tissues, which leads to difficulty in regulating the functions of the body and its protection from intoxication factors. The results of clinical studies of the data are presented and their effectiveness of the use of specialized dietary products of domestic production for cancer patients is presented. Detoxification protein cocktail for cancer patients (based on animal protein), Lactose-free detoxification protein cocktail for cancer patients (based on plant protein) and Drink detoxification for cancer patients (fruit-based). These specialized products have promote tonic, antioxidant, anti-inflammatory, analgesic, anti-toxic, detoxifying properties. It has been shown that dietary products contribute to the restoration of the concentration in the blood of the most important enzymes of antitoxic liver defense – ALT and AST, gamma-HT, total and direct bilirubin, and urea.

Narcotic drugs have become more available for use, but it is obvious that monotherapy of pain syndrome with narcotic drugs is not always effective. Patients sometimes change prescribed opiates to NSAIDs on their own, because it is more effective despite the high risk of complications. In this case patient has a grade 2 pain syndrome associated with bone metastases despite taking the maximum daily dose of tramadol complicated by nausea. Treatment was successfully changed with medium doses of tramadol and dexketoprophen. We consider the combination of narcotic drugs and NSAIDs as opiate-sparing and suggest that dexketoprophen is effective for treatment of pain associated with bone metastases because of the effect on neuropathiс and central components of pain syndrome. We have analyzed the main mechanisms and options for systemic pharmacotherapy of pain syndrome in bone metastases. Some NSAIDs are known to have central analgesic effects. For example, the analgesic effect of ketorolac after an injury of sciatic nerve is explained by its ability to inhibit the synthesis of algogenic peptides in the posterior horns of the spinal cord and the decrease in astrocyte activation. However, it is the dexketoprofen/tramadol combination that is recognized as the most effective in the world.

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).

Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.

Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I² = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I² = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I² = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.

Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1^st line for pts with mBRAF mCRC.

Fibrolamellar hepatocellular carcinoma (FLC) is a relatively rare primary liver tumor of unknown etiology (chronic infections with hepatitis B or C viruses, chronic alcohol poisoning, cirrhosis of the liver), which occurs mainly in the young population. FLK is more often diagnosed already at common stages due to the absence of pronounced clinical manifestations in patients for a long time. In pathomorphological diagnostics, FLC is a cluster of large polygonal eosinophilic cells with a clearly defined vesicular nucleus, surrounded by abundant growths of lamellar fibrosis. In most cases, collagen fibers are arranged in parallel strands; in metastatic tumors, collagen fibers can be arranged haphazardly (the so-called “tangled fibers”).For many years, attempts have been made to identify reliable markers for the detection and differential diagnosis of FLC and to determine the cause of tumors in young patients, and the molecular mechanisms of FLC carcinogenesis have been studied. In 2014 during the full transcriptome analysis of FLC samples, the chimeric transcript DNAJB1PRKACA was discovered, which is formed as a result of deletion of a section of chromosome 19 with a size of 400 thousand nucleotide pairs and leads to the fusion of two genes, which Is found in most FLC samples. Surgery is the only curative treatment of this tumor type and radical method of treating the disease. Given that lymph node involvement is an important prognostic factor, complete periportal lymphadenectomy should be performed as part of radical surgery for patients with FLK. The role and possibilities of locoregional and drug-based treatment methods are not fully clear, and the search for effective treatment regimens and potential targets specific to this form of HCR is urgent. Studies show conflicting results for different chemotherapy regimens and the use of targeted therapy. The literature describes isolated clinical cases of successful use of immunotherapy in patients with PD-L1-expressing tumors. The most important condition for successful treatment is an in-depth study of the molecular mechanisms of FLC carcinogenesis. This review presents current data on epidemiology, classification, clinico-morphological, molecular and genetic aspects, as well as some diagnostic features and FLC treatment modalities.

Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.

Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.

Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).

Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.

Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.

In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of <3 vs ≥3 lines of therapy for metastatic disease in the anamnesis was 9 months vs 4 months, respectively (HR = 4,216; 95% CI [1,334–13,327]; p = 0.0056). In the presence or absence of platinum-containing agents in previous lines of therapy 5 months vs 9.5 months, respectively (HR =1.484; 95% CI [0.48–4.582]; p = 0.4750).

During the treatment with talazoparib adverse events of the 3rd-4th grades were observed in 5 patients (20,8%). These include moderate and severe anemia in 3 patients (12.5%), thrombocytopenia in 1 patient (4%), and neutropenia in 1 patient (4%). The majority of patients (79,5%), which received talazoparib, did not require dose adjustment. The need to reduce the dose to 0.75 mg was noted in 3 patients (12.5%), to 0.5 mg – in 2 patients (8%). Hemotransfusion was performed in 3 patients. For effective therapy safety management regular monitoring of blood parameters is necessary.

Conclusion. Thus, targeted therapy with talazoparib is an effective treatment option for HER2-gBRCA+ mBC.

Introduction. Nowadays the stereotactic radiotherapy (SRT) of patients with clinical stage I-II lung cancer is the choice of the treatment modality for functionally inoperable patients. It shows safety and high efficiency in reaching the local control. Though there is a range of unsolved issues connected with the prediction of treatment efficiency and frequency of complications, an integration of new technologies in the planning and treatment process allows to widen the search of the predictive factors.

Materials and methods. Since 2014, 42 patients (T1N0M0 – 16 patients, T2N0M0 – 26 patients) with clinical stage I-IIa lung cancer have underwent SRT. The majority of patients (38) have been recognized as functionally inoperable due to the concurrent broncho-pulmonary pathology, 4 conditionally operable patients have refused an operation. 11 patients had the primary multiple tumors in their anamneses, 3 patients had a сentral tumor. Used dose fractionation options were: 10 Gy х 5 fractions (n = 29) and 7 Gy х 8 fractions (n = 13) – BED = 100 Gy.

Resuts. The median follow-up was 32 months (range 6–56 months). The 3-year local control was 94%. The isolated local recurrences were not registered. Overall 3-year survival rate was 74% (95% CI, 60–90) and a 3-year tumor-specific survival rate – 84% (95% CI, 71–98). During one-factor analysis a reliable influence on the prognosis of the fractionation regimen (р = 0,04) and, close to reliability, the initial SUVmax level influence (р = 0,07) were revealed. Grade 3 pulmonary toxicity was observed in 4 (9%) patients, one patient with a Central tumor died from pulmonary hemorrhage (grade 5 toxicity). Grade 3 chest pain was observed in 3 (7%) patients, two of them had a rib fracture.

Conclusions. With modern approaches to SRT treatment planning and delivery there should be a search for additional treatment efficiency and toxicity predictors. The total dose delivery regimen and initial tumor SUVmax can be predictive efficiency factors, while the pulmonary tissue volume can be a predictive toxicity factor.

Introduction. Dermatologic adverse events (DAEs) occur in 50-90% of cases during anti-EGFR monoclonal antibody treatment. Positive correlation between the severity of acneiform rash (AR) and the effectiveness of anti-EGFR management is established. Low effectiveness of traditional treatment for AR impairs patients’ compliance, leads to dose reduction or drug discontinuation, affecting treatment results.

Objective. To assess the effectiveness of traditional and proposed combined treatment for AR associated with anti-EGFR monoclonal antibody therapy.

Materials and methods. 44 patients with grade I-II acneiform rash were included in a 12-week study. Patients were divided into 3 equal groups and received different treatment: group 1a – traditional therapy, group 1b – combined continuous therapy, and group 1c – combined intermittent therapy. Assessment of clinical outcomes was performed with DLQI, IGA score, and the NCI CTCAE v. 4.03.

Results. The severity of AR in groups 1b and 1c improved by the end of week 1, and this trend was kept until the end of the study. The improvement was more prominent in group 1c comparing to group 1b. The severity of AR in group 1a improved by the end of week 1. During weeks 2 and 3 there was no significant change. At week 4 a deterioration of the evaluated parameters was registered, and the treatment regimen in group 1a was changed according to the treatment protocols of group 1c with rapid improvement of AR.

Conclusion. Combined intermittent therapy with systemic doxycycline and topical therapy with metronidazole 1% gel and cream with hydrocortisone acetate 1% and fusidic acid 2% showed the best effectiveness and tolerability in patients with anti-EGFR monoclonal antibody-related AR.

Introduction. Breast cancer is a serious medical and social challenge and the statistics around the world look daunting.

Relevance. The incidence of breast cancer is increasing in most countries and this may be due to a number of reasons. First of all, it should be noted the improvement of diagnostic methods, in particular, mass mammographic screening, which allows detecting neoplasms at early stages, before the onset of clinical symptoms. As for mortality rates, in recent years, world statistics show a downward trend in rates.

Goal. To analyze the incidence and mortality rates of breast cancer (BC) in the Moscow Region (MO) for the period from 2011 to 2018. The study of indicators in one of the regions of Russia – MO – is of great importance for determining and predicting the true needs of the population in specialized medical care.

The purpose of the study was to analyze the incidence of breast cancer (breast cancer) in the Moscow Region (MO) for a period of time from 2011 to 2018.

Materials and methods. Some data of the territorial cancer registry of the Ministry of Defense of the Russian Federation on the diagnosis and treatment of patients with breast cancer were used, which will make it possible to determine the needs of this cohort of patients in specialized care.

Results. From 2011 to 2018, 26755 new cases of breast cancer were diagnosed in the Moscow Region. The analysis of the comparative stratification in breast cancer in the medical district made it possible to obtain statistically significant differences indicating an increase in the incidence in the period from 2015–2018 in comparison with the period of 2011–2014. The presented data also indicate a trend towards a decrease in the one-year mortality rate over 8 years: from 6.33% in 2011 to 5.32% in 2018. For the period from 2011 to 2018 (8 years) there is an increase in the number of patients with breast cancer who have been in the medical center under dispensary supervision for 5 years or more.

Conclusions. Analysis of the data obtained on the indicators of morbidity and mortality from malignant neoplasms is of great importance for determining the needs of the population in specialized medical care.

Patients with brain metastases of HER2-positive breast cancer (BC) is a special group of patients who are difficult to treat and have a short life expectancy. The possibilities of whole brain radiotherapy, stereotactic radiosurgery and surgery in such patients are rather limited. Trastuzumab emtansine (T-DM1) showed potential activity in this subset of patients. T-DM1 is an antibody-chemical conjugate (ADC) that delivers directly to HER2-positive cancer cells, thereby limiting damage to healthy tissue. At this point, the efficacy of trastuzumab emtansine has been demonstrated in several randomized trials as a second and subsequent lines of therapy for advanced breast cancer with a favorable toxicity profile of the drug. This article describes a clinical case of a patient with luminal B HER-2 positive breast cancer who, underwent stereotactic radiosurgery and was treated with trastuzumab emtansine as a the second line of treatment for disease progression with metastatic brain lesions after trastuzumab/pertuzumab-containing therapy. Partial regression of metastases with long-term duration of the effect was achieved treatment with trastuzumab emtazine has been being continued for 24 months. Tolerability of therapy was good: thrombocytopenia 2 degree was the main among side effects. The effect has been persisted for 2 years and the patient continues the treatment. Discussion of the results of real clinical practice with well-known studies was carried out.

Lung cancer holds a leading position in the cancer mortality pattern worldwide. The emergence of knowledge about driver mutations heralded a new era in the targeted therapy for lung carcinomas. ALK translocation is identified in 5–7% of non-small cell lung cancer cases. ALK-positive lung adenocarcinomas are associated with specific clinical features, including no or light smoking history and younger age. Alectinib is a novel ALK inhibitor that has been granted a breakthrough therapy status by the FDA to accelerate approval as a second-line therapy after progression during crizotinib therapy.

Here, the case of a patient with metastatic ALK-positive lung adenocarcinoma treated with alectinib has been discussed. Molecular genetic testing for driver mutations makes it possible to personalize approaches to anticancer drug therapy. At the same time, the custom-compounded targeted therapy is more often accompanied by significant objective responses and moderate symptoms of toxicity, which is relevant for patients in critical condition. The experience in using alectinib demonstrates the possibility of its long-term administration with high efficiency and a controlled safety profile.

The abscopal effect was described more than 50 years ago and is a phenomenon in which radiation therapy promotes the regression of metastatic foci remote from the site of radiation. For decades, this effect has been described as a rare, unexplained phenomenon in patients receiving radiation therapy. Today, the abscopal effect is still an exceptional phenomenon: the mechanism underlying it is still not fully understood. It is believed that the abscopal effect is most likely associated with systemic immune responses that occur under the influence of radiation therapy.

We present the case of a 63-year-old patient with advanced peripheral cancer of the upper lobe of the left lung, disease progression in the form of metastatic brain lesions and regression of tumor foci in the lungs after radiation therapy to the brain, while the patient did not receive additional treatment in the form of immunotherapy.

The article examines the history of the abscopal effect, an attempt is made to understand the mechanisms of its occurrence, which can help to further improve the results of treatment of patients with NSCLC using radiation therapy and modern approaches to complex cancer treatment.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that has been approved for the treatment of metastatic non-small cell lung cancer (NSCLC) positive for the secondary T790M mutation of EGFR. Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Almost 25% of patients present with accompanying central nervous system (CNS) metastases at the first diagnosis. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood‐brain barrier (BBB), creating a major unmet need for the development of agents with good BBB‐penetrating biopharmaceutical properties. Although the CNS penetration of first‐ and second‐generation EGFR tyrosine kinase inhibitors (TKIs) is generally low, EGFR‐TKI treatment has been shown to delay time to CNS progression in patients with both in preventing or delaying the onset of CNS metastases, and in leading to intracranial response of preexisting CNS lesions. This is one of the arguments in favor of starting osimertinib upfront rather than initiating treatment with firstor second-generation EGFR-TKIs.

Ramucirumab is a human anti-vascular endothelial growth factor receptor 2(VEGFR-2)monoclonal antibodythat acts on vascular endothelial cells to inhibit angiogenesis. Ramucirumab in monotherapy or in combination with paclitaxel or FOLFIRI has proven to prolong overall survival in patients with pretreated metastatic gastric/gastrooesophageal junction adenocarcinoma. In clinical practice combination with ramucirumab showed promising efficacy with median overall survival in 9,6 months and manageable toxicities. Most common specific adverse events in ramucirumab were impaired wound healing, hypertension, bleeding and perforation. In several article describe dysphonia induced by anti-angiogenic compounds.

Herein, we report on a case a high activity ramucirumab in combination with FOLFIRI. This report aims to present a long-term survivor of recurrent gastric cancer and describe dysphonia induced by ramucirumab.

For more than 10 years, there have been no significant improvements in treatment outcomes for patients with inoperable locally advanced non-small cell lung cancer. At the moment, the standard of treatment for this category of patients is concurrent chemoradiation therapy. At the same time, the 5-year overall survival rate varies in the range of 15–25%. This indicator contributes to the modernization of existing approaches, as well as the search for new ways in the treatment of patients with inoperable stage III non-small cell lung cancer.

One of the promising areas is the combination of chemoradiation therapy with immunotherapy. Thus, the use of Imfinzi (durvalumab, AstraZeneca) as a consolidation therapy in the Phase III clinical trial PACIFIC demonstrated a reduction in the risk of death by about one third in comparison with the standard approach.

We present a clinical case study of a patient with locally advanced non-small cell lung cancer who received treatment in the framework of concurrent chemoradiation therapy followed by immunotherapy with durvalumab, continuing until now. The result of the therapy is the complete response to the specific treatment, recorded according to PET-CT.

Thus, the use of immunotherapy as consolidation therapy represents a promising strategy for improving outcomes after concurrent chemoradiation therapy in patients with inoperable stage III non-small cell lung cancer