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Background. The inclusion of lenvatinib in the immunotherapy regimen for patients with MSS/pMMR endometrial cancer (EC) is due to its ability to modulate the tumor microenvironment, which allows the use of pembrolizumab in low-immunogenic tumors. However, only 30 % of patients with advanced or metastatic EC have a clinical response when treated with pembrolizumab and lenvatinib. In this regard, there is an obvious need to identify biomarkers that allow accurate selection of candidates for this type of therapy.Aim. To determine the predictive value of subpopulations of lymphocytes and macrophages, their expression of PD-1, expression of estrogen receptors, as well as vessel density in immunotargeted therapy for advanced or metastatic EC.Materials and methods. An open-label non-randomized observational association study was performed, involving a total of 22 patients with advanced or metastatic MSS/pMMR EC treated with pembrolizumab and lenvatinib. Duration of clinical effectiveness was used as a parameter to stratify patients. Using TSA-associated multiplex immunofluorescence, the proportions of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes and CD163+macrophages in tumor samples before the start of immunotargeted therapy were analyzed.Results. Three microenvironmental parameters were found to be associated with duration of clinical efficacy: the proportion of CD20+ B cells, the proportion of FoxP3+ T regulatory lymphocytes, and the ratio of CD8+/CD20+ lymphocytes in the tumor microenvironment. However, the CD8+/CD20+ lymphocyte ratio had the greatest predictive value; a value below 3.219 was associated with long clinical efficacy in patients with advanced or metastatic EC.Conclusion. The ratio of cytotoxic and B-lymphocytes in the microenvironment is a reliable predictor marker of the duration of the period of clinical effectiveness of immunotargeting therapy in advanced or metastatic EC.

Background: Cutaneous melanoma is an extremely aggressive disease with an unpredictable prognosis. Even among patients with similar tumor parameters and extent of surgical treatment, survival may vary. The extent of surgical resection of primary cutaneous melanoma is well-established, and a BRAF mutation in the tumor is an unfavorable prognostic factor for patient survival. The mutation presence is mainly used as a marker for prescribing targeted therapy. The impact of the extent of surgery and the method for restoring a tissue defect on survival of patients with similar stages remains unexplored. The impact of the BRAF mutation in the tumor on survival of patients with cutaneous melanoma depending on the surgery method has also not been studied. We analyzed the surgical treatment outcomes of 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) who were found to have the BRAF mutation and underwent different extents of tumor excision with closure of the surgical tissue defect.Objective: To analyze the impact of the BRAF mutation in the tumor on 5-year survival of patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC), depending on the extent of surgery and the method of replacing the tissue defect.Materials and methods: We used data from 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) and assessed their BRAF mutation status, extent of tumor excision, and method of closing the tissue defect. The patients were divided into 2 groups: the main group (wide excision of the tumor and plastic replacement of the tissue defect) and the comparison group (standard margin and linear closure of the tissue defect). After surgery, all the patients underwent tumor analysis for the BRAF p.V600E/K mutation using real-time PCR. DNA was isolated using the cobas® DNA Sample Preparation Kit on a cobas® z 480 analyzer. We used the following statistical methods: frequency analysis, z test to check the equality, and Kaplan-Meier survival analysis and such software as MedCalc 12.5 (1993-2013, MedCalc Software) and SPSS 26 (IBM Corp, 2019, IBM SPSS Statistics for Windows, Armonk, NY, USA). Results: Wide excision of primary cutaneous melanoma (stages 0-IIA and IIB-IIC) was found to increase 5-year progression-free survival in patients with subsequent plastic replacement of the tissue defect compared with patients with standard margin and linear closure of the tissue defect and 5-year overall survival in patients with stage 0-IIA melanoma. In patients with 0-IIA stage melanoma and positive BRAF mutation test results, wide excision with reconstructive and plastic defect closure improved the 5-year progression-free survival. Conclusions: The 5-year progression-free survival and 5-year overall survival increased by 20.9% (P = .005) and 13.0% (P = .031), respectively, in patients who underwent wide excision of primary cutaneous melanoma followed by plastic replacement of the tissue defect compared with patients with standard excision of primary tumors and linear closure of the tissue defect. The 5-year progression-free survival increased by 23.7% (P = .017) in patients with stage IIB-IIC melanoma, regardless of the BRAF mutation. In patients with 0-IIa stage melanoma and positive BRAF mutation test results who underwent wide excision, the 5-year progression-free survival increased by 20.7% (P = .047) compared with patients who underwent tumor excision with a standard margin.

Objective: evaluation of the comparative pharmacoeconomic effectiveness of treatment sequences with prolgolimab as the first line and combination therapy with BRAF/MEK inhibitors as the second line versus a regimen with BRAF/MEK inhibitors as the first line and prolgolimab as the second line in adult patients with metastatic or unresectable cutaneous melanoma.Material and methods. A detailed Markov and decision tree model was developed to allocate patients with metastatic cutaneous melanoma (mCM) with BRAF gene mutation (BRAF+) to treatment with prolgolimab or to targeted therapy with BRAF/MEK inhibitors (“dabrafenib + trametinib”, or “vemurafenib + cobimetinib” combinations). The costs of BRAF+ mCM therapy and the number of life years gained (LYGs) depending on the treatment regimen were calculated using approximated overall survival (OS) and progression-free survival (PFS) curves taken from relevant publications.Results. The treatment sequence for BRAF+ mCM had a significant impact on patient treatment outcomes: the median OS for the “prolgolimab → BRAF/MEK inhibitors” regimen was 41 months, while for the “BRAF/MEK inhibitors → prolgolimab” regimen it was 26 months; the median PFS was 11.5 months for the sequence starting with prolgolimab and 12.2 months for the strategy starting with “dabrafenib + trametinib” combination. The number of LYGs for a therapy regimen starting with prolgolimab and a regimen starting with “dabrafenib + trametinib” combination when modeling in the 1st year of therapy was 0.92 and 0.94 years, and at a 5-year horizon it was 3.19 and 2.75 years, respectively. At the same time, the cost of 1 LYG with a strategy starting with prolgolimab was 156 thousand rubles (5%) lower than the strategy starting with “dabrafenib + trametinib” combination.Conclusion. The developed pharmacoeconomic research model facilitated a clinical and economic analysis of using prolgolimab compared to targeted therapy with BRAF/MEK inhibitors across four lines of therapy, closely reflecting real clinical practice in the treatment of BRAF+ mCM patients.

Aim. To examine the role of very good partial response or better (VGPR+) as a surrogate predictor of progression-free survival (PFS) in multiple myeloma (MM) patients.Materials and methods. A systematic literature review of MEDLINE database (2010–2023) and materials presented at hematology and cancer congresses (2020–2022) was performed to identify studies reporting median progressionfree survival (PFS) and the rate of very good partial response (VGPR+). The study used Spearman’s weighted correlation and linear regression methods to analyze the association between median PFS and VGPR+. A total of 34,443 patients were involved in 182 original studies that included real-world clinical practice data.Results. Based on the number of patients or year of publication, the correlation between VGPR+ and median PFS was statistically significant (Spearman coefficient r = 0.61), but low. For refractory/recurrent MM (r = 0.69) and for monoclonal antibody therapy (r = 0.81), the correlation between VGPR+ and PFS was stronger. In addition to achieving VGPR+, the line of therapy and autologous stem cell transplantation also played an important role in determining PFS. Based on these factors, an increase of one percentage point in VGPR+ predicted a 0.21‑month increase in median PFS in the final adjusted linear regression model.Conclusion. In this study, VGPR+ was found to predict PFS, making it a universal early point of reference for MM prognosis regardless of the treatment type.

Background. Endometrial cancer (EC) is one of the most significant oncogynecological problems. The main mortality cause in this disease, as in the case of other malignant neoplasms, is the tumor progression. The presence of mutations associated with mismatch repair-deficient is of great prognostic importance. Immunotargeting therapy (ITT), lenvatinib in combination with pembrolizumab, seems to be the most effective solution in the second line treatment of advanced EC without microsatellite instability. At the same time, the group of such patients is heterogeneous in terms of progression-free survival (PFS) on ITT. So that it determines the continuing need to search for reliable parameters steadily associated with the PFS duration in this type of treatment.Aim. To analyze the clinical and morphological features in patients with advanced EC depending on the PFS duration on ITT. Materials and methods. The study included data on patients (n = 36) with advanced EC who received ITT in oncological dispensaries in Siberia and the Russian Far East. The overall patients’ group was analyzed using the Kaplan-Meier method. PFS was defined as the time from the ITT initiation until progression or death against the background of treatment. The influence of the selected factors (clinical and morphological parameters, treatment features, and adverse events) on PFS was assessed using a log-rank criterion. The study participants were then divided into 2 subgroups (15 women and 9 women) according to median PFS. Mann–Whitney tests for independent samples (quantitative measures), and Fisher’s tests (qualitative measures) were used to identify significant differences in comparison subgroups for the selected factors. Differences were considered statistically significant when the significance level was reached (p

Aim to study the frequency of BRCA1/2 gene mutations , the efficacy of ovarian cancer therapy depending on the presence of BRCA1/2 mutations as well as the efficacy of olaparib maintenance therapy in BRCAassociated ovarian cancer.Material and Methods. The retrospective analysis included 355 patients with high-grade, stage I–IV serous ovarian cancer. The examination for a mutation in the BRCA1/2 gene was carried out within the framework of the program “Improvement of molecular genetic diagnostics in the Russian Federation in order to increase the effectiveness of antitumor treatment”.Results. Mutations in the BRCA1/2 genes were detected in 98 out of 355 (27.6 %) patients. Mutations of the BRCA1+ gene were detected in 62 out of 230 patients with ovarian cancer of stages IIIC–IV (27.0 %), the BRCA2 gene – in 9 out of 230 (3.9 %). In ovarian cancer of stages III–IV, BRCA gene mutations were absent in 159 of 230 (69.1 %) patients. The median time to progression in stages III–IV of the disease with a mutation in the BRCA1 gene was 22.0 months, in the BRCA2 gene – 27.0 months, in patients without mutations in the BRCA1/2 genes – 17.0 months, median life expectancy – 70.0; 65.0 and 45.0 months, respectively. Patients with serous ovarian carcinoma of high-grade I–IV stages with the presence of mutations in the BRCA1/2 genes were divided into two groups. The first group (6 out of 26 patients, 23.1 %) consisted of patients with stage IIIC–IV high-grade serous ovarian carcinoma, who received olaparib as maintenance therapy after the 1st line of chemotherapy, the second group (20 out of 26 patients, 76.9 %) were patients with stage I–IV high-grade serous ovarian carcinoma, who received olaparib in maintenance mode after 2 or more lines of chemotherapy.Conclusion. The presence of BRCA1/2 gene mutations significantly increased the median life expectancy of patients with stage IIIC–IV serous ovarian cancer, and primary cytoreduction significantly improved both overall survival and survival to progression in this group of patients. Maintenance therapy with olaparib is more appropriate after the 1st line of treatment than after subsequent ones.

Relevance. The inflammatory process and endogenous intoxication of the patient’s body has a negative impact on the course of many malignant neoplasms, including salivary gland cancer.The objective of the study was to determine the influence of some factors of systemic inflammation and endogenous intoxication in salivary gland cancer.Methods and materials. A prospective study included the data of 59 patients with salivary gland cancer. The influence of peripheral blood parameters and relative indicators characterizing systemic inflammation on overall and disease-free survival was assessed.Results. As a result of the multivariate analysis, it was revealed that an increase in the level of the relative number of peripheral blood neutrophils by more than 60.08 % increases the risk of death in patients from salivary gland cancer by 3.90 times (p=0.0456; HR 3.90: 95 % CI 1.03–14.79). The level of the absolute number of peripheral blood lymphocytes, not exceeding 1.49x109 /l, increases the risk of disease progression by 8.72 times (p=0.0002, R 8.72: 95 % CI 2.78–27.28).Conclusion. Individual factors of systemic inflammation and endogenous intoxication, it is advisable to evaluate at the stage of planning the primary treatment of patients with salivary gland cancer, in order to determine the prognosis of the disease and optimize the choice of tactics for the primary treatment of patients.

Aim. The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. Materials and methods. The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. Results. The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. Conclusion. The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.

Background. Over the past 10–15 years, there has been a clearer understanding of the processes occurring in cells of the primary glioblastoma. However, the change in MGMT gene expression and its role after disease relapse remain understudied. Purpose: to study changes in MGMT gene expression in case of recurrent primary glioblastoma after the standard therapy; to determine influence of clinical factors and MGMt gene expression on relapse-free survival of patients. Materials and Methods. We carried out a prospective analysis of clinical and molecular genetic characteristics of 21 patients aged from 28 to 63 with primary glioblastoma before and after recurrence. Relative mRna expression of MGMT gene and mutations in IDH1/IDH2 genes were determined in surgical biopsies using PCR techniques. after the first surgery, all patients received radiation therapy (60 Gy) and chemotherapy with adjuvant temozolomide (2–18 cycles). the second-line chemotherapy was performed in 17 (80.9 %) patients, and 8 patients received (47 %, 8/17) temozolomide.Results. the relationship between the progression-free survival (PFs) and mRna expression of MGMT gene (73.5 vs 33 weeks, p=0.013) and objective response to therapy (88 vs 36 weeks, p=0.046) was found. The number of cycles of first-line chemotherapy with temozolomide influenced the duration of the first PFs (65 weeks vs 21.5 weeks, p=0,07). the first PFs was not affected by patients’ age (p=0.64), sex (p=0.17), Karnofsky performance scale index (p=0.43), extent of brain damage (p=0.41) and extent of the resection (p=0.27). after onset of relapse, mRna expression of MGMT gene remained the same, being 66.7 % (14/21). The increased expression was observed in 23.8 % (5/21) of cases, and decreased gene expression was observed in 9.5 % (2/21) of cases. the second PFs was affected by the extent of tumor resection, although there were no statistically significant differences (p=0.52). the effect of mRna expression of MGMT gene on the median second PFs was not revealed (p=0.39). no objective response to therapy was found in patients with a low mRna expression of MGMT gene. Conclusion. Recurrent glioblastoma becomes more resistant to further therapy. With the development of tumor recurrence, the predictive value of MGMT gene is lost and the role of the extent of cytoreductive surgery increases.

This article presents a systematic literature review to assess the survival outcomes of patients with bilateral renal cell carcinoma who underwent nephro-preserving surgery. Patients with bilateral renal neoplastic lesions represent a rare subpopulation, numbering, according to different authors, from 2 to 6 % of the total RCC group. Despite the increase in the number of cases of bilateral RCC, the number of works devoted to the study of the features of surgical intervention, prognosis factors, treatment outcomes and survival of this cohort of patients is limited, and a number of important questions regarding this problem remain unresolved. Currently, the only effective method of treating bilateral renal cancer is nephro-preserving surgery in the volume of bilateral renal resection / nephrectomy with resection of the contralateral kidney in case of synchronous lesion or resection of a single kidney in case of metachronous lesion. This strategy avoids or reduces the risk of developing renal failure and its consequences after surgery. Conclusion. Nephro-preserving surgery for bilateral renal cell carcinoma is the only effective method to achieve satisfactory oncological results with a low incidence of complications.

Aim. The main aim of this study was to model the effectiveness of multiple myeloma (MM) therapy using machine learning, which was based on the analysis of various methods of MM treatment, a number of prognostic factors and their results in the daily routine clinical practice of medical centers in European countries. Materials and methods. The present study was retrospective, non-interventional, multicenter. A structured database of MM patients provided by the Oncology Information service (O.I.s.) was used for the study. Registration took place in medical institutions in eight countries: Austria, Belgium, Switzerland, Germany, Spain, France, Greece and Great Britain. Results. In total, 57% of men and 43% of women were analyzed in the base of 6074 patients with MM. The median age was 71 years. The median follow-up time along the lines was 387 days. High-risk cytogenetics are represented in 15% of cases. The efficacy endpoint was the best response to each line of therapy, as measured by time to death (TTD) as an indirect indicator of overall survival and time to next treatment (TTNT) as an indirect indicator of progression-free survival. The median TTD and TTNT were 730 and 399 days respectively. After a multi-step selection process, characteristics with the greatest importance for the therapy prognosis were selected: age at the beginning of therapy, line of therapy, time after MM verification, ECOG (Eastern Cooperative Oncology Group), cytogenetic risk, transplant eligibible or not, TTNT after the previous line of therapy, therapy regimen. Discussion. To continue the study it is necessary to analyze literature data and compare with real practice. Also analysis and comparison with Russian data on the treatment of patients with MM is required. Conclusion. The analysis of the presented data provides a basis for modeling a tool for assessing the effectiveness of MM therapy (prognosis of TTD and TTNT) for each patient, based on a number of prognostic factors and the results of routine clinical practice in various medical centers in European countries.

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

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.

Introduction. The term “local recurrence” is usually understood as regrowth of a tumor after surgical treatment. The regrowth appears within 3–5 cm from postoperative cicatrix. The causes for such prolonged tumor growth or recurrence of patients with cutaneous melanoma are nonradical surgical treatment as well as satellite or transit metastases that were not removed in-block with primary tumor. A great number of clinical researches, aimed at examination of melanoma, its patterns, anatomical criteria and features of clinical course, gave an opportunity to separate satellite or transit metastases into an independent group. Such metastases are realized inside or subdermally, up to 2 cm or more than 2 cm from the primary tumor, yet, not reaching the location of the first regional barrier.The aim of the study is to define influence of the main prognostic factors such as tumor thickness according to Breslow, the level of invasion according to Clark and the presence of ulceration on the frequency of local recurrence with cutaneous melanoma of head and neck.Materials and methods. The research involved 174 patients with cutaneous melanoma of head and neck (1995–2014). According to our index of contraction of a skin flap (median 30 %) the true borders of resection were clearly defined within all the patients. Thereby, 3 groups were identified with the following resection margin: 1.0 cm, where followed-up treatment results were analyzed.Results. Progression-free survival didn’t correlate with the size of surgical resection margins. The survival rates were the best with the lowest resection margin under 0.5 cm (77.3 %) and the worst with the highest resection margin more then 1.0 cm (38.7 %). That means that the treatment results don’t depend on the width increase of tumor resection margin.Conclusions. We consider that clear surgical margins for any thickness of cutaneous melanoma of head and neck should be as follows: 4 mm – 0.72 mm (p = 0.016). In our work, the influence of the main prognostic factors, such as tumor thickness according to Breslow, level of invasion according to Clark and ulceration on the frequency of head and neck cutaneous melanoma local recurrences had no impact.

Ovarian cancer is one of the most common cancers in women. Growth and extension of the tumor are associated with active neoangiogenesis regulated by vascular endothelial growth factor (VEGF). Bevacizumab decreases VEGF activity and inhibits the tumor growth.Purpose of the study. The aim of the study was to evaluate results of bevacizumab in maintenance therapy for ovarian cancer.Materials and methods. 26 patients with ovarian cancer received maintenance therapy with drop infusions of bevacizumab 15 mg/kg once a day for 21 days in 2014–2019 after completing chemotherapy for relapses.Results. Bevacizumab mainterned partial response or stabilization in 76.9% of patients. The adverse events were mainly of grades 1–2 (in 88.5% of all adverse events) and could be managed by an appropriate medical correction. Hemorrhagic complications caused the cancellation of bevacizumab in one patient.Conclusions. Bevacizumab in maintenance therapy after completing chemotherapy for ovarian cancer relapses (both platinum-sensitive and platinum-resistant) significantly improves the treatment results. The toxicity profile of bevacizumab in maintenance treatment is acceptable.

It is known that currently PARP inhibitors are actively used in the treatment of tumors of the female reproductive system. A large number of studies have been presented demonstrating the effectiveness of PARP inhibitors in the treatment of BRCA-associated ovarian cancer. It was found that mutations in the BRCA1 and BRCA2 genes are also characteristic of breast cancer (BC). However, PARP inhibitors are rarely used in clinical practice in the treatment of BC. So far, only olaparib has become the first PARP inhibitor approved for the treatment of metastatic BC. This review presents data over the past ten years showing the high efficiency of PARP inhibitors in the treatment of malignant neoplasms of the mammary gland. In 7 of 28 studies analyzed, positive results were achieved with combined treatment with chemotherapeutic drugs and PARP inhibitors. So, for example, in two studies in the treatment of BRCA-associated BC, the response to treatment in patients was 72.5–73.2 %. Thus, PARP inhibitors are of great interest and are of practical value in the treatment of patients with BC.

Background. The implementation of tyrosine kinase inhibitors into clinical practice improved treatment outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Lenvatinib is recommended as a first-line drug for these patients. The study objective is to analyze clinical experience with lenvatinib in patients with RR-DTC in the Russian Federation. Materials and methods. The data from 18 clinical sites in Russia was analyzed for the period December 2015 and September 2019. Seventyseven patients with histologically verified DTC, proven resistance to radioactive iodine therapy, and tumor progression (according to the Response Evaluation Criteria In Solid Tumors 1.1 criteria) were included in the study. Results.Median progression-free survival in patients included into analysis (n = 72) was 26.1 months. In patients who responded to therapy (including those with partial and complete response), median progression-free survival reached 36.2 months, which is higher than that reported in the updated results of the SELECT study (33.1 months). Lenvatinib-associated adverse events (AEs) were observed in 87 % of patients. Severe AEs were registered in 18.2 % of participants. In 6.5 % of cases, AEs lead to lenvatinib cessation; in 74 % of cases, AEs required dose reduction.Conclusion. Our findings suggest high efficacy and good tolerability of lenvatinib in patients with RR-DTC in routine clinical practice in the Russian Federation.

The aim is to develop a generalized algorithm and methodology for conducting clinical and economic studies (CeS) on medications used in treatment of malignant neoplasms (MnP). Materials and methods. We conducted a literature search and then reviewed the recent reports on similar CeS. In so doing, we paid special attention to the model type, the modeling methodology, information on the effectiveness and cost, the cost elements, performance criteria, the assessment of the CeS final results, as well as the possibility of applying these results to the national healthcare system. We used the methods of generalization, systematization, as well as visual-graphical and mathematical modeling. Results. A general algorithm for conducting a pharmacoeconomic study has been proposed; this includes an effectiveness analysis, a cost analysis and a comparison of costs and effectiveness (cost-effectiveness). The effectiveness analysis includes selection, digitization, and approximation of overall survival (OS) and progression-free survival (PFS) curves followed by their extrapolation. The choice of extrapolation method is discussed. The cost analysis includes calculating the cost of medications in question, the costs associated with the indicated therapy and with adverse events (Ae), as well the costs associated with disease progression (for certain drugs). The possibility of analyzing indirect and non-medical costs is also discussed. A dynamic version of the Markov model pertaining to the first order course of a disease is proposed; this includes the status before progression (first-line therapy), after progression (second-line therapy) and death. Considering the succession of treatments and the availability of additional data, a similar second-order model (and subsequent orders) can be applied to incorporate additional patient’s condition after the first progression to the second progression (second-line therapy) and after the second progression (third-line therapy). Conclusion. A generalized algorithm has been developed and proposed for carrying out CeS of medications used in MnP.

Chemotherapy is among the primary methods of treating advanced breast cancer. It was shown that clinical efficacy of various chemotherapeutic agents in many cases depends not only on their direct cytostatic and/or cytotoxic effect upon tumor cells, but also on their ability to modulate phenotype of the tumor cells and to influence anti-tumor immune response. Initial state of the immune system and its response to treatment is crucial. Antitumor response involves cells of innate and adaptive immunity (NK, NKT, T cells). These populations are heterogeneous and contain, e.g., cells with antitumor activity and regulatory (suppressor) cells that suppress immune response and promote tumor progression. The aim of this work was to determine the relationship between the initial state of cellular immunity of patients suffering from locally advanced breast cancer with triple negative phenotype, and clinical effect of chemotherapy (cisplatin + doxorubicin/paclitaxel), and studying effects of the therapy upon subpopulation profiles of peripheral blood lymphocytes in the patients. We registered the terms of the disease progression as well as overall survival and progression-free survival. The disease progressed in 25 of 53 cases (47.2%) whereas 28 of 53 patients (52.8%) remained progression-free. The observation period was 35.5 months. Laboratory examination of the patients included immunophenotyping of peripheral blood lymphocytes and determination of NK cell cytotoxic activity before and after chemotherapy. Percentages of effectors and regulatory lymphocyte populations were determined. The results obtained showed that, for some lymphocyte subsets, the pre-treatment differences of cell percentage deviations from control were found between the progression-free groups and patients with progression of the disease. The differences in percentages of NKT cells and lymphocytes expressing CD25 activation marker proved to be most significant. Decreased number of NKT cells and activated CD25+ lymphocytes prior to chemotherapy was associated with increased probability of disease progression. Reduced percentage of NKT cells against control was observed in 56% of patients from the progression group (PD), and only 21.4% in the group free of disease progression (DF). [OR = 4.6 (95% CI 1.4 to 15.4)]. Percentage of CD25+ lymphocytes was decreased from 68.2% in the PD group, and 28.6% for DF patients [OR = 5.4 (95% CI 1.6-18.1)]. We studied relationships between the overall survival (OS) and percentage of perforin-containing NK, NKT, and T cells, and mean perforin fluorescence density (PFD) in these lymphocyte subsets in 26 of the 53 patients before treatment. A statistically significant positive correlation was revealed between OS and perforin PFD in all the three cell populations under study. Normalization of the parameters altered before treatment, and an increase of T cell numbers was observed in the disease-free patients.

Objective: to study the prognostic significance of the expression of cancer-testis (CT) genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in patients with multiple myeloma (MM) and their influence on overall survival and relapse rate. To determine their effect on suсh clinical parameters as levels of lactate dehydrogenase, leucocytes, hemoglobin, calcium, albumen, creatinine, beta-2-microglobulin.Materials and methods. Real-time polymerase chain reaction was performed on complementary DNA obtained from bone marrow of 77 patients with MM. The statistical analysis was performed using the Statistica 10.0 software package. To estimate prognostic values of the CT gene expression data were analyzed by the Kaplan – Meier method.Results. The study was conducted to determine the level of expression of CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in a group of patients with MM. The group included primary and receiving cancer treatment in MM patients. According to the log-rank criterion expression of any of the CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 exerts a significant influence on overall survival and progression-free survival/relapse. It was also determined that providing expression of some CT genes, the levels of creatinine, calcium, beta-2-microglobulin were much higher to compare with patients without expression.

The review considers information about the efficacy and safety of Ixabepilone as a monotherapy and as a component of combination therapy for advanced breast cancer. Successful treatment of metastatic breast cancer is often confounded by resistance to chemotherapy, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially important. A therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer and “intensivelytreated” variant. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease.

Objective: to evaluate tolerability and efficacy of maintenance treatment in the absence of progression after 16 weeks of first-line therapy in patients with unresectable metastatic colon cancer.Materials and methods. We have analyzed medical case histories of patients with metastatic colorectal cancer who underwent treatment in the department of clinical pharmacology and chemotherapy of N. N. Blokhin Russian Cancer Research Center from 2007 to 2015 years. Inclusion criteria were the following: 16–24 weeks of first-line chemotherapy with no signs of progression and the inability to perform metastasectomy. Progression-free survival was the main criterion for effectiveness in our study.Results. 160 (44.5 %) of 359 treated patients met the inclusion criteria. 102 (63.7 %) patients were followed up, while the other 58 (36.3 % – comparison group) patients underwent maintenance chemotherapy. Grade I–II toxic reactions and grade III complications associated with first-line chemotherapy were insignificantly more common in the group of patients left on maintenance chemotherapy: 72.4 % and 37.9 % versus 57.8 % and 24.5 % in the comparison group, p = 0.07 and p = 0.07 respectively. The frequency of grade I–II toxic reactions and grade III complications in the second-line treatment did not differ between treatment groups (p = 0.9 and p = 0.8). The median of progression-free survival in observation group and comparison group was 4, and 6 months (odds ratio (OR) 0.6; p = 0.009), and life expectancy – 23 and 31 months (OR 0.75; p = 0.1), respectively. Statistically significant differences between groups with respect to achieving the objective response and/or normalization of carcinoembryonic antigen level were revealed: median of progression-free survival was 13 (n = 26 of 57; 45.6 %) and 4 months (n = 31 of 57, 54.4 %), respectively (HR 0.38; p = 0.002), median of life expectancy – 34 months versus 26 months (OR 0.37; p = 0.3). Conclusions. Carrying out maintenance therapy is associated with increased incidence of grade III complications during the first-line treatment, but does not affect the tolerability of the second-line treatment. Supportive chemotherapy with fluoropyrimidines remains to be the most effective in patients with favorable prognostic factors such as normalization of carcinoembryonic antigen and/or achievement of the objective response on the background of first-line chemotherapy.

Background. Objectives: analysis of the most important prognostic factors for progression-free survival (PFS) in patients with low-grade cerebral gliomas (LGG). material and methods. 107 patients with morphologically proven low-grade cerebral gliomas were included into the study. There were 57 (53.3 %) patients with diffuse astrocytoma, 14 (13.1 %) with oligoastrocytoma and 36 (33.6 %) patients with oligodendroglioma. Results. Risk factors included age ≥40 years, diffuse astrocytoma, tumor size of more than 6 cm, displacement of the midbrain structures and severe or moderate neurological deficit. Acute cerebral circulatory disorder and the extent of surgical excision of the tumor did not effect on the outcome of LGG treatment. The highest rates of PFS were observed in patients with stage T3 disease and the lowest PFS rates in patients with stage III disease. Conclusion. Significant risk factors should be considered in planning multi-modality treatment for low grade cerebral gliomas.