OBJECTIVE:Breast cancer is a public health problem with increasing incidence, prevalence, and mortality worldwide. Germline variants in the DNA repair genes BRCA1/2 are involved in the pathogenesis of hereditary breast/ovarian cancer. However, for many ethnic groups that are isolated geographically worldwide, founder variants of breast cancer still have not been found. In this study, we provide whole exome sequencing data performed in a group of breast/ovarian cancer patients who belong to the Buryats. METHODS:Our study included 56 Buryat patients with histologically confirmed primary breast/ovarian cancer who completed an anonymous questionnaire about basic information and nationality. Genomic DNA was isolated from peripheral blood leukocytes. Libraries were prepared using a BGI Optimal DNA Library Prep kit (MGI, China). An Agilent SureSelect Human All Exon V6 kit (Agilent, USA) was used for hybridization. High-throughput sequencing was performed on a DNA nanoball sequencing platform DNBSeq-G400 (MGI, China).  Result: In the overall group of patients with signs of hereditary breast/ovarian cancer, likely pathogenic/pathogenic variants were detected in 16% (9/56). We have discovered likely pathogenic/pathogenic variants that can either directly (BRCA2, RAD51D, FANCG) or indirectly (POLR2C, FOXL2, GDF9, CYP21A4) initiate breast/ovarian cancer. For the first time, three rare germinal variants in the BRCA2 gene were detected in a small Buryat ethnic group. Further studies are required to confirm their role in the pathogenesis of breast /ovarian cancer in this ethnic group. We found that the RAD51D gene variant c.757C>T is recurrent and was observed in 4% of Buryat patients with breast/ovarian cancer. CONCLUSION:For the first time, rare germinal variants in the BRCA2, RAD51D, FANGC, CYP24A1 genes were detected in a small Buryat ethnic group. Our data are consistent with existing data showing that variants in the RAD51D gene may be involved in the pathogenesis of breast/ovarian cancer. We also showed that the Mongolic-speaking Buryat populations exhibited strong genetic resemblance to those of Chinese.

Introduction:The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) may be considered an effective option in the neoadjuvant setting for metastatic colon cancer (mCRC). To investigate potential molecular criteria for treatment response, we evaluate the transcriptome of paired primary colon tumors and liver metastases. Method:Two sets of quadruple-matched specimens (primary colon tumor, liver metastasis, normal colon and liver tissues) from five patients with resectable mCRC before and after neoadjuvant FOLFOXIRI were selected for RNA sequencing (RNA-seq). Results:RNA-seq data showed that liver metastases exhibited a higher number of differentially expressed genes (DEGs) than colon tumors (FDR < 0.05, 301 vs. 62, respectively). Up-regulation of IL1RN, MTCO1P12, RN7SL1, ALDH1A1, DUSP1, COX1, and FOS may be associated with colon tumor sensitivity to FOLFOXIRI. HBB, GADD45B, DUSP1, FOSB, HBA2, TSC22D3, TAGLN, PER1, CSRP1, CCN2, NAMPT, ZBTB16, SERPINE1, ISG20, SRGN, ATF3, IL7R, IFITM2, and KLF2 may potentially be involved in the partial liver metastasis response. EPS8L2 was the only gene highly expressed in pre-treatment liver tissue of the complete responder patient compared to others (|Log2FC| = 3.84, FDR < 0.05). Conclusion:Data obtained indicate transcriptional discordance between the primary tumors and liver metastases during neoadjuvant FOLFOXIRI, with the pattern of DEGs involved in their response being distinct. The EPS8L2 transcript could be regarded as a candidate biomarker of liver complete response; however, prognostic conclusions cannot be drawn from this cohort.

Hereditary breast cancer is an autosomal dominant disease caused by variants in genes such as BRCA1/2, RAD51, ATM, BRIP1, and others. In a previous study using whole exome sequencing, we identified a germline variant of the LGR4 gene (rs34804482, NM_018490.5(LGR4):c.2531 A > G (p.Asp844Gly)) in a young Tuvan breast cancer patient (belonging to the Turkic-speaking tribes of Central Asia). The aim of this study was to determine the frequency of the variant of the LGR4 gene NM_018490.5(LGR4):c.2531 A > G (p.Asp844Gly) in ethnic groups of West Siberia using the PCR-RT method. The study involved 735 breast cancer patients from ethnic groups in Siberia, median age at diagnosis of 43 ± 15.6 years. The control group consisted of 727 healthy women from Siberia, median age of 43.05 ± 13.5 years. The frequency of this variant (rs34804482) was 0.015 in Russian, 0.022 in Buryat, and 0.069 in Tuvan breast cancer patients. In Tuvan women with breast cancer, the frequency of the LGR4 gene variant was significantly higher than in Russian BC patients (0.069 versus 0.015, X2 = 8.153, p = 0.005). The frequency of the LGR4 gene variant (rs34804482) in healthy Tuvan women was significantly higher than in healthy Russian women (0.066 versus 0.016, X2 = 6.368, p = 0.012). The variant frequency in healthy Russians was close to that in Europeans (0.016 versus 0.0219). We found no statistically significant differences in the rs34804482 frequency between breast cancer patients and healthy individuals in the ethnic groups studied. The highest frequency of this missense germline variant was observed among Tuvans.

AIM: assess the impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period.PATIENTS AND METHODS: a pilot prospective study included 30 patients with colorectal cancer and synchronous liver metastases (mCRC). The combined treatment included 3 cycles of neoadjuvant FOLFOXIRI chemotherapy with the addition of targeted agents: cetuximab (24 patients with wtKRAS) and bevacizumab (6 patients with mtKRAS) followed by radical surgery.RESULTS: the clinical and radiological response of colorectal cancer liver metastases to neoadjuvant chemotherapy (NACT) was complete in 4 (13.3%) patients and partial in 26 (86.7%) patients. Partial response to NACT in the primary tumor occurred in all patients. Adverse events of NACT were detected in 12 (40%) patients, 1 (3.3%) of them produced grade III toxicity. All patients underwent radical surgery (R0) 3–4 weeks after NACT, 28 (93.3%) of them underwent simultaneous colorectal and liver resection. Postoperative complications occurred in 21 (70%) patients, including grade I and grade IIIa complications (according to Сlavien-Dindo classification) — 22 (73.3%) and 2 (6.7%), respectively. Histology revealed pathologic complete response (pCR) of liver metastases in 1 (3.6%) case and pathological grade 3 regression of the primary tumor (TRG3, Mandard A.M.) in 23 (76.7%) patients. Two (6.7%) patients with complete clinical and radiological response of liver metastases, who did not undergo liver resection, had no evidence of disease progression 12 months after the treatment.CONCLUSION: in mCRC with synchronous liver metastases, NACT according to the FOLFOXIRI regimen in combination with targeted agents with a moderate toxicity profile provide significant carcinocidal effect without having a negative impact in the perioperative period. The study is ongoing to analyze 2-year disease-free and overall survival of patients.

Introduction. Luminal breast cancer (BC) occupies the largest proportion in the structure of the entire molecular landscape of this disease. During the ongoing treatment, most often hormone therapy, in part of patients, the disease progression develops, which makes necessary the search for new molecular predictors. Aim of the research. To study the clinical and morphological features of the disease depending on BMI-1 and ROR1 expression in the primary tumor in luminal breast cancer patients during aromatase inhibitors therapy. Materials and methods. The study included 80 patients with T1-2N0-1M0 operable primary breast cancer at the age of 62.1 ± 8.1 years. The primary tumor tissue was studied using immunohistochemistry. Antibodies to ROR1 and BMI-1 were used. The presence and degree of immunostaining, and the percentage of positively stained tumor cells were assessed. The expression parameters of the studied markers were assessed in relation to various clinical and pathological data of the disease. Results. 70 patients had the luminal A subtype, 10 patients had the luminal B/HER2-negative subtype. Positive BMI-1 expression was observed in 64% of cases, ROR1 expression was less common and amounted to 24%. As tumor grade increases, the number of cases with positive ROR1 expression increases (p < 0.05). The level of proliferative activity (Ki67) correlated with positive ROR1 expression (ρ = 0.312, p = 0.03) and BMI-1 (ρ = 0.310, p < 0.031). In presence of metastases to regional lymph nodes, the expression of both markers was significantly higher. The occurrence of distant metastases is associated with high levels of BMI-1 expression by primary tumor cells (p < 0.05). Conclusion. The study clearly demonstrates the correlation of ROR1 and BMI-1 proteins with the clinical and morphological parameters of the primary tumor and the course of the disease in luminal subtypes of breast cancer.

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.

Whole exome sequencing of peripheral blood samples from Tuvan females diagnosed with breast and ovarian cancers (BC/OC) was performed to search for new genes involved in BC/OC pathogenesis. Considering the high cost of whole exome sequencing and study material requirements, 9 samples were selected from 61 genomic DNA samples. A mutation in the LGR4 gene (rs34804482) involved in the tumor-mediated Wnt signaling pathway and a mutation in the BRWD1 gene (rs147211854) involved in chromatin remodeling were identified in BC patients. A mutation in the CITED2 gene (rs77963348) involved in the pathogenesis of primary ovarian insufficiency was identified in a patient with OC and a history of infertility. A mutation in the PDGFRA gene (rs2291591) was identified in two BC/OC patients. LRG4, BRWD1, PDGFRA, and CITED2 germline pathogenic mutations were discovered in Tuvan women diagnosed with BC/OC for the first time.

Hereditary breast cancer (HBC) is a heterogeneous disease caused by mutations in genes characterized by ethnic specifcity. The clinical heterogeneity of this disease signifcantly complicates its diagnosis. The use of high-throughput sequencing is one of the approaches that allow the search for genes and their variants associated with the development of HBC. The purpose of the study was to search for new genes associated with HBC in the understudied ethnic groups of Siberia by using whole exome sequencing (WES).Material and Methods. WES was performed on a cohort of 16 probands with BC (Tuvan, Yakut, Altai ethnos). The study material was genomic DNA isolated from peripheral blood leukocytes. Libraries were prepared using a BGI Optimal DNA Library Prep kit. An Agilent SureSelect Human All Exon V6 kit was used for hybridization. High-throughput sequencing was performed on a DNA nanoball sequencing platform (DNBSeq-G400).Results. In the overall group of patients with signs of HBC, pathogenic variants were detected in 12.5 % of cases (2/16). For the frst time, BRCA1 (rs80357635) pathogenic variant was identified in a young patient with metachronous BC (Yakut ethnic group). A pathogenic variant of the ATM gene (rs780619951 NM_000051:exon16:c.C2413T:p.R805X) was identified in a young patient with BC (Tuvinian ethnic group). A pathogenic variant of the TDP2 c.G4T:p.E2X, rs770844602 gene (DNA repair gene) was identified for the frst time in a Tuvan BC patient (metachronous) with a family history, but its contribution to HBC remains to be proven. The TDG gene variant (rs764159587 NM_001363612:exon7:c.536dupA:p.E179fs) found in the Tuvan ethnic group and affecting splicing (SpliceAI: 0.580) requires special attention.Conclusion. This report is the frst to describe the germinal variant in the BRCA1 (rs80357635) gene in the Yakut ethnic group. Further studies are required to confrm pathogenicity of germinal variants in non-well studied genes TDP2, TDG in ethnic BC patients.

Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients. However, its efficacy is extremely limited in microsatellite stability (MSS)/mismatch repair proficient (pMMR) patients. We report a case of a 42-year-old man diagnosed with MSS/pMMR mCRC who has achieved a durable response to nivolumab after a progression under chemotherapy with antiangiogenic treatment. We observed for the first time an atypical response after 8 months of nivolumab treatment, with the regression of previous primary pulmonary lesions and the presence of new para-aortic lymph node lesions. This report demonstrates that a subset of pretreated mCRC patients with the MSS/pMMR phenotype may benefit from nivolumab and these patients need more attention.

Background: Hereditary breast cancer (BC) is an autosomal dominant disease caused by mutations in genes such as BRCA1/2, BRAD1, RAD54L, RAD51, ATM, BRIP1, and others. The prevalence and range of mutations can differ among various regions and ethnic groups. In a previous study using whole exome sequencing, we identified a germline pathogenic variant of the LGR4 gene (rs34804482, NM_018490.3: c.2531A>G) in a young Tuvan BC patient (belonging to the Turkic-speaking tribes of Central Asia). The aim of this study was to determine the frequency of the germinal pathogenic variant rs34804482 of the LGR4 gene (NM_018490.3: c.2531A>G) in ethnic groups of West Siberia (comparing BC patients and healthy subjects) using the PCR-RT method. Methods: The study involved 735 BC patients from various ethnic groups in Siberia, including Russians, Buryats, Tuvans, Yakuts, Altaians, and Khakassians, with a median age at diagnosis of 43±15.6 years. The control group consisted of 727 healthy women from the same ethnic groups in Siberia, with a median age of 43.05±13.5 years. Results: In a general group of BC patients, the frequency of the pathogenic variant of the LGR4 gene (rs34804482) was 0.027. Specifically, the frequency of this variant was 0.015 in Russian BC patients, 0.022 in Buryat BC patients, and 0.069 in Tuvan BC patients. This variant was not detected in Khakassian and Yakut BC patients. In Tuvan women with BC, the frequency of the pathogenic variant of the LGR4 gene was significantly higher than in Russian BC patients (X2 = 8.153, p = 0.005). The frequency of the pathogenic variant of the LGR4 gene (rs34804482) in healthy Tuvan women was significantly higher than in healthy Russian women (0.066 versus 0.016, X2=6.368, p=0.012). The mutation frequency in healthy Russians was close to that in Europeans (0.016 versus 0.0219). The highest frequency of this pathogenic variant was found among healthy Tuvans (0.066), significantly higher compared to Americans (0.0000) and other ethnic groups (according to ExAc). Conclusions: Our study was the first to investigate the frequency of the pathogenic variant of the LGR4 gene (rs34804482) in different ethnic groups of Siberia, comparing BC patients with healthy individuals. We found no statistically significant differences in the mutation frequency between BC patients and healthy individuals in the ethnic groups studied. The highest frequency of this pathogenic variant was observed among healthy Tuvans (0.066), which was significantly higher compared to other ethnic groups.

OBJECTIVE:The BRCA1/2 mutation status testing is the global standard of care for breast cancer patients with a family history of cancer. BRCA1/2 mutations are known to be ethno-specific. For some ethnic groups of the Northern Asia (Buryats, Yakuts, Altaians, Tuvans, Khakasses, etc.) the founder mutations in the BRCA1/2 genes have not been revealed. This systematic review was conducted to assess the prevalence of BRCA1/2 mutation in breast cancer patients inhabiting Eastern Europe and Northern Asia (or Siberia). METHODS:A total of 23,561 studies published between 2014 and 2024 were analyzed, of which 55 were included in the review. The literature search was conducted using RusMed, Cyberleninka, Google Scholar, eLibrary, NCBI databases (n=5) and conference papers. RESULTS:The founder mutations (c.5266dupC and/or c.181T>G) of BRCA1 gene that were frequently observed in the Slav peoples were also identified in Chechens, Armenians, Bashkirs, Ukrainians, Mordovians, Mari, Kabardians, Tatars, Uzbeks, Kyrgyz, Ossetians, Khanty indigenous peoples and Adygs. For Chechens, Kabardians, Ingush, Buryats, Khakasses, Sakha, Tuvans and Armenians, rare pathogenic variants of the BRCA1/2, ATM, СНЕК2, BRIP1, NBN, PTEN, TP53, PMS1, XPA, LGR4, BRWD1 and PALB2 genes were found. No data are available about the frequency of pathogenic BRCA1/2 mutations for ethnic groups, such as the Udmurts, Komi, Tajiks, Tabasarans, and Nogais indigenous people. CONCLUSION:This is the first systematic review that provides the spectrum of BRCA mutations in ethnic groups of breast cancer patients inhabiting Eastern Europe and Northern Asia. It has been shown that the mutations are ethnospecific (varied widely within groups) and not all groups are equally well studied. Further studies on the ethnic specificity of BRCA gene mutations are required.

Colorectal cancer has been one of the leading malignant neoplasms in males and females over many years. The vast majority of patients (70%) with colon lesions develop distant metastases to the liver, which are the main cause of death.

Triple-negative breast cancer (TNBC) is characterized by high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. Currently, four subtypes in the classification of triple-negative breast cancer (TNBC) are distinguished, which differ from each other in morphological manifestations, molecular genetic features, survival rates, prognosis parameters, and tumor resistance to therapy. A special place in this breast tumors group is occupied by the mesenchymal subtype, the frequency percentage of which varies from 7% to 28%, according to different data. The mesenchymal subtype of TNBC (M-TNBC) is characterized by the expression of molecular markers related to the epithelial-mesenchymal transition (EMT) program and cancer stem cells. M-TNBC has a highly aggressive behavior and worse prognosis due to its invasive and stem-like features, which correlate with metastatic dissemination and resistance to therapies. This review discusses the current knowledge regarding the mesenchymal TNBC subtype and its response to conventional therapeutic strategies. The complex approach to finding effective treatment options to restore immunocompetence in mesenchymal breast cancer patients is the final goal for further extended studies.

Background . Colorectal cancer (CRC) is one of the most common cancers and one of the most leading causes of cancer-related deaths worldwide. Approximately 35 % of CRC patients have liver metastases at the time of diagnosis. These patients have a poor prognosis, with the 5-year survival rate of 15 %. Given the poor survival with currently approved methods, the development of the optimal treatment options is needed. The purpose of the study was to search for data on the development of surgical techniques for the treatment of patients with metastatic CRC (mCRC) with isolated liver metastasis. Material and Methods . Literature search was carried out in Medline, Cochrane Library, Elibrary and Pubmed databases, including publications characterizing historical and modern results (from 1976 to 2021). Results . Liver resection in mCRC patients with isolated liver metastasis is the only treatment that offers a chance of increasing the 5-year survival rate up to 45–60 %. Radical surgery should include the removal of the primary tumor and all metastases with negative histological resection margins while preserving sufficient functional liver parenchyma. The paper discusses various approaches to surgical treatment of mCRC patients with liver metastases, with an assessment of their advantages and disadvantages, as well as presents data on perioperative and oncological outcomes. Conclusion . The surgical treatment strategy should be adapted for each mCRC patient with synchronous liver metastases. The core function of a multidisciplinary team is to determine the patient’s treatment plan combining surgery and systemic chemotherapy, which will improve the immediate and long-term treatment outcomes.

Growth factors signaling cascades and their interaction with the central regulatory targets of tumor cells and estrogens are considered as the main mechanisms of hormonal resistance in breast cancer. The integration of the transforming growth factor β1 (TGF-β1) and PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway may result in the activation of proliferation and, as a result, the development of an in-effective response to therapy and disease progression. The review summarizes a systematic analysis of the literature data on the role of TGF-β1 signaling in the mechanisms of tamoxifen resistance to in the aspect of interaction with the PI3K/Akt/mTOR. The interaction between the estrogen receptors α signaling and tamoxifen, the mechanisms of regulatory activation of TGF-β1 and PI3K/Akt/mTOR, as well as their contribution to the tamoxifen response are considered. The direct involvement of TGF-β1/PI3K in the mechanisms of tamoxifen resistance to determines the prospects for studying the effector of these cascades as molecular targets. The knowledge accumulated to date allows considering the TGF-β1/PI3K signaling pathway as a potential molecular tool for the search for effective strategies for blocking the resistance of tumor cells to tamoxifen.

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods . The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results . A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ 2 =43.7; p<0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found. Conclusion . Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype.

The aim: to study the expression status of ERα, TGF-βR2, pAkt to assess the breast cancer progression when prescribing drug therapy with tamoxifen. ESR1 gene expression level, TGF-βR2 and pAkt protein expression as well as the populations of pAkt–/TGFβR2+ cells were identified as additional molecular genetic markers for the prognosis of estrogen-positive breast cancer.

Metastatic colon cancer (mCC) is a heterogeneous disease, which significantly complicates its prognosis and the choice of an effective treatment strategy for patients. The use of mСС molecular profiling data will allow identifying an optimal approach to justify the choice of therapy and increase the patient’s survival rates.

Aim: to analyze outcomes of multimodal treatment including preoperative chemotherapy with FOLFOX 4 regimen in patients with upper rectal cancer.Patients and Methods: the pilot study included 24 patients. Stages II and III were confirmed in 2 (8.3%) and 22 (91.7%) patients, respectively. All patients underwent 3 cycles of chemotherapy in FOLFOX 4 regimen followed by surgery. In the postoperative period, patients with T4 and N+ underwent adjuvant chemotherapy administered over 6 months including the time of preoperative treatment.Results: all patients completed preoperative chemotherapy with the FOLFOX 4 regimen. The toxicity of chemotherapy was 38.9%; adverse events did not exceed grades I-II. Partial tumor regression (RECIST 1.1 criteria) was achieved in 18 (75.0%) patients. All patients underwent surgery 4 weeks after chemotherapy. Postoperative complications occurred in 4 (16.7%) patients, 1 (4.2%) had grade IIIb complication (Clavien-Dindo scale), which required re-surgery. Pathological complete response (TRG1 by Mandard scale) was revealed in 1 (4.2%) patient. Thirteen patients (54.2%) received adjuvant chemotherapy. The mean follow-up was 38 (17-54) months. Three patients (12.5%) developed local recurrence and 4 (16.7%) patients — distant metastases. The 3-year overall and diseasefree survival rates were 91.7% и 79.2%, respectively.Conclusion: multimodal treatment including preoperative chemotherapy with the FOLFOX 4 regimen was well tolerated and produced tumor regression with high 3-year survival rates in patients with upper rectal cancer.

Aim of the study: a systematic analysis of the modern literature data on the nivolumab monotherapy efficacy in patients with metastatic colorectal cancer (mCRC). Material and methods. The review summarizes the results of clinical studies of the nivolumab efficacy in patients with mCRC between 2012 and 2022. The current approaches to assessing the tumor response in patients treated with immune checkpoint inhibitors are considered, including response patterns and criteria. Results. Data analysis showed that the use of nivolumab in mCRC patients had significant clinical benefits. Nivolumab monotherapy was shown to improve survival in patients with high microsatellite instability (MSI) or deficiencies in mismatch repair (dMMR) that progressed during standard chemotherapy. Numerous clinical studies indicate the atypical response to nivolumab. Traditional response criteria, such as RECIST do not always adequately assess the therapeutic efficacy of nivolumab in patients with mCRC. Conclusion. To improve the efficacy of mCRC treatment, standardized approaches based on the proposed specific criteria for response to immunotherapy, including immune related RECIST, immune RECIST, and immune-modified RECIST must be developed.