Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, namely palbociclib, ribociclib and abemaciclib, have become a new standard of treatment of patients with hormone receptor-positive, HER2-negative disseminated or metastatic breast cancer (HR+ HER2- MBC), regardless of the line of therapy, menopause status and other individual characteristics. Short-term CDK4/6 inhibition leads to reversible arrest in the G1 phase of the cell cycle with restoration of Rb-1 phosphorylation and the complete cell cycle after termination of inhibition. The drugs have individual characteristics despite the similar mechanism of action described in the article. Abemaciclib, which differs from palbociclib and ribociclib in chemical structure, shows higher selectivity for CDK4, less myelosuppressive effect, which makes it possible to take it continuously, greater lipophilicity, and interacts more actively with ATP, resulting in its ability to interact with other kinases as well. Abemaciclib, the only one of all CDK4/6 inhibitors, has been proven effective in the treatment of refractory HR+ HER2-MBC: the proportion of patients with objective effect (OE) was 19.7%, that with disease control was 42.4%, median progression-free survival (PFS) was 5.95 months, median overall survival (OS) was 22.32 months. Abemaciclib combined with fulvestrant in the second-line therapy increases the effectiveness of treatment compared with endocrinotherapy (ET) alone: median PFS increased to 16.9 months from 9.3 (p < 0.001), OE to 35 from 16% (p < 0.001) in the ITT population, median OS to 46.7 from 37.3 months (p = 0.01) for abemaciclib in combination with fulvestrant. The use of abemaciclib in combination with nonsteroidal aromatase inhibitors (NSAIs) compared with aromatase inhibitors (AI) alone in the first-line therapy demonstrated increased median PFS from 14.76 to 28.18 months (p = 0.000002) and increased OE (from 37 to 49.7% (p = 0.005) in the ITT population. Diarrhea is the common adverse event of abemaciclib, which develops in 82–90% of patients. It does not exceed severity level 3, the frequency of the latter does not exceed 13%, diarrhea is reversible, and can be stopped by using antidiarrheal drugs. ET in combination with abemaciclib makes it possible to improve the effectiveness of treatment in the most prognostically unfavourable patient population.

Luminal metastatic HER2-negative breast cancer remains one of the most common cancers in oncological practice. This disease still remains incurable. Endocrine therapy remained the standard therapy of choice for disseminated patients for a long time. The search for new effective drugs, development of strategies that can overcome primary and secondary resistance to endocrinotherapy has shown that the CDK4/6-inhibitors group can improve not only the short-term treatment outcomes, but also affect the overall survival of patients, which has been demonstrated in a number of phase III studies. Along with that, the use of CDK4/6 inhibitors maintains a good quality of life, allows patients to maintain professional and social activities, which is of great importance for long-term prospects. Given that the endocrine therapy combined with CDK4/6-inhibitors today is the new standard of therapy in patients with luminal HER2- negative breast cancer, knowing how to use this therapy in daily clinical practice is crucial. Know and apply innovative drugs in clinical practice and the management of regimen toxicity always my work demands close application. This article provides an overview of the data on the efficacy of ribociclib based on phase III registration studies. It also presents its own clinical experience demonstrating the feasibility of using a new group of drugs in patients both in pre- and postmenopausal women. The authors discussed the issues related to the modification of the regimen due to the toxicity of therapy, in particular, neutropenia and hepatotoxicity. They also showed the possibility of managing adverse events with the preservation of a long-term effect with no loss in quality of life.

Germline BRCA1/2 mutations account for about 10% of all breast cancer. BRCA1/2 proteins are involved in homologous recombination - DNA double-strand break repair mechanism. Poly-(ADP ribose) polymerases (PARP) are required to repair DNA single-strand breaks through base excision repair. PARP inhibitors represent a modern option of treatment of metastatic HER2 negative breast cancer with germline BRCA1/2 mutations. Mechanism of action of PARP inhibitors is based on the concept of synthetic lethality under conditions of BRCA dysfunction, when both DNA repair mechanisms, homologous recombination and base excision repair, are impaired. This leads to the apoptosis of cancer cells. Currently two PARP inhibitors are registered in Russia for the treatment of BRCA-associated metastatic HER2 negative breast cancer – olaparib and talazoparib. Efficacy of PARP inhibitors olaparib and talazoparib versus standard chemotherapy has been studied in very similarly designed phase III trials OlympiAD и EMBRACA. Benefit in the progression free survival, acceptable toxicity profile and positive impact on quality of life support inclusion of PARP inhibitors in treatment schemes of metastatic BRCAassociated breast cancer. Very important is the role of PARP inhibitors in treatment of very aggressive triple negative breast cancer with limited number of effective therapy options. We represent here a clinical case of treatment of metastatic triple negative breast cancer with talazoparib in 4^th line of therapy.

The review presents the results of studies of fulvestrant in metastatic breast cancer (MBC). Hormone therapy is an effective method of treating hormone-positive metastatic breast cancer even in the presence of visceral metastases in the absence of a visceral crisis and without detected resistance to endocrine therapy. During the COVID-19 pandemic, hormone therapy is safer for patients with hormone-positive MBC than chemotherapy, since it does not lead to immunosuppression. Fulvestrant is a “pure antiestrogen”, it has a greater affinity for estrogen receptors than tamoxifen. Fulvestrant is both a competitive antagonist and a selective estrogen receptor degrader (SERD), this mechanism of action provides complete blocking of the estrogen signaling pathway. In the phase III CONFIRM study, the optimal dose of fulvestrate was determined to be 500 mg once every 28 days, with a loading dose of 500 mg on day 15 of the first month of therapy. In the FALCON phase III study (n = 462), which included postmenopausal MBC patients who had not previously received any endocrine therapy, fulvestrant 500 mg was compared with the aromatase inhibitor anastrozole. Significant improvement in PFS was achieved with fulvestrant therapy compared to anastrozole: 16.6 months in the fulvestrant group versus 13.8 months with anastrozole [OR = 0.797; 95% CI 0.637–0.999; p = 0.0486]. A subgroup analysis showed that patients without visceral metastases can benefit most from taking fulvestrant. In all studies fulvestrant 500 mg has demonstrated a good toxicity profile, so it is being studied as a component of combined endocrine therapy. In the PALOMA-3 study the combination of fulvestrant with palbociclib (CDK4/6 inhibitor) demonstrated a median PFS 9.5 months, compared with monotherapy with fulvestrant – 4.6 months (HR = 0.46, p < 0.0001). In the MONALEESA-3 study, the median PFS in patients receiving ribociclib with fulvestrant was significantly higher compared to those taking placebo with fulvestrant: 20.5 months and 12.8 months, respectively (HR = 0.593; 95% CI: 0.480–0.732; p < 0.001). In the MONARCH-2 study the combination of fulvestrant and abemaciclib was studied in the second line of therapy, the median PFS was 16.4 months in the group of fulvestrant and abemaciclib, and 9.3 months in the group of fulvestrant and placebo (HR = 0.553; 95% CI 0.449-0.681; p < 0.0001).
Fulvestrant has a satisfactory toxicity profile, does not require supporting therapy, and is included in the clinical recommendations for monotherapy and combination therapy.

In practice, all patients with ER (+) primary breast cancer should conduct adjuvant hormone therapy to suppress the growth of tumors stimulated by estrogens. Five-year tamoxifen treatment reduces breast cancer mortality for 30%, and aromatase inhibitors (for postmenopausal women) reduces it by up to 40%. After five years, long-term relapses still occurred, the risk of which can be reduced by the expansion of adjuvant hormone therapy for more than 5 years. At the population level, the treatment can show relatively moderate and sometimes toxic effects; therefore, it is extremely important for modern clinical practice to identify patients with risk of relapse within the first five years small enough for the therapy to be safely canceled for this period, as well as patients with a risk of relapse high enough to justify a longer treatment. Currently, little data is available from clinical trials regarding the second problem. Recent EBCTCG studies have consistently shown a risk of relapse within 5–20 years in all patient groups. However, the risk varies greatly depending on the size of the tumor and the status of the lymph nodes.
The tumor grade (G) and the proliferation index (Ki67), supplementing the information on the TN stage, demonstrate a high degree of correlation between each other. The only patients who have a relatively low frequency of long-term recurrence (which allows them to be assigned to a very low risk group) are patients with a low tumor grade pT1N0. Prognostic molecular signatures have been proven to be clinically useful (in addition to clinical and morphological characteristics) in identifying patients with an extremely low risk of relapse who can safely avoid chemotherapy.
In clinical trials of adjuvant hormone therapy with a long follow-up period (up to 20 years), a delayed (over five years) recurrence of estrogen-receptor-positive (ER+) breast cancer was noted. Based on these observations, a number of researchers offer longer hormone therapy (exceeding the five-year standard).

The choice of first-line therapy for metastatic skin melanoma has become quite a difficult task in the last few years: a practicing oncologist has got drugs of different classes with different mechanisms of action – immune checkpoint blockers and BRAF/MEK tyrosine kinase inhibitors. In this study, the authors have tried to systematize their own experience and current scientific information about the treatment of patients with metastatic skin melanoma in the first and subsequent lines of therapy. The paper discusses the importance of correct initial assessment of the patient’s condition and prevalence of the process, the role of currently available biomarkers in metastatic skin melanoma, as well as the effectiveness and safety of possible first-line therapy options for this disease. Due to the lack of data for direct comparison of combined immunotherapy, combined targeted therapy, triple combination of BRAFi + MEKi + aPDl1 blockers and aPD1 monotherapy obtained from randomized studies, we have to draw parallels between studies with different diagnoses and different patient populations. Since the practicing oncologist has to do the same thing in his or her daily work, we believe that our review will be very useful for these doctors. The article also discusses the possibility of using drug therapy in the second and subsequent lines and a successful strategy to return to previous treatment in some cases. The clinical observation of a patient with metastatic foot skin melanoma, which has been observed in our department since 2010, is given as an illustration of the success of sequential treatment tactics with different drugs. Clinical observation shows the success of returning to some previously used therapy lines, including after the progression on them.

Merkel cell carcinoma is a rare and aggressive skin tumor that is difficult to treat even at early stages. Treatment approaches for advanced disease are limited and standard chemotherapy provides short-lived disease control in half of patients without significant impact on the overall survival. The new immunotherapy with anti-PD-1/PD-L1 inhibitors allows to improve clinical outcomes of this disease. Avelumab is a fully human IgG1 monoclonal anti- PD-L1 antibody that blocks the interaction between programmed cell death ligand 1 (PD-L1) on tumor cells and programmed cell death-1 receptor (PD-1) on T cells, thereby elimination immunosuppression in the tumor microenvironment. Avelumab provides disease control in 43,2% of the patients with metastatic/locally advanced unresectable Merkel cell carcinoma for the second and subsequent lines treatment with the objective response rate (ORR) 33%. The response was ongoing for ≥ 6 months in 86% of patient with median duration of response 40,5 months. Responses occurred irrespectively of PD-L1 expression and presence of polyomavirus in tumor cells (MCPyV), 3-year overall survival rate reached 32%. Avelumab is more effective for the first line of treatment, providing the disease control in 78,6% the patients with ORR 71,5% lasting for ≥ 6 months. Treatment is well tolerated for the first, second and subsequent lines, demonstrating the adequate safety profile. The most common adverse events were fatigue, diarrhea and nausea.
There were 7 patients in Russia treated with avelumab for metastatic/locally advanced unresectable Merkel cell carcinoma.

Introduction. Currently, numerous studies are published by authors of different countries to demonstrate the effectiveness of noninvasive methods in the diagnosis of melanoma.
Methods. A systematic search was conducted independently in the databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) until April 2020 according to certain inclusion criteria. Data extraction was carried out independently, followed by generalization using descriptive tables. Due to the heterogeneity of the included studies and the impossibility of carrying out a meta-analysis in view of this, we performed a narrative description.
Results. A total of 765 potential publications for inclusion were found and checked, of which 53 were included. By design, the studies were assigned to studies of simultaneous design – 40, to randomized clinical trials – 7, to meta-analysis – 6. Data in the included publications on 76802 skin neoplasms were reported, of which 9070 were melanomas. The extracted data were summarized in descriptive tables.
Conclusion. With continuing technological progress, the development of noninvasive imaging technologies in the diagnosis of skin melanoma should follow the path of cost-effective, simple and accurate diagnosis.

Сervical cancer is recognized as one of the leaders in mortality from gynecological oncological diseases. The incidence and mortality from cervical cancer over the past 10 years remained at a consistently high level. For a long time, the only treatment option for metastatic and/or recurrent cervical cancer was cytotoxic chemotherapy, but its results remained extremely unsatisfactory: the 5-year overall survival rate was about 12%. This article is devoted to a review of the current possibilities of targeted and immunotherapy of metastatic and/or recurrent cervical cancer. We reviewed the most recent studies in the field of the effectiveness of antiangiogenic therapy including a critical and detailed analysis of the results of the GOG-240 phase III study. The data of modern literature in the field of immunotherapy using PD-1 / PD-L1 signaling pathway inhibitors in metastatic cervical cancer has been studied. It was found that a significant number of patients (34-95%) showed increased expression of PD-L1 in the tumor tissue, and 3-6% of patients showed a high level of microsatellite instability (MSI) in the tumor, which reveals the possibility of immunotherapy for this disease. We also conducted a review of ongoing clinical studies on the use of targeted and immunotherapy of advanced cervical cancer and the prospects for changing the “landscape” of treatment for this disease were assessed. On the example of a clinical case of treatment of a real patient, the possibilities of modern targeted and immunotherapy of metastatic cancer of the cervix uteri were analyzed, which gave a possibility to ensure long-term survival for the patient with an initially poor prognosis.

In 2011, a standard approach to the treatment of primary ovarian cancer (OC) included a cytoreductive surgery, which could be performed after 2–3 cycles of neoadjuvant chemotherapy, and chemotherapy consisting of platinum and taxanes. Such approach was provided for all patients, regardless of tumour histology and any molecular biological and genetic factors. The most complete picture of management and therapy of patients can be made using the treatment of a specific patient as an example. After application to the N.N. Blokhin National Medical Research Center of Oncology in 2011, the patient with OC received standard primary therapy and subsequent treatment of the recurrent disease, which was accompanied by various types of adverse events resulting in the poor quality of life for the patient. The data that some patients with OC have a BRCA1/2 mutation that is significant for prognosis and treatment came to hand later and, unfortunately, the awareness of a significant germinal BRCA1 mutation was of no use to the woman any longer. The life expectancy of this patient was 47 months. This is the average life expectancy for patients with stage IIIC OC.
Major changes have been brought in the primary therapy of OC. If a diagnosis of low-grade IIIC ovarian adenocarcinoma was established in this patient today, needless to say that the BRCA1 mutation would be identified during the first-line chemotherapy, and in case of full or partial treatment effect, we would prescribe olaparib as maintenance therapy to the patient. Considering the fact that the median progression-free survival has not yet been achieved in the patients of SOLO-1 study, who received olaparib therapy, and is only approaching 54 months, it can be assumed that even the first relapse could not have developed in this patient.

The standards of treatment for metastatic renal cell carcinoma (mRCC) have changed significantly from unsuccessful attempts of radiation and cytostatic therapy to the encouraging results of targeted therapy and specific immunotherapy. Sunitinib has got into the practice in 2006, and now it`s one of the most studied and approved. Sunitinib is one of the first oral targeted drugs for RCC. It affects such receptors as VEGFR1, 2, 3; PDGFR, FGFR, c-KIT, and RET, which take part in the pathologic angiogenesis, tumor growth, and metastasizing. Moreover, sunitinib stimulates the growth and development of lymphatic vessels, that deliver immunocytes to the tumor.
The advantage of sunitinib over non-specific immunotherapy has been proven by Motzer et al. The randomized trials COMPARZ, RECORD-3, and SWITCH have confirmed that sunitinib is more effective than several targeted drugs (pazopanib, everolimus, and sorafenib respectively) as the first line of treatment for mRCC. The randomized trial of the 3rd phase CARMENA has demonstrated the importance of sunitinib monotherapy for mRCC of intermediate and poor prognosis. In general, sunitinib has been proven to be an effective first-line drug for mRCC, as it`s evidenced in the comprehensive metaanalysis of real-world data and randomized controlled trials published between 2000 and 2017. Nowadays, despite the success of the immunotherapeutic direction, tyrosine kinase inhibitors, and particularly sunitinib, rightfully remain the standard for mRCC of favourable prognosis, the treatment option for worse prognosis in case of contraindications for other methods of therapy, and it` s also used in subsequent therapy lines.

Pain is an important problem in oncology patients. Depending on its intensity, for pain treatment, analgesics of different pharmacological classes are used. According to WHO recommendations, for nociceptive pain treatment in oncology patients, non-steroidal antiinflammatory drugs (NSAIDs), mild and potent opioids are the essential medications. If in pain formation along with the nociceptive pain component, a neuropathic one is present, antiepilepsy drugs, tricyclic antidepressants, local anesthetics are added. Apart from these medicines, adjuvants are used. These agents potentiate the analgesic endpoint of NSAIDs and opioids, correct their adverse effects. Often, intensive pain development is driven by bone metastases, which form in oncologic processes of different primary localization. Herewith, patients could suffer from constant as well as from paroxysmal, “breakthrough” pain. The efficacy of NSAIDs in oncology patients is due not only to analgesic effect but also to their action on inflammatory processes in areas of tumor formation and growth as well as in metastatic foci. Dexketoprofen trometamol is an effective and safe NSAID, a water-soluble salt of a dexketoprofen dextrorotatory stereoisomer. The preparation has a good lipid and water solubility. Thus, dexketoprofen trometamol can rapidly absorb, create therapeutic concentrations in blood serum, and penetrate through brain-blood barrier. It produces a significant and fast analgesic action in different diseases, which is related both to central analgesic mechanisms and to anti-inflammatory effect in peripheral tissues. Dexketoprofen trometamol efficacy is proven in bone pain related to oncological disease. The availability of intravenous solution and the prompt action at oral administration allow using the medicine for “breakthrough” pain. The medication significantly potentiates the action of mild and potent opioids at combined therapy, which allows to use opioid analgesics in lower doses.

This article presented a review of the literature on the features of nutritional support for oncohematological patients who have undergone allogeneic (alloHSCT)/autologous hematopoietic stem cell transplantation (autoHSCT).
Bone marrow transplantation associated with a high risk of developing nutritional deficiencies. Nutritional support (NP) is indicated for patients undergoing alloHSCT and autoHSCT in order to reduce the incidence of infectious complications and reduce the risk of developing severe forms of acute and chronic GVHD. Currently, there are recommendations for conducting NP in alloHSCT, while there are no recommendations for patients with autoHSCT.
An important task in planning NP is the calculation of the daily energy requirement. Bone marrow transplantation accompanied by a prolonged negative nitrogen balance. The protein requirement for alloHSCT is significantly higher than for patients with chemotherapy alone – 1.5–2 g/kg per day. An effective method of controlling the needs of hematological patients during the analysis of HSCT and alloHSCT is the calculation of the nitrogen balance and the daily protein norm.
In this article was analyzed the role of macronutrients and immunonutrients in the recovery of patients during alloHSCT. It has been shown that low levels of vitamin D and vitamin A increase the risk of development and the severity of the transplant versus host reaction. The addition of omega-3 fatty acids helps maintain an optimal proportion of calorie intake from lipids, as well as maintain the necessary level of triglycerides in the blood. The article presents data on reducing the risk of developing acute GVHD with systemic addition of omega-3 fatty acids.
For a final assessment of the effect of the neutropenic diet on the development of infectious complications in oncohematological patients, randomized prospective multicenter studies with the development of a unified approach in choosing a diet for HSCT are needed.

Background. Ramucirumab is a monoclonal antibody that inhibits the vascular endothelial growth factor receptor-2 (VEGFR2). The study is aimed to analyse prognostic factors for survival in patients with disseminated gastric cancer who received ramucirumab in the second-line therapy in ’real-life’ clinical setting of Russia (RAMSELGA).
Methods. We retrospectively analysed the outcome of 163 patients aged 20–78 years from 11 oncological centres in Russia. Survival analysis was performed using the Kaplan – Meier model, and regression analysis was performed using the Cox model.
Results. In a univariate analysis of overall survival, 5 factors were identified as independent factors of an unfavourable prognosis: 1) age <65 years (RR 0.542; 95% CI 0.302–0.971; p = 0.039); 2) time to tumour progression on the first-line therapy is not more than four months. (RR 0.161; 95% CI 0.105–0.246; p = 0.0000); 3) a low grade tumour or colloid cancer (RR 1,868; 95% CI 1,063–3,284; p = 0,030); 4) peritoneal metastasis (RR 1.549; 95% CI 1.026–2.339; p = 0.037); 5) ascites or pleurisy (RR 0.624; 95% CI 0.424–0.920; p = 0.017). In a multivariate analysis, favourable prognostic factors of overall survival of patients included age – 65 years or older (OS 2.288; 95% CI 1.240–4.220; p = 0.008) and time to tumour progression on the first-line therapy – more than 4 months (OS 6.650; 95% CI 4.221–10.477; p = 0.000).
Conclusion. Despite an active search, prognostic factors for survival in patients that are universal for dGC have not yet been found. To build a universal prognostic model, a very thoughtful analysis considering not only clinical and laboratory, but also pathomorphological and molecular genetic characteristics is required.

Introduction. Sufficient experience has been gained with the use of target drugs in patients with ALK-positive non-small cell lung cancer (NSCLC) over the past years. The multikinase inhibitor crizotinib was the first drug approved for use. The drug passed the accelerated registration in the United States, showing an indisputable advantage over standard chemotherapy both in untreated patients and patients, who had previously received cytostatic therapy. Brain metastasis is the manifestation of acquired resistance to crizotinib in almost half of patients, which requires local monitoring and/or prescription of the nextgeneration ALK inhibitors – ceritinib or alectinib. Experience has proven that it is sequential targeted therapy with the nextgeneration ALK inhibitors with a wider spectrum of anti-tumour activity and penetrating the blood-brain barrier that significantly improves the overall survival of these patients after disease progression on crizotinib. It appears then that the second generation drugs – ceritinib and particularly alectinib – show more impressive results when they are prescribed in the firstline therapy and have now replaced crisotinib in the clinical guidelines. Crizotinib has long remained the only target drug to treat ALK-positive patients in the Russian Federation.
Material and methods. In our work, we analysed the crizotinib therapy outcomes in 104 patients with translocation in the ALK gene. The drug was prescribed in a standard dose of 250 mg orally twice per day. Treatment continued until disease progression or intolerable toxicity.
Results. The objective response was 56.8%. The median time to progression was 13 months; the median overall survival was 46 months.
Conclusion. The obtained data are consistent with previously published data and confirm the effectiveness of the drug in comparison with the previously available universal standard – combination chemotherapy.

Introduction: Squamous cell carcinoma of the oral cavity is one of the most common head and neck cancers with an aggressive course and high mortality rates. The aim of the study was to determine the EGFR expression levels in tumor tissues in patients with squamous cell carcinoma of the tongue and oral mucosa depending on the efficacy of the therapy.
Material and methods: The study included 60 patients with squamous cell carcinoma of the tongue and oral mucosa T3-4N0-1M0. The main group included 30 patients receiving chemotherapy (cisplatin/fluorouracil) in combination with targeted therapy with cetuximab. The control group included 30 patients receiving chemotherapy without cetuximab. Both groups were divided into two subgroups: sensitive and resistant.
Results: In treatment-resistant patients of the main group with cetuximab, the average EGFR expression was twice lower than the initial levels (p = 0.0080) and 1.7 times higher than in treatment-resistant patients of the control group (p = 0.0157). In treatment-sensitive patients, the average EGFR expression was 19.8 times lower (p = 0.0020) than initial values and 14.9 times higher (p = 0.0067) than in treatment-sensitive controls.
Conclusions: A natural decrease in the EGFR expression in tumor tissues due to the targeted therapy was revealed. However,  some patients were resistant to cetuximab, which dictates the need to search for predictors of targeted therapy efficacy in patients with locally advanced squamous cell carcinoma of the tongue and oral mucosa.

Introduction. In modern recommendations for the treatment of localized small cell lung cancer (SCLC), preference is given to socalled «early» chemoradiotherapy (CRT), which has a number of limitations due to its pronounced toxicity. With regard to prophylactic brain irradiation (PBI), although there is reliable evidence that it is necessary, PBI cannot be performed on all patients due to the frequent refusals of the patients themselves and the accompanying neurological pathology. The article presents own experience of therapy of patients with localized SCLC with the analysis of accumulated data.
Materials and methods. Retrospective assessment of treatment results of patients with localized SCLC was carried out. The analysis included data on 63 patients. 47 patients received simultaneous CRT and 16 patients received consecutive CRT. The results of simultaneous CRT were evaluated first. 27 patients received “early” CRT, while 20 patients received “late” CRT.
Results. The PFS median for the group of early CRT was 9.5 months (95% CI 4.2–14.9) and for the group of “late” CRT it was 11.8 months (6.4–17.1). The difference is statistically unreliable. The median of total survival rate was higher in the group of “early” CRT, despite the fact that PFS was lower. The OS median in the group of “early” CRT was 27.9 months (95% CI 2.1–53.7), and in the group of “late” – 24.8 months (95% CI 13.3–36.1). The difference is statistically unreliable. Prophylactic brain irradiation (PBI) in the group of patients with simultaneous CRT was received by 26 patients (55%). The results of overall survival show the crucial importance of PBI in patients with localized SCLC. The OS median in patients who received PBI was 45.9 months (95% CI 21.2–70.5), in patients who did not receive PBI – 21.7 months (95% CI 14.3–29). The difference is statistically significant, p = 0.01. As for complications, 2nd degree esophagitis was recorded more frequently in the group of early CRT – 57% in the group of early CRT and 42% in the group of late CRT, 3rd degree esophagitis was recorded in 1 patient in each group, the difference is not significant. Grade 3–4 hematological toxicity was observed in 5 patients in the group of early CRT and 2 patients in the group of late CRT, the difference is also unreliable. The OS median in the group of patients who received consecutive CRT was 27.1 months (95% CI 18.2–37.6), and the OS median in the group of patients who received simultaneous CRT was 27.9 months (95% CI 18.9–36.9).
Conclusions. The obtained data show an unreliable advantage of the “early” CRT over the “late” CRT in terms of overall survival. However, no differences in median time before progression of both local and general ones were obtained. It is extremely important to perform PBI in patients with localized SCLC, as the survival rate in the assessed group of patients doubled.

The relevance: more than 60% of cases are due to early breast cancer (EBC). Priority is the treatment of patients with early breast cancer, provided that the maximum quality of life (QL) is maintained. During or after complex treatment, more than half of patients with EBC report the occurrence of functional disorders that reduce the QL.
Aim: to evaluate the event-free survival rate (EFS) of EBC patients undergoing rehabilitation within the framework of a biopsychosocial approach in the course of complex antitumor treatment.
Materials and methods: the study involved 228 patients with EBC who received complex treatment from 2015 to 2019. In the prospective part of the study, 114 patients were subjected to rehabilitation measures in the framework of a biopsychosocial approach that considers both biological features of functional restriction and psychosocial disorders, a multidisciplinary team of specialists worked with all patients. In the control group, 114 patients were selected retrospectively and underwent physical and psychological rehabilitation as prescribed by a doctor. Patients of both groups are divided into subgroups depending on the availability of preoperative chemotherapy. Event-free survival was assessed over a 2-year follow-up period. Events were accepted as censored events: relapse, metastases, the occurrence of another cancer, a new concomitant disease, an exacerbation of concomitant pathology, and death.
Results: Rehabilitation measures within the framework of the biopsychosocial model improve the indicators of EFS in patients with EBC. The use of a biopsychosocial approach in rehabilitation increased EFS by 3.8 months. The results of multivariate analysis, reducing the risk of occurrence of the event EBC patients undergoing rehabilitation within the framework of the biopsychosocial approach in the presence of neoadjuvant chemotherapy was 28%, in patients of younger age group (25–44 years) was 29%, in patients in menopause – 25%.

At the moment, there are a huge number of risk factors for the development of a tumor process in the ovaries. One of the fundamental niches that allow us to suspect the presence of an imbalance in the body, and the presence of neoplasms is laboratory diagnostics. The purpose of our work was to evaluate changes in laboratory blood tests as a predictor of the development of oncological tumor process in the ovaries in patients of reproductive age (18-40 years). The collection and processing of laboratory data of 168 outpatient and inpatient medical histories of patients of reproductive age, operated on the basis of the Department of oncogynecology of the sbuz SOKOD for tumors and ovarian tumours from 2012 to 2015. Statistical analysis was performed using the statistical package SPSS21, license number 20130626-3 (An IBM Company; USA) and Microsoft Excel (Microsoft; USA). To achieve this goal, the patients were divided into groups according to the who morphological classification of 2013. A study of clinical blood analysis and biochemical blood analysis at the preoperative and early postoperative stages of treatment was conducted. The CA-125 titer was evaluated in two stages: as a qualitative and quantitative indicator. A study was also conducted for the presence of a genetic mutation in the BRCA 1 and 2 genes by taking a blood sample. In conclusion, we can conclude that on the basis of laboratory data it is impossible to conduct a differential diagnosis between tumors and tumor-like formations of the ovaries. When evaluating changes in General clinical blood tests, no significant changes were detected. Our work in a group of patients of reproductive age revealed the absence of mutations in the BRCA 1 and 2 genes. There was a significant increase in the tumor marker of the CA-125 titer (p = 0.015) in a group of patients with tumors and ovarian tumours aged 18–40 years.

Restrictions on the cancer care in an epidemic are observed in the most countries of the world. The first small publications gave information of the increased susceptibility of cancer patients to a new infection which led to the postpone of elective surgery, initiation of adjuvant therapy, and the transfer of specialist consultations to telemedicine. The cases of infections of medical personnel, as well as the reassignment of clinical units and clinics that previously assisted cancer patients to the treatment of patients with COVID-19, also contributed. This article presents the experience of treating viral infections in cancer patients from different countries. On the example of colon cancer, treatment approaches are considered that, in conditions of increased epidemic danger, will allow our patients to provide effective antitumor treatment. We recommend to use short course of radiotherapy with chemotherapy in patients with locally-advanced rectal tumors; short course of adjuvant chemotherapy in stage 3 colon cancer; rational decisions for choosing regimen in 1st and subsequent lines of systemic therapy in patients with metastatic disease.

On April 27, 2020, COVID-19 pandemic affected more than 2,5 million of people in more than 200 countries and caused 185 000 deaths. Healthcare systems have come under enormous stress. In COVID-19 pandemic oncological patients face two serious challenges: the risk of severe infectious disease course and the risk of malignant tumor progression. Forced correction of existing oncological standards of care is based on expert and professional community opinions, and daily gaining experience. The issue resumes the data on COVID-19 influence on liver function among the patients with chronic liver diseases and hepatocellular carcinoma. The guidance on HCC management in COVID-19 pandemic are provided.
More than 1,5 million of people suffers from the liver pathology caused by chronic virus hepatitis, alcohol consumption, nonalcoholic fatty liver disease. Mild COVID-19 is often followed by transient liver function disorder which do not need specific treatment. Severe COVID-19 lids to the increase of aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), to the decrease of serum albumin in most cases.
Regarding the HCC treatment preference should be given to telemedicine, limitation of contacts in health-care facilities, outpatient treatment, including oral medication (tyrosine kinase inhibitors), and if possible delay of invasive procedures with the help of bridge-therapy and active monitoring. Selecting the patients for surgery, ablation or transarterial chemoembolization (TACE) patients with minimal risk of decompensation, with maximum treatment benefit (on the base of prognostic scales), with lack of comorbid should be preferred. Selective and super selective TACE with drug-eluting beads or radioembolization should be used to reduce the risk of immunosuppression and postembolic syndrome. Live organ transplantation should be considered to be postponed. Targeted therapy could be a temporarily alternative to invasive procedures.

Achieving a pathologic complete response as a result of neoadjuvant treatment is associated with improved prognosis in breast cancer. The CREATE-X trial showed a significant survival improvement with capecitabine treatment of patients with residual invasive disease following neoadjuvant chemotherapy, and the KATHERINE trial demonstrated a significant benefit of trastuzumabemtansine (TDM1) in patients with HER2-positive breast cancer who did not achieve a pathologic complete response, so we have a lot of interesting alternatives of post-neoadjuvant treatments for high-risk patients. The discovery of molecular markers of resistance to endocrinotherapy (cyclin-dependent kinases (CDK 4/6), ER mutation (ESR1), mTOR signaling pathway, co-expression of ER+/HER2+) and inhibitors to them expanded the possibilities of endocrinotherapy not only in advanced and metastatic breast cancer, but also in residual ER+ tumors.
The pCR rates in hormone receptor-positive breast cancer after neoadjuvant chemotherapy are around 10%, which is much lower than the values observed in HER2-positive and triple negative subtypes, so new strategies are needed to improve pCR rates in this subgroup, even though the adjuvant endocrine therapy impacts significantly the outcomes of this patients. The cyclin-dependent kinases (CDKs) are serine–threonine kinases that regulate cell cycle progression from the G1 to the S-phase during mitosis. CDKs activity can be abnormally increased or dysregulated in breast cancer, leading to a constant stimulus for cell proliferation and survival, which is a known mechanism of resistance to endocrine treatment. The CDK inhibitors act on CDKs and block their activity, thereby restoring the cell cycle regulation. In studies with metastatic hormone receptor-positive breast cancer patients, the combination of a CDKis with first or second-line endocrine therapy showed significant improvements in progression-free survival and response rates. Evolving techniques such as next-generation sequencing and gene expression profiles have improved our understanding of the biology of residual disease and also the mechanisms involved in treatment resistance.

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.

Introduction. The study of mutation in BRCA1/2 genes was first initiated in the USA and Europe, and later in Russia. Statistics indicate that women with the BRCA1/BRCA2 mutation have a higher risk of breast and/or ovarian cancer than the general population. According to different authors, the average cumulative risk among BRCA1 carriers is 65% (range 44–78%) for breast cancer and 39% (range 18–54%) for ovarian cancer. For mutation carriers in the BRCA2 gene, the risk for breast cancer is 45–49%, while the risk for RNA is 11–18%. However, in patients already diagnosed with breast cancer or ovarian cancer, the risk of a second tumor persists throughout life and may remain high even in old age. Treatment of BRCA-associated breast cancer and/or ovarian cancer is almost the same as treatment for sporadic cancer, and includes surgical, radiation, and drug anticancer therapy. However, there are some features that need to be considered in clinical practice.
Clinical case. In this article we present the clinical experience of the treatment of a 32-year-old patient with BRCA1-associated primary multiple synchronous breast cancer and metachronous uterine tube cancer. In July 2015, the patient was diagnosed with synchronous cancer of both breast (Luminal A right breast cancer and Luminal B left breast cancer). As part of a treatment and with the patient’s consent, a bilateral adnexectomy was performed. In the histological examination of the operating material, the uterine tube cancer was diagnosed in situ. From 16.03.2016 to the present time the patient receives adjuvant endocrinotherapy without signs of disease progression.
Conclusion. This clinical case study presents the importance of a combined approach to the treatment and prevention of BRCAassociated cancer.

Immunotherapy is the most promising method in the treatment of lung cancer, especially in connection with the rapidly growing development of monoclonal antibodies aimed at inhibiting immune checkpoints: anti-CTLA-4, anti-PD-1, anti-PD-L1. Classic immuno-mediated adverse events that occur with this method of treatment can affect several organs, including the lungs. Pneumonitis is a potentially life-threatening complication and often requires rapid treatment with high doses of corticosteroids and antibacterial drugs.
We present the case of a 67-year-old patient with primary multiple malignant tumors of the larynx and left lung after combined treatment and incomplete treatment with Nivolumab, complicated by immuno-mediated pneumonitis.
This report highlights the importance of treating patients with contraindications to chemotherapy when specific antitumor treatment is required, as well as timely detection of a rare but dangerous adverse event: immuno-mediated pneumonitis that occurs during treatment with immune checkpoint inhibitors.
Thus, knowing the frequency of adverse events when using PD-1 and PD-L1 inhibitors, as well as the possible presence of comorbidities in patients, will make it easier for doctors to make informed decisions in the treatment of patients, and understanding the interaction of the tumor and the immune system will help determine the best predictors of response and further improve the results of treatment of patients with NSCLC.

In accordance with the clinical recommendations of the World Health Organization and the Ministry of Health of the Russian Federation, the main analgesics for the treatment of chronic cancer pain are non-opioid and opioid analgesics, given stepwise in combination with co-analgesics and adjuvant drugs. As a rule, this stepwise scheme of painkilling is effective in most cases. However, 20-30% of patients cannot achieve an acceptable level of pain relief despite the use of these analgesics in combination. Is there another way to help such patients? Interventional methods of analgesia are an option, yet not all patients agree to invasive methods due to the possible side effects and unavailability of these methods. In these cases other mechanisms of analgesia are required, such as NMDA receptor antagonists, which reduce opioid tolerance and hyperalgesia. Still not all the drugs of this group can be applied in our practice.
Analgesic properties of nitrous oxide can only be found in high anesthetic doses. Another option is metadon, but it is forbidden and cannot be used in our country. Still one more option is ketamine, which has severe side effects.
In our clinical practice we decided to use xenon, which has NMDA inhibition effects. Its analgesic effect and safety have been confirmed in numerous studies.
This publication aims to demonstrate a successful clinical case when we used xenon and oxygen inhalations course for the treatment of a severe cancer pain with a patient who had been taking morphine by mouth.

Lung cancer is a leader in the world in terms of morbidity and mortality. Moreover, the number of patients with locally advanced forms of non-small cell lung cancer exceeds 30% of all newly diagnosed cases. The standard of treatment for patients with inoperable stage III lung cancer is chemoradiotherapy. Currently, ways to increase the effectiveness of chemoradiotherapy are being considered, in particular, local escalation of the radiation dose to the tumor, which allows personalizing approaches in the treatment of this category of patients. One of the most common complications of chemoradiotherapy is post-radiation pulmonitis, which requires timely diagnosis and treatment with glucocorticosteroids in severe cases.
We present a case report of a patient with locally advanced non-small cell lung cancer who received treatment as part of simultaneous chemoradiotherapy in the hypofraction mode, complicated by post-radiation pulmonitis.
Successful treatment of complications led to the restoration of the general condition of the patient; during the follow-up examination, a complete response to the specific treatment was recorded.
Thus, a promising method of treating patients with inoperable stage III non-small cell lung cancer is the option of simultaneous chemoradiotherapy with local escalation of the radiation dose to the tumor, while being wary of complications such as pulmonitis, allows for timely diagnosis and treatment of the condition.

Stomach cancer is one of the most frequently diagnosed cancers. The success of special methods of treatment are still disappointing in this disease, and stomach cancer has historically been considered a tumor refractory to treatment. Therefore, this category of patients, especially in the stage of dissemination, in most cases, palliative therapy is recommended. In recent years, the use of systemic chemotherapy and targeted therapy has led to a significant improvement in the quality of life and survival rates for stomach cancer compared to palliative therapy. However, significant progress in diagnostic methods over the past two decades has made it possible and possible to review approaches to the treatment of many cancer diseases that are refractory to chemotherapy. The last 2 decades, due to improved methods of diagnosis have allowed to revise approaches to the treatment of many refractory to chemotherapy of neoplastic diseases. In particular, the literature describes cases of revision and changes due to pre-existing diagnosis of IHC Research (carcinoid, NEO, stomach cancer, pancreatic cancer). This communication allows to share their own long experience of observation and treatment of a patient with a rare form of stomach cancer – lymphoepithelioma-like carcinoma.

Introduction. Nodular goiter is one of the most common endocrine disorder, and thyroid cancer takes a leading place among
malignancy of the endocrine system.
The aim of our study is to evaluate the prevalence and risk factors of thyroid cancer.
Materials and methods: this is a retrospective case-control study that included 140 patients operated with suspected thyroid cancer according to a cytological study of fine needle aspirates in single center in 2018. All patients underwent preoperative cytological examination with interpretation of the results according to the Bethesda system, thyroid ultrasound examination, thyroid status assessment. The results of the cytological examination, as well as clinical and laboratory data were compared with the data of histological analysis.
Results: According to the preoperative cytological study, 76 nodules were reported as Bethesda IV, 4 – Bethesda III, 32 – Bethesda VI, 28 – Bethesda V. According to the results of a histological examination, thyroid cancer was confirmed in 70% of patients: in 89,3% of Bethesda V and 100% in the Bethesda VI group, 52,6% of Bethesda IV, 25% of the Bethesda III. The risk of nodule malignancy was associated with such ultrasound signs as hypoechoicity, calcifications and irregular contours.
Conclusions: the improvement of the methods of preoperative diagnosis of thyroid cancer should help to choose the optimal surgical strategy, reduce the number of diagnostic and repeated thyroidectomy.