Objective: To evaluate the impact of safety parameters and toxicity profile on the efficacy of first-line immuno-oncology (IO) — based therapy in patients with renal cell carcinoma (RCC) in real-world clinical practice. 

Materials and Methods: Inclusion criteria for this retrospective study were: age ≥ 18 years, histologically confirmed advanced RCC, and administration of first-line therapy with IO-based combination regimens. Exclusion criteria included contraindications to any combination therapy agents, lack of data on at least one administration of each combination agent, and absence of at least one follow-up examination after treatment initiation. All adverse events (AEs), their characteristics, and instances of treatment regimen modification due to AEs were documented, along with the best overall response to therapy, time to progression, time to death, and last follow-up. An analysis of the potential association between safety parameters and first-line therapy efficacy outcomes was performed. 

Results: Data from 194 patients were included, receiving either nivolumab with ipilimumab (IO — IO), 94 patients (48.5 %) or immuno-targeted therapy (IO — TKI) 100 patients (51.5 %). Median follow-up duration was 28.4 months (1–63 months). The objective response rate (ORR) in the entire population (IO — IO / TKI) was 36.6 %, disease control rate (DCR) was 79.4 %, median progression-free survival (PFS) was 20.0 months (95 % CI, 15.3–24.8), and median overall survival (OS) was 29.2 months (95 % CI, 24.4–34.0). In the IO — IO / TKI group, independent favorable prognostic factors for therapy efficacy were cutaneous AEs (risk ratio [RR] for ORR 5.9 [95 % confidence interval (CI): 3.1–38.4], p = 0.002; odds ratio [OR] for PFS 2.4 [95 % CI: 1.2–4.6], p = 0.011), endocrine AEs (RR for ORR 2.5 [95 % CI: 1.8–3.5], p = 0.021; OR for PFS 2.6 [95 % CI: 1.4–4.8], p = 0.002; OR for overall survival [OS] 2.6 [95 % CI: 1.5–4.6], p = 0.001), and gastrointestinal (GI) AEs (OR for PFS 1.8 [95 % CI: 1.1–3.2], p = 0.030). Independent unfavorable prognostic factors for OS were serious AEs (OR 24.9 [95 % CI: 4.7–130.5], p < 0.0001).Independent favorable prognostic factors in the IO — IO group were endocrine AEs (OR for PFS 2.1 [95 % CI: 1.1–4.1], p = 0.026; OR for OS 2.8 [95 % CI: 1.4–5.6], p = 0.003), while in the IO — TKI group, favorable prognostic factors included the occurrence of any AEs (OR for OS 2.9 [95 % CI: 1.1–7.5], p = 0.033), cutaneous AEs (RR for ORR 3.1 [95 % CI: 1.2–6.2], p = 0.04; OR for PFS 3.0 [95 % CI: 1.2–7.6], p = 0.021), GI AEs (OR for PFS 3.3 [95 % CI: 1.5–7.2], p = 0.002), and endocrine AEs (OR for PFS 3.3 [95 % CI: 1.6–6.7], p = 0.001).

Conclusions: The development of AEs in patients with RCC is associated with improved efficacy outcomes of IO based combination therapy. The potential use of AEs as biomarkers of clinical benefit from IO-based combination therapy warrants confirmation in prospective studies.

Study aim: The primary aim of the study was to evaluate the mutational profile of muscle-invasive urothelial car­cinoma (MIUC) using next generation sequencing (NGS). A secondary aim was to identify mutations that provide potential targets for anticancer therapy, while an exploratory aim was to identify the associations between the mutational profile and the course of the disease.

Materials: The study used tumor tissue and medical data from 50 patients with MIUC of the bladder (48 (96.0 %)) or renal pelvis (2 (4.0 %)). DNA and RNA alterations were studied in cells isolated from tumors with histologically confirmed invasive UC using NGS with a panel of 523 genes.

Results: The median age was 72 (51-87) years; the study sample included 43 men (86.0 %). MIUC was confirmed in all patients, either de novo (T2-T4a in 32 (64.0 %) patients, including 2 (4.0 %) patients with renal pelvis cancer) or as a result of progression of non-muscle-invasive bladder cancer (Tis-Tl in 18 (36.0 %) patients). Regional metastases were diagnosed in 8 (16.0 %) subjects, and distant metastases in 5 (10.0 %) patients. High grade UC was confirmed for 44 (88.0 %) samples (including concomitant carcinoma in situ in 4 (8.0 %) cases). The median tumor mutational burden (TMB) was 10.9 (0.0-49.6) muts / Mb (high TMB (> 10 muts / Mb) in 30 (60.0 %) out of 50 cases). The level of microsatellite instability was low in all samples; 244 therapeutically significant and oncogenic mutations in 84 genes were detected in 50 samples (median: 5 (1-11) mutations per sample). Level 1-2 pathogenic mutations were detected in 13 genes of 29 (58.0 %) samples (in > 1 gene in 13 cases (26.0 %)), with a frequency of>10% in the FGFR3 (9 (18.0 %)), TSC1 (9 (18.0 %)), PIK3CA (7 (14.0 %)), ERBB2 (6 (12.0 %)) genes. Level 3-4 mutations were identified in 12 genes of 33 (66.0 %) samples (in > 1 gene in 15 (10.0 %) cases), with a frequency of>10% in the KDM6A (19 (38.0 %)), ARID1A (12 (24.0%)) and MDM2 (7 (14.0%)) genes. Oncogenic mutations were detected in 63 genes of 46 (92.0%) samples (in > 1 gene in 37 (74.0 %) cases), with a frequency of >10% in the TP53 (25 (50.0 %)), FGF4 (5 (10.0 %)), RBI (6 (12.0 %)), CDKN1A, STAG2, FGF3, CCND1 genes (5 (10.0 %) samples with mutations for each). Invasive de novo UC is associated with a higher incidence of high TMB compared with recurrent UC (71.9 % vs. 38.9 %,p = 0.024) and a higher frequency of mutations in the PI3K signaling pathway genes (46.8 % vs. 16.7 %,p = 0.031).

Conclusion: MIUC is characterized by high TMB and low frequency of microsatellite instability. The most common mutations providing potential therapeutic targets are alterations of the FGFR3, TSC1, PIK3CA, and ERBB2 genes. De novo MIUC is associated with a higher frequency of high TMB and an increased frequency of mutations in the PI3K signaling pathway genes compared with invasive recurrence of non-muscle-invasive UC.

Background: The optimal treatment strategy for patients with stage III colon cancer remains a subject of active research. While adjuvant chemotherapy (ACT) following surgery is the current standard, the potential role of neoadjuvant chemotherapy (NeoACT) in improving treatment outcomes is increasingly being investigated.

Objective: To evaluate the impact of neoadjuvant chemotherapy (NeoACT) on surgical outcomes in patients with stage III colon cancer (Node-RADS scores 3-5).

Materials and methods: A prospective, single-center, randomized clinical trial included 108 patients divided into two groups: NeoACT (n = 54) and primary surgery (n = 54). Patients in the NeoACT group received chemotherapy using either the CapOX regimen (4 cycles) or FOLFOX6 (6 cycles), followed by surgery. Surgical outcomes (operation duration, intraoperative blood loss, conversion rate, postoperative complications according to Clavien-Dindo, and length ofhospital stay) and pathological findings were analyzed.

Results: NeoACT did not adversely affect surgical outcomes. The median operation time was 180 minutes, and the median hospital stay was 8.7 days. Intraoperative blood loss was 50-100 ml in both groups. A statistically sig­nificant increase in conversion from laparoscopy to laparotomy was observed in the NeoACT group (p = 0.046). The rates of Clavien-Dindo grade 3a — b complications were 4.2 % and 3.8 %, respectively (p = 1). NeoACT resulted in a higher rate of pNO (p < 0.001), reduced incidence of pT4b (p = 0.053) and pN2 (p = 0.06), and lower presence of lymphovascular invasion (p < 0.001). Only 59.3 % of patients in the NeoACT group required 3 months of ACT, compared to 71.2 % of patients in the primary surgery group who received 6 months (p < 0.001).

Conclusion: NeoACT does not increase the rate of postoperative complications and contributes to tumor down­staging, leading to reduced need for adjuvant chemotherapy. The inclusion of patients with Node-RADS scores 4-5 minimized the risk of overtreatment from 25% to 8%.

The aim of the study was to demonstrate the safety and satisfactory outcomes of surgical treatment in patients with ductal cancer of the body and tail of the pancreas with invasion of the main veins using distal subtotal resection of the pancreas with resection of the superior mesenteric and / or portal veins.
Materials and methods: Distal subtotal resection of the pancreas with resection of the superior mesenteric and / or portal veins was performed in 29 patients with ductal cancer of the body and tail of the pancreas. Parietal resection of the main veins with a length of 1.0 to 3.0 cm using a parietal suture was performed in 15 (51.7%) patients, and circular resection with a length of 1.5 to 5.0 cm was carried out in 14 (48.3%) patients. In the circular resection subset, 11 people had an end-to-end anastomosis, 2 had plastic surgery using a Gore-Tex synthetic graft, and 1    underwent an autologous vein plastic surgery. Compression of the portal vein during surgery lasted from 10 to 16 minutes with the creation of a direct end-to-end anastomosis and from 12 to 27 minutes with the use of a graft. Damage from the tumor to neighboring organs required a liver resection in 1 (3.5%) patient, wedge resection of the stomach wall in 3 (10.3 %) patients, adrenalectomy in 2 (6.9 %) subjects, small intestine resection in 2 (6.9 %) patients, one diaphragm resection, one nephrectomy, and one hemicolectomy. The duration of the operations ranged from 2 to 6.5 hours, and the volume ofblood loss ranged from 300 mL to 5.6 L. 
Results: R0 surgery was performed in 89.6 % of patients, R1 in 6.9 %, and R2 surgery in 3.5% of cases. Histopatho-logical examination of the surgical material revealed retroperitoneal invasion in 69.0% of patients, perineural invasion in 65.5%, and invasion of the superior mesenteric and/ or portal veins in 55.2% of cases. Complications occurred in 51.7% of patients, the incidence of Clavien-Dindo Grade III or higher complications was 34.5%. All complications were controlled with conservative treatment; there were no deaths. Long-term treatment outcomes: The one- and three-year overall survival rates were 74.6% and 14.9%, respectively (median 14.6 months), the progression-free survival rates were 31.0% and 15.5%, respectively (median 8.0 months). A comparison of results in 26 patients who underwent R0 surgery and 3 patients who underwent R+ surgery did not reveal statistically significant differences. 
Conclusion: Distal subtotal resection of the pancreas with resection of the superior mesenteric and / or portal veins is relatively safe and helps to improve the duration and quality of life of patients with ductal cancer of the body and tail of the pancreas.

The aim of the study was to determine the indications and evaluate the safety and effectiveness of preoperative embolization of the common hepatic artery in patients with the tumors of the pancreatic body and tail with celiac trunk invasion.

Materials and methods: Distal subtotal resection of the pancreas with resection of the celiac trunk and the common hepatic artery was performed in 32 patients. Of these, 8 had preoperative embolization of the common hepatic artery. The indication was the lack of adequate collateral blood flow through the pancreaticoduodenal arcades.

Results: Complete block of the common hepatic artery blood flow was achieved in all 8 patients who underwent preoperative embolization of the common hepatic artery, despite invasion of the celiac trunk. There were no com­plications during X-ray-guided endovascular intervention. A follow-up upper mesenteric angiography demonstrated adequate blood supply to the liver in all patients due to the development of collateral blood flow from the superior mesenteric artery territory. No ischemic complications in the liver were observed in the postoperative period, however, one patient had clinical manifestations of acute cholecystitis, which was relieved by conservative therapy.

Conclusions: Preoperative embolization of the common hepatic artery is a technically feasible and safe procedure that reduces the risk of ischemic complications in patients who have undergone distal subtotal resection of the pancreas with resection of the celiac trunk and common hepatic artery without angioplasty.

This literature review analyzes current approaches to the management of pregnant patients with breast cancer (BC) using sentinel lymph node biopsy (SLNB). SLNB represents a safe alternative to axillary lymph node dissection (ALND) in clinically node-negative patients, significantly reducing adverse surgical sequelae such as lymphedema and restricted mobility. The review presents the latest data on the use of radionuclide lymph node mapping with ^99mTc (in doses ≤ 10 MBq). Data confirming the safety of the procedure for the fetus, including the absence of an increased risk of congenital anomalies or pregnancy complications, are provided. The method, besides being safe, is comparable in effectiveness and outcomes to the non-pregnant patient group. The review discusses current clinical guidelines for treating pregnant patients, which generally support the use of this approach, recommending an individualized strategy. Multidisciplinary management involving oncologists, surgeons, and obstetrician-gynecologists is critically important to balance maternal treatment efficacy with fetal safety. Articles investigating the safety and efficacy of SLNB in pregnant patients were selected for inclusion in this review using the MEDLINE, UpToDate, Web of Science, and Scopus databases.

Epithelioid hemangioendothelioma (EGE) is an extremely rare vascular sarcoma characterized by unique morpho­logical and molecular features. The incidence is about 1 case per million people. This publication presents data on clinical cases with various localizations of EGE published in the Russian literature. Our unique clinical example of lung EGE is presented, which was accompanied by significant difficulties in histological verification. The paper analyzes the features of the diagnosis of this disease, as well as presents data on the treatment and its results.

The Russian consensus on prevention, diagnostics and treatment of gastric cancer was prepared on the initiative of the Moscow clinical scientific center named after A. S. Loginov on the Delphi method. Its aim was to clarify and consolidate the opinions of specialists on the most relevant issues of prevention, diagnostics and treatment of gastric cancer. An interdisciplinary approach was provided by the participation of leading gastroen­terologists, oncologists and surgeons.