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BACKGROUND: Currently there are practically no works in the literature to assess the outcomes of systemic therapy in patients with solitary, single and multiple metastases of renal cell carcinoma. AIM: The aim of the study was to analyze the outcomes of systemic drug therapy of the first line in patients with solitary, single and multiple metastases of renal cell carcinoma. MATERIALS AND METHODS: The data of 981 patients with metastatic renal cell carcinoma who underwent systemic therapy of the first line at the City Oncological Hospital No. 62 in Moscow and the City Oncological Dispensary in St. Petersburg from 2006 to 2022 were retrospectively analyzed. All patients underwent clinical, laboratory and pathomorphological examination. 90 (9.2%) patients had solitary metastases, 252 (25.7%) single metastases and 639 (65.1%) multiple metastases. An analysis was made of the outcomes of 1st line therapy, which were conditionally divided into favorable, including all cases of complete response, partial response and stabilization, and unfavorable progression during treatment, death or deregistration. Subsequently patients who had previously received chemotherapy or cytokine treatment were excluded from the analysis. RESULTS: Complete response (3.3%) and deregistration (5.56%) were more often observed in patients with solitary metastases, stabilization more often occurred in patients with single metastases (51.1%), partial response (9.4%) and death (6.2%) in patients with multiple metastases. In patients with multiple metastases treated with immune checkpoint inhibitors a partial response was observed in almost half of the cases. Stabilization and progression were observed in almost the same percentage of cases (about a quarter of cases), and only two patients had a fatal outcome, which is slightly lower than in patients receiving tyrosine kinase inhibitors. Frequent outcomes when using tyrosine kinase inhibitors were stabilization of the process (40.72% of cases) or progression (38.72%), a complete and partial response was rarely recorded. Significant differences in the occurrence of favorable and unfavorable outcomes were revealed in patients with multiple metastases, depending on the number of affected organs and the prescribed drug. When comparing the results of systemic therapy of the first line, a higher efficiency of tyrosine kinase inhibitors was observed in solitary metastases of tumors with a high and moderate degree of differentiation. Systemic therapy of G3 tumors with solitary metastases had low efficacy in the appointment of tyrosine kinase inhibitors in 27.27% of patients. Higher efficiency was noted in single and multiple metastases. The effectiveness of immune checkpoint inhibitors was revealed in 70.6% of patients with single and multiple metastases. CONCLUSIONS: When choosing systemic therapy for metastatic renal cell carcinoma in clinical practice, it is necessary to take into account such prognostic factors as histological variants, the degree of differentiation of the tumor and the number of affected organs.

651 Background: The objective of this work was to evaluate the molecular and genetic features of the NET gastrointestinal tract. Genomic sequencing of 30 tumor samples of the latest generation was carried out and the data obtained were evaluated. Methods: In total, 30 tumor blocks of patients with gastrointestinal NET were tested by the new generation sequencing (NGS) method. The following genes were analyzed: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CDK12, CHEK1, CHEK2, EPCAM, FANCL, MLH1, MSH2, NBN, NF1, PALB2, PMS2, RAD51B, RAD51C, RAD51D, RAD54L, STK11, TP53, POLE, KRAS, NRAS, BRAF, EGFR, ERBB2, PIK3CA, MET ex14, BAT25, BAT26, NR21, NR24, MONO27, KIT, PDGFRA, Pi3Ca. Preparation of libraries for sequencing was carried out using NimblGen SepCapEZ Choice. Sequencing was performed on the Illumina MiSeq device. Results: In the study cohort of patients whose tumor blocks were sent for examination by the NGS method, there were more women – 19 (63.3%) than men – 11 (36.7%). When analyzing the age of patients, it should be noted that among all age groups, elderly patients predominated (60-74 years according to the WHO classification, 2016) – 12 (40%). In the majority of patients – 10 (33.3%) – the primary tumor focus was localized in the pancreas, in 6 (20%) patients it was primarily affected stomach, 7 (23.3%) – small intestine. Other parts of the gastrointestinal tract were affected much less frequently: the colon – in 1 (3.3%) patients. According to the division according to the degree of differentiation of gastrointestinal NET10 tumors had a degree of differentiation G1 (33.3%), 16 -G3 (54.3%), 4– G3 (13.3%). In the tumor sample of a patient with gastric NET G1 (Ki 67 = 2%), POLE mutations were found: c.2276G > A, p.R759H and CHEK2: c.470T > C, p.I157T. Also, mutations MLH1: c.199G > A, p.G67R BRCA1: c.1881 were found in the tumor sample of another patient with gastric NET G2 (Ki 67 = 7%). Conclusions: To improve the survival rates of patients, it is worth paying special attention to the molecular genetic study of the NET gastrointestinal tract. It is molecular genetic profiling that can become the basis for building more individualized algorithms for treating patients. The results of this study allow us to count on the fact that when conducting a study on a larger cohort of patients with gastrointestinal NET, it is possible to obtain results that will expand our knowledge of this nosology and allow us to supplement the already available information about prognosis factors and predictors of response to treatment.

435 Background: The aim of the present study was to determine to the effect of HER2, dMMR, PD-L1 status in the primary tumor and in metastasis to the regional lymph node of GC patients. Methods: A total of 44 patients with primary loco-regional (N+) gastric adenocarcinoma were recruited, and two formalin-fixed paraffin-embedded (FFPE) tumor-containing blocks of each patient (one block with primary tumor and one block with metastasis to the regional lymph node)were selected for HER2, dMMR, PD-L1 (CPS) immunohistochemical (IHC) assay. Clinicopathological characteristics were recorded, and intertumoral heterogeneity of HER2, dMMR, PD-L1 IHC expression was determined. Results: The study included 19 women and 25 men, 30 patients had Laurén’s intestinal type of cancer, 14 had a Laurén’s diffuse type. In 5 patients (11.4%) overexpression of Her-2 neu was detected, and heterogeneity was detected in all five cases: in three patients with HER2 overexpression in the primary tumor, no overexpression was detected in the metastasis to the regional lymph node, in two cases overexpression was detected in the metastasis, while no overexpression was observed in the primary tumor. 2 patients showed signs of dMMR (4.5%), in one case, heterogeneity in dMMR status was also revealed: signs of dMMR in the primary tumor and its absence in regional metastasis (pMMR). Assessment of PD-L1 status was carried out using the CPS formula. Ten patients (22.7%) had a negative PD-L1 status (CPS=0) both in the primary tumor and in regional metastasis. Positive PD-L1 status in the primary tumor: in 24 patients CPS= 0-5 (54.5%), in 5 patients CPS= 5-10 (11.4%) and 5 patients CPS= 10 or more (11.4% ). Positive PD-L1 status in regional lymph node metastasis: in 24 patients CPS= 0-5 (54.5%), in 5 patients CPS= 5-10 (11.4%) and in 5 patients CPS= 10 or more ( 11.4%). In 5 cases (11.4%) marked heterogeneity in PD-L1 status between the primary tumor and its regional metastasis (1 case with dMMR heterogeneity). Conclusions: The research findings in this paper indicate that the intertumoral heterogeneity of HER2 overexpression is common in GC patients, We highly recommend multi-block HER2 assessment for accurate diagnosis of GC. Given the rarity of status detection dMMR, a study in a larger number of patients is required, however, our data also confirm the presence of heterogeneity in dMMR status, and probably the possibility of metastasis of a more aggressive pMMR clone. Heterogeneity in PD-L1 status is quite rare and amounted to only 11.4%, which also has important practical significance.