Background. Breast cancer is the most common cancer in women. The main treatment for breast cancer includes surgery, chemotherapy, radiation therapy, and hormone therapy. The role of radiation therapy in the management of breast cancer continues to evolve. Radiation therapy is currently being de-escalated to include the use of intraoperative radiotherapy (IORT) and adjuvant endocrine therapy. Purpose of the study: to compare the efficacy of IORT with that of external beam radiotherapy (EBRT) in the treatment of early breast cancer. Material and Methods. A retrospective study of 559 patients with early breast cancer was conducted in Clinical Oncology Center of Saint Petersburg. The main treatment group included 273 patients who underwent breast-conserving surgery with IORT and sentinel lymph node biopsy. The control group included 286 patients who underwent breast-conserving surgery with sentinel lymph node biopsy and EBRT. Results. For all patients, the median follow-up time was 59.1 months (interquartile range: 43.7 to 80.7), the minimum follow-up period was 0.6 months, and the maximum follow-up period was 110.4 months. Recurrence occurred in 18 (6.6 %) patients of the main group and in 8 (2.8 %) patients of the control group. A statistically significant association of biological subtype with survival outcomes was found (p=0.02). The hazard ratio for Luminal B of 1.88 (95 % CI 1.02, 3.46) corresponded to a 65 % chance of an earlier onset of a negative outcome. The hazard ratio for triple-negative breast cancer of 3.01 (95 % CI 1.53, 5.95) corresponded to a 75 % chance of an earlier negative outcome. In the main treatment group, 11 (4 %) patients developed disease progression, and 2 of them died of multiple organ failure. In the control group, disease progression was observed in 18 (6.3 %) patients, 6 of whom died. However, the analysis of overall survival using the Kaplan–Meier curve showed a statistically non-significant log-rank p-value (0.73). The 3-year survival rates were 100 % (100 – 100) in the treatment group and 98.2 % (96.7 – 99.8) in the control group. The 5-yaer survival rates were 99.3 % (97.9 – 100) in the treatment group and 97.8 % (96.2 – 99.6) in the control group. These results showed advantage of IORT over EBRT. Conclusions. Intraoperative radiotherapy is a safe and effective alternative to external beam radiotherapy for early breast cancer.

The aim of the study was to analyze of the safety and feasibility of neoadjuvant chemotherapy (2 cycles of FLOT chemotherapy + chemoradiotherapy) followed by surgery in the treatment of locally advanced gastric cancer. Material and Methods. The phase II clinical trial included 47 patients with histologically verified locally advanced gastric cancer (cT3/T4a-b: 26/21 and cN0/N1–3: 20/27) treated at the A.F. Tsyba MRRC from 2018 to 2021. Lesion location was: upper third in 19 patients (esophageal invasion in 9 patients), middle third in 13 patients, lower third in 14 patients, and entire stomach in 1 patient. The tumor grade was G3 in 23 patients, G2 in 13 patients and G1 in 7 patients. Signet ring cell carcinoma was revealed in 4 patients. The patients received 2 cycles of induction chemotherapy with FLOT regimen (85 mg/m² oxaliplatin + 200 mg/m² calcium folinate + 50 mg/m² docetaxel on day 1 + 2600 mg/m² fluorouracil as 24-hour infusion from day 1; every 2 weeks) followed by 3d-conformal external beam radiotherapy (46 Gy in daily fractions of 2 Gy) combined with chemotherapy with capecitabine and oxaliplatin). The patients then underwent follow-up examination to exclude disease progression and to plan surgery. Postoperative complications were analyzed using the Clavien-dindo classification. Results. Induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated. Forty-five (95.7 %) patients underwent surgery, 97.7 % of them underwent radical surgery. Postoperative complications were observed in 11 (23.4 %) patients. Grade III and more severe complications were observed in 3 (6.4 %) patients. It should be noted that postoperative mortality rate was low, amounting to 2.2 % (1 patient). Conclusion. Induction FLOT polychemotherapy followed by concurrent chemoradiotherapy was shown to be safe, feasible, and tolerable. Moreover, this treatment regimen did not reduce the frequency of R0 surgeries and did not increase incidence and severity of postoperative complications.

Cytoreductive nephrectomy (CN) and metastasectomy are justified in patients with oligometastatic renal cell carcinoma (RCC). Objective: to evaluate the impact of cytoreductive surgery on survival rates in patients with oligometastatic RCС. Material and Methods. We retrospectively analyzed the data of 342 patients with oligometastatic RCC, who underwent systemic therapy and different types of cytoreductive surgeries at the Municipal Oncology Hospital No. 62 in Moscow and the Municipal Oncoloy Center in Saint Petersburg from 2006 to 2022. Cytoreductive nephrectomy was performed in 332 (97.1 %) patients, metastasectomy in 103 (30.1 %) patients. The survival rates of patients in treatment groups were evaluated using the Survival Analysis by calculating descriptive characteristics of survival time by means of a life-table and Kaplan–Meier curves. The results were considered statistically significant at p<0.05. Results. In the univariate analysis, in patients who underwent CN, the factors that had a negative effect on the prognosis of survival rates were the tumor grade, evidence of bone metastases, levels of ALP, LdH, ESR, as well as prognosis according to the IMdC model and metastasectomy. In the multivariate analysis, only IMdC prognosis was found to have a negative effect on survival rates. In both the univariate and multivariate analysis, in the group of patients who underwent metastasectomy, IMdC prognosis alone had an unfavorable impact on survival rates of patients with oligometastatic RCC. Conclusion. Our study showed that CN and metastasectomy had a statistically significant effect on OS (p=0.02 and p=0.032) of patients with oligometastatic RCC. division of the patients into prognosis groups according to the IMdC model showed that CN did not improve the OS rates in patients with oligometastatic RCC with intermediate and unfavorable prognosis, and metastasectomy significantly increased the OS rates in oligometastatic RCC patients with favorable and unfavorable prognosis (p=0.0055 and p=0.047). When evaluating prognostic factors in patients undergoing CN and metastasectomy, only IMdC prognosis had an impact on the OS rates (p<0.001).

Introduction. Testicular cancer (TC) mostly affect young men of reproductive age. Several studies have shown correlation between the level of sex hormones in testicular cancer and serum tumor markers. However, currently, the relationship between hormone levels before orchidectomy and the clinical and pathomorphological characteristics of the tumor has not been sufficiently studied. Aim of the study: to analyze the relationship between hormone levels and the clinical stage and histological characteristics of the tumor in patients with testicular cancer and to develop prognostic models. Material and Methods. This prospective single-center study included 66 patients with testicular cancer. Localized, locally advanced and metastatic testicular cancer was diagnosed in 55 (83.3 %), 9 (13.6 %) and 2 (3.0 %) patients, respectively. A preoperative assessment of hormones such as total and free testosterone (T), estradiol (E2)), gonadotropic hormones (LH, FLH, Prolactin) and b-HCG was carried out. Patients were divided into 2 groups depending on the histological structure of the tumor: seminoma (n=31) and non-seminoma (n=35). The following parameters were assessed: tumor size, lymphovascular invasion and rete testis invasion. Results. In non-seminoma tumors, the values of sex hormones and beta-hCG were higher, but the values of gonadotropic hormones were lower compared with typical seminomas (p<0.05). High concentrations of b-HCG were observed predominantly in pT3 compared to pT1 stages (p=0.018). Correlation analysis revealed a connection between total (ρ=0.351; p=0.004) and free T (ρ=0.342; p=0.008), E2 (ρ=0.292; p=0.022), b-HCG (ρ=0.244; p= 0.048), LH (ρ=-0.287; p=0.039), FSH (ρ=-0.264; p=0.04) and the size of the primary tumor. The presence of rete testis invasion was accompanied by a low LH value and a high b-HCG value compared to patients without this prognostic parameter (p=0.015, p<0.001, respectively). Prognostic models were developed to determine the probability of histological structure and the presence of rete testis invasion (p<0.001) with high sensitivity (82.1 % and 76.5 %) and specificity (76.9 % and 100 %). Conclusion. The findings suggest that non-seminoma tumors are associated with changes in the pituitary-gonadal (HPG) axis. The high values of sex hormones and low values of gonadotropic hormones before orchidectomy are associated with a large size of the primary tumor. Additionally, a low LH value and a high b-HCG value are predictors of rete testis invasion. High b-HCG levels are associated with more aggressive tumor biology and poor prognosis.

Introduction. Chronic lymphocytic leukemia (CLL) is a disease characterized by large individual differences both in the clinical course and in molecular patterns of expression of genes and regulatory RNAs, which can influence pathological changes. The involvement of regulatory microRNAs miR-155 and miR-223 in the pathogenesis of CLL is fairly well known, but there is insufficient information about possible fluctuations in the expression of miR-155 and miR-223 depending on the time course of pathology development and on parameters of medical treatment. Purpose – to investigate the expression of miR-155 and miR-223 in patients having CLL with different biological and clinical features and different characteristics of treatment in terms of peripheral-blood substrates (plasma, lymphocytes, and extracellular vesicles) and bone marrow. Material and Methods. This work involved samples of peripheral blood and bone marrow from 38 patients with a diagnosis of CLL from the City Hematology Center at the government-funded healthcare institution (Novosibirsk Oblast) City Clinical Hospital No. 2 from the years 2016 to 2017. Assessment of miR-155 and miR-223 expressions was carried out by reverse-transcription real-time PCR according to the TaqMan principle. Significance of differences between groups was evaluated either by the nonparametric Mann–Whitney test or by the nonparametric Kruskal–Wallis test with subsequent pairwise comparisons via the Mann–Whitney test. Results. High variation of the analyzed parameters was found. The expression levels of miR-155 and miR-223 in microvesicles of patients with unfavorable chromosomal anomalies were lower than those in patients with the chromosomal aberrations (or the normal karyotype) associated with a moderate effect on CLL prognosis. The expression level of miR-223 in peripheral blood lymphocytes of untreated patients with CLL was higher than that observed in treated patients. Conclusion. differences in the expression levels of miR-155 and miR-223 were identified depending on chromosomal aberrations and polychemotherapy. Our preliminary results will provide the basis for future larger studies on levels of microRNAs in CLL patients having specific features of the development, clinical course, and treatment of the disease.

Functioning of the PD-1/PD-L1 immune checkpoint in the microenvironment of breast cancer may lead to the tumor escape from the immune response. However, it is unknown how often PD-L1 binds to PD-1 in breast cancer patients, which PD-L1-positive cells are predominantly involved in the interaction, and what prognostic significance it has. The objective of the study was to assess the frequency of co-location of PD-1/PD-L1- positive cells in the microenvironment of breast cancer as well as to determine the population of these cells. Material and Methods. The study included 25 patients with invasive breast carcinoma. Interaction between cells carrying the PD-1 receptor and the PD-L1 ligand in the tumor microenvironment were visualized using multiplex TSA (tyramide signal amplification)-modified immunohistochemistry. Participation of M1 macrophages (CD68+CD163-CD3-CKAE1/3-), M2 macrophages (CD68+/-CD163+CD3-CKAE1/3-), lymphocytes (CD68- CD163-CD3+CKAE1/3-) and other immune cells in these interactions was assessed. Results. Half of the breast cancer patients included in the study had interactions of immune cells of the microenvironment, one of which carried PD-1, and the other carried PD-L1. The contact of cells carrying PD-1 and PD-L1 was associated with the level of TILs and the ratio of PD-1+/ PD-L1+ cells in the tumor microenvironment. The PD-1/PD-L1 interaction was found with similar frequency in PD-L1 positive and negative patients. In the cell contacts, macrophages acted as PD-L1+ cells in the vast majority of cases. Lymphocytes were PD-1-positive cells rather than PD-L1- carrying cells. In addition, it was found that metastasis-free survival was not associated with the presence or absence of co-localized cells carrying PD-1 and PD-L1 in the tumor microenvironment. Conclusion. Co-location of immune cells carrying PD-1 and PD-L1 occurs in breast cancer. M1 and M2 macrophages, CD3+ lymphocytes and other immune cells are involved in these interactions. However, further studies are needed to establish the prognostic significance of these contacts.

The purpose of the study was to evaluate the efficacy of neutron therapy (NT) for salivary gland cancer and recurrent breast cancer. Material and Methods. The study included 130 patients with salivary gland cancer and 125 patients with recurrent breast cancer. Fast neutron therapy using U-120 cyclotron was given to the patients of the study group. Patients of the control group received standard radiotherapy (external beam radiotherapy). Results. Among patients with salivary gland cancer, a recurrence rate was significantly lower in patients who received a postoperative course of NT compared to patients of the control group (21.1 vs 45 %, p<0.05). The five-year overall survival rates were 73.8 ± 9.5 % and 43.2 ± 9.4 % in the study group and the control group, respectively (p<0.05). The five-year disease-free survival rates were 65.6 ± 7.5 % and 34.8 ± 9.1 % in the study and control groups, respectively (p<0.05). In patients with recurrent breast cancer, a significant increase in the frequency of complete regression in the study group compared to the control group was observed (91.8 vs 51.3 %, p<0.05). Ten-year survival rates in patients with no evidence of re-recurrence were 77.4 ± 8.7 % and 44.7 ± 8.8 % in the study group and the control group, respectively (p<0.05). Conclusion. The study demonstrated efficacy of fast neutron therapy in patients with salivary gland cancer and recurrent breast cancer. Neutron therapy did not result in serious complications, improved survival of the patients and decreased the recurrence rate compared with standard radiotherapy.

Purpose of the study: analysis of our experience in performing robotic-assisted nephron-sparing surgeries using the da robotic system. Material and Methods. The retrospective study included the first 37 consecutive patients who underwent robot-assisted partial nephrectomy from May 2020 to december 2022. Results. To assess the surgical outcomes in patients undergoing partial nephrectomy, three parameters associated with trifecta achievement were analyzed. The trifecta was assessed according to the standard criteria, whereas the quadfecta, which in addition to the trifecta included preservation of >90 % of the glomerular filtration rate (calculated according to Cockroft–Gault) in the postoperative period (3–7 days), did not assess the stage of chronic renal failure one year after surgery, thus probably demonstrating the high percentage of its achievement (54.1 %). A positive surgical margin was observed in 1 (2.7 %) patients. Warm ischemia time of more than 25 minutes was used in 8 patients (21.6 %). Complications in the postoperative period (Clavien–Dindo II and higher) were observed in 1 (2.7 %) patient. Trifecta and quadfecta rates were 78.4 % and 54.1 %, respectively. To analyze the surgeons’ experience, 37 renal cell cancer patients were divided into two subgroups with first 20 and subsequent robotic partial nephrectomies. There were no differences in gender, age and calculated RENAL value between 2 subgroups. depending on the surgeons’ experience, statistically significant differences in the duration of surgery (p=0.035) and blood loss during surgery (p=0.007) were found. Conclusion. Considering the extensive experience of surgeons in the field of laparoscopic surgery for tumors of the renal parenchyma, the outcomes of robotic partial nephrectomies performed in 37 patients seem to be satisfactory and successful. The accumulated experience of surgeons after 20 robotic-assisted nephron-sparing surgeries makes it possible to significantly reduce surgery time and blood loss. The technique of robotic-assisted partial nephrectomy requires further improvements.

The abscopal effect in oncology has been known for 70 years, but until recently its clinical significance was rather low. The development of immune response checkpoint inhibitors has led to an active study of this phenomenon. There is now evidence of improved survival among patients, in whom the abscopal effect has been documented, opening new perspectives for the treatment of cancers at different stages. This review presents data on the mechanisms of the abscopal effect, experimental and clinical data, current limitations and possible perspectives. The aim of the study was to investigate the current concept of the abscopal effect occurrence and to evaluate the prospects of using the abscopal effect in therapy of metastatic cancer. Material and Methods. We searched publications in Pubmed system from 2010 to 2023. Of 286 publications, 72 were used for writing the review. Results. In the era of widespread use of immune checkpoint inhibitors (ICIs) for cancer therapy, the abscopal effect appears to be an effective therapeutic approach with broad prospects of application in the treatment of patients with metastatic cancer. Conclusion. The incidence of the abscopal effect has increased with the advent of immune therapy, and the use of ICIs with radiation therapy (RT) has shown improved survival even in patients with advanced disease. More research is needed to establish standardized treatment protocols, including the optimal dose and timing of RT, as well as the efficacy and safety of combination therapy with different classes of ICIs. Further search for clinical and laboratory abscopal effect predictors, which could allow personalized treatment approaches, is required.

The aim of the study was to assess the frequency and clinical significance of various molecular genetic aberrations in biliary tract tumors and to determine the optimal methods of their testing. Material and Methods. We searched the literature sources containing information on predictive molecular markers relevant for the choice of therapy in biliary tract tumors in PubMed and eLibrary databases for the period from 2010 to 2023. data from 60 studies were included in this review. Results. Biliary tract tumors are characterized by poor prognosis and low sensitivity to major systemic therapies. Nevertheless, the emergence of new targeting drugs and prescription of therapy based on the results of molecular genetic analysis can increase the life expectancy and improve the quality of life of a significant proportion of patients. The most frequently detected clinically significant abnormalities in all biliary tract tumors include HER2 gene amplification/hyperexpression (5–20 % of cases), microsatellite instability (1–2 % of cases), BRAF V600E oncogene mutation (1–2 % of cases) and KRAS G12C oncogene mutation (about 1 % of cases). Specific targetable abnormalities unique to intrahepatic cholangiocarcinomas include aberrations in the gene encoding fibroblast growth factor receptor 2, FGFR2 (10–20 % of cases) and mutations in the gene encoding the enzyme isocitrate dehydrogenase 1, IDH1 (5–30 % of cases). Very rare clinically significant molecular markers for biliary tract tumors include translocations involving the receptor tyrosine kinase genes NTRK1-3, RET, ALK and ROS1. Mutations in the genes of the dNA double-strand break repair system by the mechanism of homologous recombination are also potentially significant for the choice of therapy. First of all, these are BRCA1/2 genes, hereditary mutations in which, according to two studies, are characteristic of 5–7 % of patients with biliary cancer. Although a significant part of the above-mentioned disorders can be detected by traditional molecular biological approaches such as PCR, IHC, FISH and Sanger sequencing, a comprehensive analysis of all molecular markers of predictive value in biliary tract tumors is difficult to perform without the help of next-generation sequencing (NGS). Conclusion. To improve treatment outcomes of patients with advanced and metastatic biliary tract cancer by individualizing drug therapy, it is necessary to perform comprehensive molecular genetic analysis of tumour tissue.

Background. Glioblastoma (GB) remains an aggressive disease with a poor prognosis. despite a comprehensive approach to the treatment of the primary disease, recurrence is almost inevitable. There is still no standard of care for GB recurrence, and many guidelines recommend treating these patients within clinical trials. There are various treatment options available. They include surgery, radiation therapy, systemic or regional chemotherapy or targeted therapy, various immunotherapy strategies, low- and medium-frequency electric fields, and their combinations. The combination of two non-invasive techniques: re-irradiation and systemic targeted therapy remains the most commonly used approach in this group of patients, the potential of which has not been fully realized. The aim of the study was to analyze the literature data on the use of the combination of re-irradiation with bevacizumab as a therapeutic option in patients with GB. Material and Methods. Literature search was performed using Medline, Cochrane Library, E-library, Scopus, PubMed and Google Scholar databases. Results. The current state of the problem was determined, the data available to date on the use of repeated radiotherapy with competitive and/or adjuvant bevacizumab in the treatment of GB recurrence were summarized and analyzed, different regimens of this approach were compared, and the prospects and possible ways of solving the existing problems of this therapeutic option were described. Conclusion. Re-irradiation with concomitant administration of bevacizumab may provide safer treatment of GB recurrence, including large-volume glioblastoma, with acceptable toxicity, in particular radiation necrosis, especially when an appropriate fractionation schedule is used.

Background. The incidence of liver malignancies is increasing, radical surgery can be performed in a small number of patients, most of them receive drug treatment. Isolated liver chemoperfusion (ILP) is a method of regional chemotherapy that is effective for some metastases but has a high complexity and frequency of complications. An improved method of hybrid ILP may offer new opportunities for patients with unresectable liver tumors. Case report. A 64-year-old patient diagnosed with stage IV sigmoid colon cancer underwent hybrid ILP. The patient was discharged after 6 days in a satisfactory condition without complications. Systemic chemotherapy was performed 21 days after the first hybrid chemoperfusion. The second hybrid chemoperfusion procedure was performed without the laparotomy stage, mobilizing the right common femoral vein and artery. As a result of the chemotherapy, the patients received a positive result on the mRECIST scale – a complete tumor response. Conclusion. The developed method of hybrid ILP has several advantages over traditional ILP and chemosaturation with infusion into the hepatic artery. This method can also be performed repeatedly, which is not possible with traditional ILP.

Background. Colorectal cancer is one of the most common cancers and the second leading cause of cancer-related deaths worldwide. Population-based studies have shown that 25–30 % of patients with colorectal cancer have synchronous liver metastases at the time of diagnosis. despite modern advances in oncology and surgery, only 25 % of patients with metastatic colorectal cancer (mCRC) are suitable for liver resection, which is the only curative treatment option for these patients. In recent years, the indications for curative treatment of mCRC have expanded. due to the introduction of new targeted drugs into clinical practice, the tumor response rate to preoperative therapy has increased, thus increasing surgical resection rate. Some patients experience a complete clinical response, which is defined as the complete disappearance of liver metastases. However, 30–70 % of patients develop recurrent metastases in the liver within the first year of follow-up, and currently, even in the presence of complete regression of metastases, it is recommended to perform resection of the initially affected hepatic segments. Case presentation. We describe a case of complete clinical and radiological response of liver metastases after chemotherapy in a patient with sigmoid colon cancer. Molecular genetic analysis revealed the wild type of the Kras, Nras and Braf genes. The patient received 3 courses of preoperative chemotherapy according to the FOLFOxIRI + Cetuximab regimen. Laparoscopic sigmoid colon resection with d3 lymph node dissection was followed by adjuvant chemotherapy with oxaliplatin and 5-fluorouracil (12 cycles). After 16 months of follow-up, no evidence of colon cancer recurrence and liver metastasis was found. Conclusion. Current targeted therapy has demonstrated efficacy in treating mCRC with synchronous liver metastases and makes it possible, in selected cases, to avoid the liver resection provided that a complete clinical and radiological response of the metastases is achieved.

Background. Overexpression of Her2neu occurs in 15–20% of patients with gastric cancer and correlates with an unfavorable prognosis. Case report. We report a case of pathological complete regression of resectable gastric cancer with Her2/neu overexpression. The patient received combined modality treatment including 8 cycles of neoadjuvant chemotherapy with mFLOT + trastuzumab followed by R0 resection. The addition of targeted therapy did not have a negative impact on the perioperative period. Histolohical examination of the surgical specimen revealed pathological complete response (Mandart TGR1). Currently, the patient has been followed-up for 27 months without signs of disease relapse. Conclusion. Total neoadjuvant chemotherapy with mFLОТ+ trastuzumab for operable gastric cancer with Her2/neu overexpression allows us to hope for improved long-term treatment outcomes.