Objective of the study: To analyze the possibilities of the use of cytokines and of a method defi ned as cytokine gene therapy in oncology practice, based on literature data, as well as on the authors’ own experience and opinions regarding this issue.
Materials and Methods. The review includes the data from international and Russian scholarly articles found in the literature databases (e-library, PubMed) on the subject, published over the past 20 years.
Results. The feasibility and effectiveness of using cytokines in various tumors are analyzed. Particular attention is paid to the use of two cytokines in oncology practice: tumor necrosis factor and interferon-gamma. The biological mechanisms underlying these cytokines’ potential use in cancer patients, as well as the factors limiting their use in clinical practice, are described. The antitumor potential of an innovative drug, which combines two molecules—tumor necrosis factor and thymosin-alpha , as well as its combination with interferon-gamma in the comprehensive treatment of cancer patients — are analyzed. The paper outlines the defi nition and biological rationale supporting the use of cytokine-based gene therapy in oncology practice.
Conclusion. Cytokine gene therapy provides new opportunities both in the treatment and supportive care of cancer patients, thereby enhancing not only survival rates, but also, critically, overall quality of life. Further clinical trials on the antitumor effects of innovative cytokine-based drugs are needed to develop effective immunological strategies for cancer control. To devise effective immunological strategies for managing cancer, further clinical investigations into the antitumor capabilities of innovative cytokine-based drugs are indispensable.
Keywords: cancer, metastasis, cytokines, genetics, tumor necrosis factor, interferon-gamma, cytokine gene therapy
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Objective of the study: To review and enhance approaches to stratifi cation of the risk of progression and to personalization of adjuvant therapy of patients with luminal subtype A breast cancer.
Materials and Methods. The paper discusses modalities of stratifi cation of the risk of aggressiveness of luminal subtype A breast cancer, analyzes predictors of unfavorable prognosis, genetic risk factors, as well as considers and examines a clinical case of a patient with this type of cancer.
Results. The need for personalized adjuvant therapy of patients with luminal subtype A breast cancer using existing genetic panels and web calculators was proved, the use of artifi cial intelligence on the basis of a clinical case was demonstrated, the necessity of routine use of comprehensive prognostic tools to make grounded decisions on the treatment was acknowledged.
Conclusion. Considering the biological heterogeneity of this breast cancer subtype, the use of current technologies for assessing the risk of aggressiveness can greatly assist to identify patients at high risk of progression, to personalize therapy and reduce the risk of progression of this type of cancer.
Keywords: luminal subtype A breast cancer, adjuvant therapy, genetic panels, composite indices, clinical statistical models
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Objective of the study: To determine the role of FOXL2 gene in the clinical course and prognosis in patients with granulosa cell tumors of the ovaries.
Materials and Methods. The study comprised the patients with histologically verifi ed diagnosis of granulosa cell tumor, who had undergone treatment at N. N. Blokhin National Medical Research Center of Oncology for the period from 2015 to 2020. Histological samples were obtained from 36 patients. The presence of p.C134W mutation in FOXL2 gene was assessed using direct sequencing method (ABI 3500 Genetic Analyzer). In 6 cases, due to a severe level of DNA fragmentation, a satisfactory result could not be obtained, and therefore the data was not included in the analysis. Thus, 30 cases were further analyzed. The study included the following stages: 1. DNA extraction from tumor cytology material. 2. Carrying out polymerase chain reaction (PCR). 3. Performing direct sequencing using Sanger sequencing method.
Results of the study. It was established that p.C134W mutation in FOXL2 gene is signifi cantly less common in granulosa cell tumors (GCTs) at early (I A, B) and “conditionally early” (IC) stages of the disease. Conversely, relapses were observed more frequently in the presence of the mutations and at more advanced stages of the process: in 75 % of cases versus 50 % of observations without mutations, which in conjunction with tumor necrobiosis, worsened the prognosis.
Conclusion. The obtained results allow to conclude, that p.C134W mutation in FOXL2 gene in granulosa cell tumors contributes signifi cantly to the course of the disease and its prognosis.
Keywords: granulosa cell tumor of the ovaries (GCT), FOXL2, TERT, TP53, KMT2D, AKT1, SIRT1, RUNX1, molecular markers
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Introduction. Treatment of recurrent endometrial cancer (EC) is a compelling clinical issue in gynecologic oncology. The choice of optimal treatment for such patients depends on the localization of recurrent tumor, its volume, as well as on the nature of previous treatment and a patient’s functional status. Indications for surgical intervention for recurrent endometrial cancer are not distinctly specified.
Objective of the study: To analyze clinical and morphological characteristics and outcomes of the treatment of patients with isolated recurrence of endometrial cancer (EC) who underwent surgical intervention.
Materials and Methods. Medical records of 35 patients with isolated recurrence of endometrial cancer of various localizations, who had undergone surgical intervention at Department of Gynecologic Oncology at N. N. Blokhin National Medical Research Center of Oncology for the period from 2018 to 2023 were analyzed retrospectively. All patients were divided into three groups based on the type of recurrence: lymphogenous — 18 (51 %), local — 7 (20 %), peritoneal — 10 (29 %).
Results. The median overall survival was 63 months. The 3-year and 5-year overall survival (OS) rates in the entire group of patients with local recurrence of endometrial cancer (EC) were 80 % and 75 %. The assessment of long-term outcomes of surgical treatment of patients based on the type of recurrence revealed that 3-year survival in the group of lymphogenous tumor spread was 77 %, in the cohort of local recurrence — 67 %, and in the group of peritoneal spread — 90 % (p > 0,05). Patients with lymphogenous recurrence of endometrial cancer (EC) were analyzed separately on the basis of the localization of the affected lymph nodes: the rate of 3-year overall survival (OS) in patients with metastatic lesion of para-aortic lymph nodes made up 41 %, pelvic lymph nodes — 100 %, pelvic and para-aortic — 100 %, and in the presence of distant metastases manifested as the lesion of inguinal lymph nodes — 80 % (p = 0,472).
Conclusions. Surgical intervention, when incorporated into a comprehensive treatment plan, should be considered for carefully selected patients with isolated recurrent endometrial cancer (EC), including those with lymphogenous spread, as it signifi cantly enhances patient survival. More research is required to establish clear guidelines on the surgical treatment of recurrent endometrial cancer (EC).
Keywords: endometrial cancer, type of recurrence, isolated recurrence, lymphatic recurrence, surgical treatment, cytoreductive operation
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Cotyledonoid dissecting leiomyoma (CDL) — is a rare benign neoplasm of the uterus which was fi rst described by Dr. William Sternberg in 1979. This article presents a clinical case of cotyledonoid dissecting leiomyoma (CDL) in a 48-year-old patient, delineates the clinical manifestations, macro- and microscopic features of this tumor. Particular attention is given to differential diagnosis with benign smooth muscle cell tumors, low-grade endometrial stromal sarcoma and leiomyosarcoma. The article emphasizes the signifi cance of morphological verifi cation of this neoplasm, aiming at the selection of organ-sparing surgical strategy and preservation of the patients’ reproductive potential.
Keywords: dissecting growth, benign tumor of the uterus, surgical treatment
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Objective of the study — is to evaluate the effectiveness of aromatase inhibitor letrozole in the programs of primary and secondary preservation of genetic material (oocytes and embryos) with due consideration of the state of ovarian reserve in women with breast cancer.
Materials and Methods. Thirty fi ve women with breast cancer underwent primary (17 patients) and secondary (18 patients) oocytes/embryos retrieval and deposition programs in stimulated cycles using letrozole. The relationship between the obtained results and the state of ovarian reserve, indicated by AMH levels (< or ≥ 1 ng/ml), was verified.
Results. In the programs of primary and secondary fertility preservation in women with breast cancer and normal AMH levels, the use of letrozole in the stimulated cycles provided the possibility of depositing genetic material in the absolute majority (from 2/3 to 3/4) of patients, although the number of oocytes retrieved in each successfully completed cycle did not exceed 2-3, and embryos — 1-2.
Conclusions. The use of letrozole for ovarian stimulation in the programs of primary and secondary preservation of reproductive potential in women with breast cancer permits to perform oocyte/embryo retrieval in the majority of individuals with normal state of ovarian reserve. It appears feasible to use letrozole in patients with breast cancer primarily in the programs of secondary preservation of genetic material, which allow for multiple stimulation with this drug to increase the supply of obtained oocytes/embryos.
Keywords: infertility, breast cancer (BC), letrozole, cryopreservation of oocytes and embryos
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Cancer patients are at high risk of developing both venous and arterial thrombosis. This link was fi rst described by Trousseau who made a signifi cant clinical discovery, fi nding that an occurrence of thrombus migration in some cases precedes the detection of malignant neoplasms. Pathogenesis of thrombosis in patients with malignant diseases is complex and multifactorial. The mechanisms of thrombus formation can be enhanced by anti-tumor drugs and radiation therapy. Ananalysis of the world academic literature suggests that arterial and venous complications share common risk factors and often occur in the same patient. While the relationship between malignant neoplasms and venous thrombosis has been well studied, arterial thromboses are described to a lesser extent due to their relatively rare occurrence. Fewer than 50 cases of spontaneous arterial thrombosis without iatrogenic cause and which occurred not due to atherosclerotic factors in cancer patients, have been reported in the literature. Arterial thromboembolism has a substantial negative impact on both morbidity and mortality. Currently, both conservative and surgical methods of treatment are used for this severe complication. This article presents the main stages of diagnosis and treatment of a patient with ovarian granulosa cell tumor and thrombosis of infrarenal segment of the aorta extending to the right common iliac artery with the development of distal multilevel embolism of deep femoral, popliteal artery and right tibial arteries, based on a real clinical case.
Conclusion. Thrombosis of the infrarenal segment of the aorta extending to the right common iliac artery with the development of distal multilevel embolism of deep femoral, popliteal artery and tibial arteries — is a rare complication among all malignant neoplasms of female reproductive organs, that require complex surgical interventions, operating room first-rate technical equipment and facilities, multidisciplinary cooperation, that can be provided only at profoundly expert comprehensive wide-ranging medical institutions, offering diverse and highly specialized services.
Keywords: venous thrombosis, arterial thrombosis, oncological diseases
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Objective of the study — is to assess the state of reproductive and menstrual cycle function of patients, who underwent ovarian transposition before radiation therapy for rectal and anal cancer , as well as to examine the condition of their uteri, with due regard for the previous radiation therapy for the pelvis.
Materials and Methods. The study included 23 patients aged from 27 to 48 years diagnosed with rectal and anal cancer. All patients underwent ovarian transposition before radiation therapy. The patients received primary antitumor treatment at Department of Colorectal Surgery of N. N. Blokhin National Medical Research Center of Oncology for the period from 2022 to 2024.
Results. Among 22 patients who had had regular menstrual cycles before cancer treatment, menstrual function was restored after radiation therapy only in 2 patients, which made up 9 % rate compared to 91 % of cases of complete disruption of menstrual cycle after the treatment. The results of the analysis of ovarian reserve confi rmed commonly recognized and accepted patterns, predicting a sharp decline in ovarian reserve and ovarian insuffi ciency in patients after chemotherapy and radiation therapy.
Conclusions. It is essential to preserve genetic material prior to the treatment or to enhance ovarian transposition technique, especially for the groups of women of young age, who didn’t manage to fulfi l their reproductive desires and potential or who wish to conceive again.
Keywords: oncofertility, infertility, rectal and anal cancer, oocyte and embryo cryopreservation
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