Aim . To assess the efficacy and safety of lenvatinib and pembrolizumab for the treatment of mismatch repair-proficient endometrial cancer (EC) in routine clinical practice in Russia. Materials and methods . This multicenter, retrospective, cohort study included patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between May 2020 and April 2023. Patients with histologically verified EC without microsatellite instability who received ≥1 course of pembrolizumab/lenvatinib therapy were included in the study. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed, the objective response rate and the toxicity profile of therapy were assessed. Results . The study included 100 patients. Median age was 65 (30–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (68 %); serous adenocarcinoma was diagnosed in 22 % of cases, other types of tumor – 10 % of cases. All patients had pMMR/microsatellite-stable tumors. The median progression-free survival was 7.75 months (95 % confidence interval 0.7–33.8), and a partial response to therapy was observed in 24 % of patients. Almost half of the patients (44 %) required dose reduction due to adverse events. The most common adverse events included fatigue (n = 26; 26 %), hypertension (n = 20; 20 %), and hypothyroidism (n = 14; 14 %). Conclusion . This study confirms the clinical efficacy of lenvatinib and pembrolizumab in patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR-tumors) in routine clinical practice.

Background. Endometrial cancer (EC) treatment outcomes need to be improved. Immunotargeted therapy lead to long-term and delayed effects compared to chemotherapy. Estimation of long-term efficacy and quality of life are crucial when we are talking about efficacy in whole.Aim. To evaluate the long-term clinical efficacy of lenvatinib plus pembrolizumab therapy in patients with EC.Materials and methods. The study included 43 patients with stages I-IV EC with mismatch repair-proficient tumors and treatment duration of more than 9 months. We evaluated median progression-free survival, objective response, duration of treatment depending on the line of therapy, prevalence and type of adverse events, and correction regimens. Results. Lenvatinib plus pembrolizumab treatment was safe and efficacious in recurrent EC. Median of progression-free survival (patients with response or stabilization more than 9 months) is 10.2 months (95 % confidence interval 9.1-13.0), median of follow up is 9.7 (1.4-33.8) months. There were no complete responses, partial response was in 12 (28 %) patients, disease stabilization was in 31 (72 %) patients. Regarding safety, the overall rate of any-grade adverse events was 56.3 %. The most common treatment-related adverse events were fatigue (32.6 %), hypertension (23.3 %), and hypothyroidism (18.6 %). Dose reduction was performed in 22 (51.2 %) patients.Conclusion. The combination of lenvatinib plus pembrolizumab has long-term efficacy and manageable profile of safety. The presence of a significant pool of patients with durable response allows improving the survival rate of such patients in Russia.

Introduction. Neoadjuvant endocrine therapy (NET) is an effective treatment modality that can downsize breast tumors in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. A lack of data regarding efficacy of NET vs neoadjuvant cytotoxic chemotherapy (NCT) leads to limited usage of NET despite its favorable toxicity profile. Perioperative endocrine therapy is mainly used for the elderly or patients with comorbidities that limit their access to NCT. The COVID-19 pandemic led to increased data of NET efficacy. Nevertheless, long-term outcomes of NET application are underrepresented in literature. Objective. Assessment of long-term outcomes in patients treated with neoadjuvant endocrine therapy (NAT) versus neoadjuvant cytotoxic chemotherapy in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. Materials and methods. We retrospectively evaluated the results of treatment of 154postmenopausal patients with luminal HER2-breast cancer who were treated with neoadjuvant systemic therapy (NET or NCT) at the State Medical Institution «St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)» from 01.01.2019 to 31.11.2020. We analyzed data on radiological, pathomorphological and long-term treatment outcomes (rate of locoregional and overall recurrence) in two groups.Results. 154 patients received neoadjuvant hormone therapy (n=78) or neoadjuvant chemotherapy (n=76). The clinical response was evaluated according to the RECIST criteria after 12 weeks and after study treatment using MMG. Partial or complete radiological response was achieved in 41.0% (n=32) in the NET group vs 69.7% (n=53) in the NCT group (p<0.001). All patients included in the study underwent surgery. A complete pathologic response was observed in 9.2% (n=7) of patients in the chemotherapy group, and in 0% of patients in the endocrine therapy group (p=0.006). Median follow-up was 46.2 months. Progression was recorded in 23.2% (n=29) of participants, with no significant benefit of NCT over NET in the frequency of locoregional relapses (NET n=8 (10.3%) vs NCT n=4 (5.3%)) (p= 0.369) or the occurrence of distant metastases NAT n=8 (10.3%) vs NCT n=13 (17.1%)) (p=0.216). Multivariate analysis showed that only pathologic lymph node status (ypN2–3) was an independent predictor of progression (p=0.007, OR=3.2; 95%CI: 1.380-7.422). Conclusions. Long-term outcomes after neoadjuvant hormone therapy are comparable with chemotherapy in the group of postmenopausal women with luminal HER2-breast cancer. The small sample size and limited follow-up period are significant limitations of our work.

Aim of the study. Analysis of the efficiency of the central chemotherapy drugs breeding department in the medical institution of oncological profile using the example of «St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncological) named after N.P. Napalkov». Materials and Methods. The study assesses the performance of the central chemotherapy drugs breeding department by assessing the database established in the department, using the example of «St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncological) named after N.P. Napalkov». Results and discussion. As a result of the analysis, it was determined that the centralization of the of chemotherapy drugs breeding allows to increase the safety of staff and patients, reduce the burden on nurses of departments, provide additional control of drugs dilution (sterility and quality of the finished solution, accuracy of dosing) and to save 10% of the cost of purchasing medicines (during the analyzed period it was 808 million rubles), relatively to decentralized dilution, while maintaining the amount of medical care and even increasing the possible amount of high-priced medical care. The need to create a regulatory framework and also the need to assess the quality of prepared solutions was identified. Conclusion. The establishment of a central chemotherapy drugs breeding department is an example of the rational use of medicines. Experience of work of the GBUZ «St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncological) named after N.P. Napalkov» should be analyzed and implemented in other medical institutions to optimize the work with cytostatic drugs

Administration of the required symptomatic and palliative care in oncology allows not only to provide a higher quality of life for patients, but also to some extent improve oncological results. This review article provides an analysis of data on the incidence and main mechanisms of athogenesis of various types of emetogenic toxicity in patients receiving anticancer treatment, provides an overview of existing recommendations for the prevention of nausea and vomiting, and discusses some practical aspects of antiemetic treatment. In addition, this article discusses the main algorithms for the treatment of chronic pain in oncology, analyzes some aspects of the use of analgesics in clinical practice, taking into account current recommendations, and provides examples of interventional analgesic techniques.

IMPORTANCE. Neoadjuvant endocrine therapy (NET), despite demonstrating comparable data to neoadjuvant chemotherapy (NACT) in regard to ORR and being a less toxic alternative, is still used in clinical practice mainly for elderly patients or those who are not good candidates for chemotherapy. The COVID-19 pandemic led to increased application of NET for patients with HR-positive/HER2-negative breast cancer, that showed a growing need for data evaluating its efficacy in terms of long-term outcomes of treatment and for examining potential predictive biomarkers. OBSERVATIONS. We provide readers with a critical in-depth review on landmark trials comparing NET with NCT in HR-positive/ HER2-negative breast cancer. This also includes an overview of potential predictive biomarkers for identifying subsets of HR-positive breast cancer that could be safely spared neoadjuvant chemotherapy. CONCLUSIONS AND RELEVANCE. NET is an effective treatment modality for postmenopausal women diagnosed with HR-positive/ HER2-negative cancer that can downsize breast tumors. Due to the absence of large RCT comparing NET with NCT, little data on long-term outcomes, deep analysis of clinical practice treatment results is needed. Further research on potential predictive biomarkers and their validation is an important clinical issue.

Background.BRCA1/2 germline testing allows us to optimize treatment strategy for patients with breast and ovarian cancer cases,to provide early diagnosis and also prophylactic measures for mutation carriers. Considering absence of large BRCA studies on Russian population, we do not have any clear understanding of approximate BRCA1/2 germline mutation frequency, a whole number of founder mutations and impact of non-founder BRCA1/2 mutations, which are not included in a standard PCR panel. Objective. Assessment of the frequency of BRCA1/2 mutations detection by means of PCR in breast and ovarian cancer patients in real clinical practice in St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (oncological) named after N.P. Napalkov. Analysis of a database for BRCA1/2-negative patients on a presence of risk factors associated with a probability of carrying a germline mutation in BRCA1/2 genes. Materials and methods. We retrospectively evaluated 335 ovarian and 1196 breast cancer patients, tested for germline BRCA1/2 by PCR in SPb CSPC(o) named after N.P. Napalkov from 01.01.2019 to 31.12.2021. For analysis was used patient’s blood plasma and a standard PCR panel detecting 8 mutation variants. A database for BRCA1/2-negative patients was retrospectively analyzed on a presence of risk factors associated with a high probability of hereditary cancer: an early onset and family history of cancer (BRCA associated). Statistical analysis was carried out using the SPSS software package (IBM® SPPS® Statistics v. 20), a number of graphs were carried out using Microsoft® Excel® 2016 programs. Results. BRCA1/2 germline mutations were detected in 6,4% (n= 98). Mean frequency of detection was 12,6% (n=45) for ovarian cancer patients, 4,3% (n=53) for breast cancer patients. Analysis of a database for BRCA1/2-negative patients demonstrated that 22,5% (n=346) BC and OC cases had an early onset. Family history of cancer was identified for 13,6% (n=195) patients with breast or ovarian cancer, including 3,8% (n=43) with 2 and more family cases of BRCA associated cancers. Conclusions. The frequency of detected BRCA1/2 germline mutations by PCR for breast and ovarian cancer patients in SPb CSPC(o) named after N.P. Napalkov is lower than the one described in international data. A large part of patients BRCA1/2 negative by PCR test has characteristics of hereditary breast cancer syndrome and requires further NGS.

The huge global burden of oncological diseases is growing and measures to counter this complex challenge are high on national health agendas. The Russian National Long-Term Oncology Strategy 2030 defines priorities, goals and directions in the fight against cancer. Italso contains action plans for more effective prevention, earlier and more specific diagnosis and more effective treatment options. Against this backdrop, experts now suggest to complement standard oncology treatment strategies by adding Patient Blood Management (PBM). For many clinical disciplines where a low blood count and considerable blood loss are commonly encountered, this bundle of care is the new standard. Based on clinical and scientific evidence, it aims to optimise medical and surgical patient outcomes by clinically managing and preserving a patients blood. The principles of this comprehensive concept can and must be transferred to oncology, thus offering value in improving cancer care and the efficacy of medical institutions. Accumulating evidence demonstrates that anaemia and iron deficiency, but also thrombocytopenia, blood loss and coagulopathy are independent risk factors for adverse patient outcomes including morbidity, mortality, reduced quality of life and prolonged average length of hospital stay in both surgical and medical patients. For the timely and effective detection and correction of these risk factors, an international network of multi-disciplinary clinicians and researchers has developed PBM. The rapidly growing body of evidence for PBM not only shows improved patient outcomes, but also reduced resource utilisation including the use of allogeneic blood components. The reduction of allogeneic blood transfusion further improves patient safety and outcomes, since transfusion is another independent risk factor for adverse outcomes. Supported by WHO endorsements and following the recommendations of an increasing number of state or national health authorities, PBM is about to become a new standard of care. However, even though the aforementioned risk factors are highly prevalent in oncology settings due to chemo-/radiotherapy and the pathology of the disease, the integration of PBM in standard oncology treatment pathways is lagging behind. Thus, and in support of the Russian National Long-Term Oncology Strategy 2030 to improve quality of oncological care, with the support of the National Association of Specialists in PBM (NASPBM), the PBM Oncology Working Group of the Russian Federation was created, consisting of national and international experts in oncology and PBM. On July 9, 2020, the Working Group met to discuss the rationale for PBM in oncology and to assess the need to implement PBM in Russian oncology care. As a result, the Group recommended to include PBM as an integral part of standard oncology treatment pathways, delineated the action required from facilitating stakeholders in the Russian Federation, determined a roadmap for implementation and developed a national resolution as a call to action on the matter. Presented herein, this resolution acknowledges the global and local impetus to reduce cancer mortality, and the rationale for PBM interventions to improve patient outcomes and alleviate the social and economic burden of cancer on the healthcare system.

INTRODUCTION. Intrathoracic esophageal postoperative suture’s failure occurs in 8–26 % after distal esophagectomy and 3–12 % after total gastrectomy, also this leads to the development of life-threatening complications and a rather high mortality rate. Endoscopic vacuum therapy is an actively developing and modern method of treating defects in the wall of hollow organs.CINICAL EXAMPLE. 9-year-old patient had resection of the esophageal wall for an enterogenic cyst. The failure of the postoperative suture was clinically diagnosed after the 1st day of operation, confirmed by endoscopic and X-ray findings. We decided to use endoscopic vacuum therapy with Suprasorb sponge. The sponge was replaced at intervals of 3–5 days. On the 9th twenty-four hours after the operation, a delimited cavity into the mediastinal pleural space with a length of 8 cm and a width 1.5 cm with fibrin deposits on the walls was diagnosed. The size and shape of the sponge depended on the size of the defect of the esophageal wall and the volume of the delimited cavity. Conservative and rehabilitation therapy was also carried out. On the 40th day after the operation, complete epithelialization of the esophageal wall defect was noted. The patient was discharged in a satisfactory condition. Due to the results of our clinical observation, we reached a conclusion that endoscopic vacuum therapy is applicable in clinical practice, because it is an effective method of treatment for the of intra-thoracic esophageal suture’s failure. The technique is relatively safe, contributes to the complete elimination of the full-wall defect, reducing the period of social recovery and maintaining a high quality of life after treatment.

Introduction. Intratumor heterogeneity is one of the key reasons for unfavourable prognosis in malignant tumors. Astrocytic tumors are known to develop therapy resistance inevitably during the course of disease. One of possible reason is tumor heterogeneity. Purpose. The aim of this work was to assess the intratumor morphologic and molecular heterogeneity in diffuse astrocytoma, anaplastic astrocytomas and primary glioblastomas. Material and methods. We conducted morphologic (n=22) and molecular-genetic (n=8) analysis of surgical specimens obtained from primarily operated glioblastoma giv (gb), anaplastic astrocytomas giii (aa) and diffuse astrocytoma gii (da) patients aged 18 years and older in whom total or subtotal tumor resection was performed. Tissue sampling for the analysis was performed from 5 equidistant areas of each tumor. Morphologic diagnosis was established according to who classification of central nervous system tumors (2007/2016). Mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf genes mrnaexpression was assessed by rt-pcr. Idh1 and idh2 mutational status was evaluated by allele-specific pcr. Results. Morphologic heterogeneity was evident in 72,7 % tumors (16/22) overall. Heterogeneity was observed in 68,8 % (11/16) of gb, 80 % (4/5) of aa and in the only case of da. In 50 % of cases at least 3 different morphologic variants were seen in different areas of the tumor. This morphologic heterogeneity presented as the combination of different grades of anaplasia (gii – giv) in one tumor. Molecular profile was assessed in 48 expression analysis of genes: mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf from 8 patients. Intratumoral molecular heterogeneity was revealed in 41,7 % of cases (20/48). Conclusion. The presence of intratumoral heterogeneity should be taken into account during surgery for adequate tumor sampling for histologic and molecular analysis which is critical for proper assessment of prognosis and following treatment planning.

Due to the success of neoadjuvant systemic therapy and modern approaches to the surgical treatment of breast cancer, the proportion of organ-preserving operations has increased significantly. Radiation therapy reduces the risk of local recurrence of breast cancer after breast preservation, but entails undesirable consequences of exposure to surrounding tissues. The popularity and low frequency of side effects of accelerated partial irradiation allows us to consider it in some cases as an alternative to traditional remote irradiation in breast cancer patients.

Gastric cancer is an aggressive malignant neoplasm of the digestive system. These tumors are genetically heterogeneous,and they could be subdivided into four groups. One of such groups, microsatellite instable (MSI) gastric cancer, is of interest considering prognosis and response to therapy. Immune checkpoint inhibitors present a perspective strategy in treating these tumors, however, there is currently insufficient data on their use in microsatellite instable gastric cancer. Aim of this study was to evaluate objective response to neoadjuvant checkpoint inhibitors treatment in patients with MSI gastric cancer. Eleven patients were enrolled. They received Nivolumab or Pembrolizumab (investigator choice) in a neoadjuvant setting. Objective response was registered in 9 (81,8%) patients, two patients had stabilization. Nine patients (81,8%) underwent radical surgery. Pathologic complete response (pCR) was registered in 3 (33,3%). Postoperative complications were tracked and registered in accordance with Clavien-Dindo classification: grade 1 – 2 patients, grade 2 – 2 patients, grade 3 – 1 patient.

To date, the main way to stop dysphagia for patients with unresectable esophageal cancer is stenting. Being widely accepted and effective, this technique, however, allows for oral nutrition only for an average of 3–4 months and is accompanied by the development of a wide range of complications. Recent Russian and foreign publications in the field show that evaluation of the effectiveness of the stenting technique, including analysis of possibility of complications development, is important for practical application. To improve long-term outcomes, the potential trends in the method evolution have already been identified. The stents coated with radioactive isotopes of iodine are among of the actively used novelties. Application of 3D printing for the manufacture of custom-tailored stents, as well as the inclusion of chemotherapeutic agents in the coating of self-expanding metal stents seem promising approach. The search for a «perfect stent» continues under paradigm of personalization.

Purpose of the study. There is the generalized analysis of administration of vinflunine in real clinical practice in St.Petersburg Clinical Scientific and Practical Center of Specialized medical Care (oncological).Materials and methods. This analysis gathered 27 patients with urothelial carcinoma treated using this medicine in St.Petersburg Clinical Scientific and Practical Center of Specialized medical Care (oncological). We assessed efficacy, safety profile of vinflunine in this subset of patients.Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 51,86 %, one patient demonstrated complete response. Median of response duration accounts for 3,4 months. Adverse events were observed in 28,4 %, most of them were 1-2 grades. 2 patients stopped therapy due to adverse events.Conclusion. In our analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, confirm expediency to administer of vinflunine for metastatic urothelial carcinoma.

Purpose: To study the main risk factors of pancreatic fistula (POPF) after pancreatoduodenectomy (PD), in order to determine the degree of possible influence on them and reduce the development of early postoperative complications. Method: The results of examination and PD of 108 patients were studied from the period from 2016 to 2020. The criteria influencing the formation of POPF involved in the study: the consistency of the pancreas (determined subjectively according to the soft / hard), the diameter of the pancreatic duct, intraoperative blood loss, presence of biliary decompression (BD) before PD. Results: BD for the obstructive jaundice before PD were performed in 71 patients (65.7%), among them POPF developed in 17 patients (23.9%). In the group without BD (37 patients) in 9 (24.3 %) (p ˃ 0.05) .In patients with soft pancreas (50 patients), POPF developed in 21 patients (42.0%), among patients with hard pancreas - in 5 (5.8%) (p < 0.01). It was proposed to consider a diameter of up to 3 mm inclusively as «narrow» and «wide» from 4 or more. In 45 (41.7%) patients with a narrow duct POPF occured in 17 patients (37.8%), in 63 patients with a wide Wirsung duct (58.3%) POPF developed in 9 patients (14.3%) (p < 0.01). The volume of intraoperative blood loss less than 400 ml was regarded as physiological, this volume of blood loss was observed in 90 patients (83.3%), POPF occurred in 24 patients (26.7%), in 18 patients (17.7%) intraoperative blood loss exceeded 400 ml, POPF developed in 2 patients (11.1%) (p ˃ 0.05). All 100% of patients underwent pancreatojejunostomy at the reconstructive stage of the operation. 89 patients underwent duct-to-mucosa anastomosis, in the standard version without transanastomotic catheter, POPF occurred in 18 patients (20.0%), the rest included different options with transanastomotic catheter with or without invagination component , in this group (19 patients) PF developed in 8 people (44.4%). A statistically significant difference (p < 0.05) was obtained, however, due to the fact that a departure from the standard in the group of patients with combination of a narrow duct and soft pancreas, objectification of such a risk factor is impossible. Conclusion: In our study, the factors that significantly increase the frequency of POPF formation were the degree of pancreas density and the diameter of the pancreatic duct.

Performing immediate reconstructive plastic surgery, regardless of the type of reconstruction, reduces the level of anxiety in its various manifestations, anxiety disorders, depression, improves the quality of life and increases the level of aesthetic satisfaction of the patient with the results of surgical treatment.

OBJECTIVE of the study was to analyze the main problems and try to find the ways to improve the esophageal stenting for malignant stenosis with regard to our experience.METHODS AND MATERIALS. Palliative esophageal stenting for malignant dysphagia realized in 103 patients with observing all the patients till the fatal outcome.RESULTS. Early complications were observed in 9 patients (8.7 %) among which were: perforation of esophagus – 1 (0.97 %), minor bleeding – 2 (1.9 %), stent migration – 6 (5.8 %). Elimination of dysphagia as an immediate clinical effect was achieved in all of 103 patients (100 %) among all of early complications included. Delayed sequelae were found in 40 patients (38.8 %) among which were recurrent dysphagia because of tissue in-/overgrowth – 27 (26.2 %), stent migration – 2 (1.9 %), different kinds of esophageal fistulae – 5 (4.9 %), major bleeding – 6 (5.8 %). The most severe life-threatening complications developed at 109 days after stent placement. The mean survival rate was 131 days (from 12 till 546 days).CONCLUSION. Immediate clinical effect of stenting was achieved in 100 % of cases and delayed clinical effect was in 73.8 % of patients. Chemoradiotherapy conduces to increase the mean survival rate and, at the same time, to increase the most severe delayed life-threatening complications after esophageal stenting

The relevance of developing an intelligent automated diagnostic system (IADS) for lung cancer (LC) detection stems from the social significance of this disease and its leading position among all cancer diseases. Theoretically, the use of IADS is possible at a stage of screening as well as at a stage of adjusted diagnosis of LC. The recent approaches to training the IADS do not take into account the clinical and radiological classification as well as peculiarities of the LC clinical forms, which are used by the medical community. This defines difficulties and obstacles of using the available IADS. The authors are of the opinion that the closeness of a developed IADS to the «doctor’s logic» contributes to a better reproducibility and interpretability of the IADS usage results. Most IADS described in the literature have been developed on the basis of neural networks, which have several disadvantages that affect reproducibility when using the system. This paper proposes a composite algorithm using machine learning methods such as Deep Forest and Siamese neural network, which can be regarded as a more efficient approach for dealing with a small amount of training data and optimal from the reproducibility point of view. The open datasets used for training IADS include annotated objects which in some cases are not confirmed morphologically. The paper provides a description of the LIRA dataset developed by using the diagnostic results of St. Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology), which includes only computed tomograms of patients with the verified diagnosis. The paper considers stages of the machine learning process on the basis of the shape features, of the internal structure features as well as a new developed system of differential diagnosis of LC based on the Siamese neural networks. A new approach to the feature dimension reduction is also presented in the paper, which aims more efficient and faster learning of the system.