Introduction: The main current approach to the treatment of patients with resectable cancer of the stomach and gastroesophageal junction (GEJ) is perioperative FLOT chemotherapy. The mFOLFIRINOX regimen has been shown to be effective and safe in disseminated adenocarcinoma of the stomach and GEJ. This article presents preliminary results of the efficacy and safety assessment of perioperative FOLFIRINOX chemotherapy in patients with resectable cancer of the stomach and gastroesophageal junction.
Materials and Methods: The FOLFIRINOX / FLOT study is a phase 2 / 3 open-label, randomized trial. Study enrollment was started in January 2019 and is currently ongoing. The inclusion criteria are: histologically confirmed resectable adenocarcinoma of the stomach or gastroesophageal junction, Siewert types II–III, clinical stage cT4aN0M0, cT1–4N1–3M0 or cT2–4N0–3M0, with total or subtotal involvement of the stomach. The following regimens were used for perioperative chemotherapy: FLOT — docetaxel 50 mg / m² on day 1, oxaliplatin 85 mg / m² on day 1, leucovorin 200 mg / 2 on day 1, 5FU 2600 mg / m²  × 24 hours starting on day 1, or mFOLFIRINOX — irinotecan 180 mg / m² on day 1, oxaliplatin 85 mg / 2 on day 1, leucovorin 200 mg / m² on day 1, 5FU 250 mg / m² bolus on day 1 and then 2200 mg / m²  × 48 hours on day 1. The primary endpoint was 5‑year overall survival.
Results: All planned preoperative courses of chemotherapy had been administered to 25 (86 %) patients in the FLOT group (n = 29) and 22 (92 %) patients in the FOLFIRINOX group (n = 24). Four (12 %) and 2 (8 %) patients in the FLOT and FOLFIRINOX groups, respectively, discontinued the treatment. The surgical staging was used in 48 patients (91 %) (25 [86 %] in the FLOT group and 23 [96 %] in the FOLFIRINOX group). Complete tumor regression (Mandard grade 1) had been achieved in 4 patients (2 [7 %] in the FLOT group and 2 [8 %] in the FOLFIRINOX group). Postoperative complications were detected in 2 patients (8 %) in the FLOT group and 4 (17 %) in the FOLFRIRNOX group. Thirty-three patients (62 %) received all scheduled postoperative treatment courses (n = 19, 66 % for FLOT and n = 14, 58 % for FOLFIRINOX).
Conclusions: The preliminary results of the FOLFIRINOX / FLOT study showed comparable tolerability of the regimens and comparable complete pathological response rates. However, there was a higher incidence of postoperative complications detected among patients who received the FOLFIRINOX regimen compared to the FLOT group.

The aim of this work was to study the risk factors for metastasis to the central and lateral neck lymph nodes in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), especially in patients with Hashimoto’s thyroiditis (TH).
Methods: A retrospective analysis of 763 patients after thyroidectomy with bilateral central lymphadenectomy (CLE) was performed at the interterritorial Center for Endocrine Surgery in Krasnodar during the period from October 2011 to October 2021. All patients had official histological diagnoses of TH. To identify risk factors for metastasis (Mts) to the lymph nodes of the neck, a multifactorial logistic regression analysis was performed.
Results: In our study, 277 patients with SCLC and TC showed relatively low rates of Mts to the central lymph nodes (CLU) compared with patients with SCLC without TC (37.2 % vs. 54.7 %, P  140 IU / ml was established as the most sensitive and specific level for predicting MPCT based on the study. Antibodies to AT-TPO, age, tumor size, and multifocal tumor shape demonstrated the ability to predict Mts in the central nervous system in patients with PCT on the background of TC with a probability of 81.1 % based on a multidimensional model. TH was associated with an increased prevalence of multifocal tumor with invasion of the gland capsule.
Conclusions: TH detection demonstrated the reduced risk of metastases to the CLN in patients with PCT and MPCT and indicated a potential protective effect. We found that the prognostic model is applicable for predicting a multifocal tumor and metastasis to the central nervous system in patients with PCT and TH.

Recent studies have shown that triple-negative breast cancer (TN BC) is characterized by the highest mutational load and immunogenicity compared to other subtypes, as well as the degree of tumor-infiltrating lymphocytes (TILs) infiltration, which play an important role in the development of antitumor immunity and treatment response. A significant disadvantage of the standard immunohistochemical method for determining TILs is the inability to fully assess the subpopulation structure of the immune infiltration, including minor populations.
Aim: The evaluation of the subpopulations of breast cancer lymphoid infiltration in patients receiving neoadjuvant chemotherapy (NACT) and its influence on achieving a complete pathomorphological response (pCR = RCB 0).
Materials and methods: The study included 90 patients who received NACT in following regimen: AC (doxorubicin 60 mg/m²  + cyclophosphamide 600 mg/m² ) every 2 weeks, followed by 12 weekly infusions of paclitaxel 80 mg/m²  + carboplatin AUC2. The TILs subpopulations were evaluated in core-biopsy samples prior to the NACT in all patients. The analysis performed by flow cytofluorimetry. Clinical and immunological analysis was performed for the following 9 lymphocyte subpopulations: CD3+CD4+, CD3+CD8+, CD4+CD25^highCD127^{– / low}, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+, CD8+CD279+, CD4+CD279+.
Results: The frequency of pCR was 51,1 %. The total TILs content in groups with pCR and non-pCR (RCB 0 vs RCB I–III) did not differ statistically (p = 0.271). The subpopulations analysis for CD3+CD8+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+CD4+, CD3–CD19+, CD4+CD25+, CD4+CD25^highCD127^{– / low} and CD4+CD279+ revealed no statistically significant differences between the median values in the groups with pCR and non-pCR. A study of the CD8+CD279+ population showed a higher level of these cells in patients achieved pCR / RCB 0 (median 18,6 % vs 12,3 % with RCB I–III) (p = 0.033). With CD8+CD279+ above the median (high, > Me), the pCR frequency was 61 % vs 35 % in the subgroup with CD8+CD279+ less than or equal to the median (low, ≤Me). Despite the absence of statistically significant differences in the content of CD3+CD16+CD56+(NKT-cells) in groups with pCR and non-pCR (p = 0.091), numerical differences in medians were revealed: 9,9 % and 8,3 %, respectively. At the same time, with CD3+CD16+CD56+(NKT) > Me (high), the pCR frequency was 63 % vs 36 % in the subgroup with CD3+CD16+CD56 + ≤Me (low). When selecting a narrow subgroup (CD8+CD279+ high and CD3+CD16+CD56+ high), the frequency of pCR was 87,5 % vs 27,3 % in the group with both low indicators.
Conclusion: The high content of CD8+CD279+ and CD3+CD16+CD56+ in the tumor sample before the treatment start was a predictor of high sensitivity to NACT and is associated with a higher frequency of pCR.

Background: According to the World Health Organization (WHO) data, gastric cancer (GC) was the 5th most common cancer and the 4th leading cause of cancer death worldwide in 2020. Peritoneal metastases (PM) are associated with a poor prognosis and detected in 30 % of patients with locally advanced GC; the median overall survival in patients with PM is 3–6 months without any treatment and 6–12 months with the use of systemic chemotherapy. Delivery of appropriate chemotherapeutic drugs directly into the abdominal cavity increases the effectiveness of treatment without severe systemic side effects. Today, various forms of intra-abdominal chemotherapy of PM are used in the world.
Aim: To evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) and aerosol intraperitoneal pressure chemotherapy (PIPAC) in the treatment of GC PM.
Purposes: To review current domestic and foreign publications on HIPEC and PIPAC, to compare their efficacy.
Materials and methods: Articles in PubMed, Scopus, Web of Science databases were studied and analyzed for the key queries: “stomach cancer”, “carcinomatosis”, “peritoneal metastases”, “HIPEC”, “PIPAC”.
Conclusions: The best results were achieved when using PIPAC as preoperative chemotherapy, followed by cytoreductive surgery in combination with HIPEC. Both procedures are promising and require further study with multicenter randomized prospective trials to assess their therapeutic potential.

Purpose: To evaluate the proportion of BRCA1 / 2 mutations in patients with serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum in Russia, to evaluate the percentage of germinal and somatic mutations, to identify the spectrum of mutations in BRCA1 / 2 genes, to evaluate clinical and morphological features of the BRCA-associated ovarian cancer (OC).
Patients and methods: The study enrolled patients of 18 years and older with newly diagnosed serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum. Biological material (blood, tumor tissue) was collected, followed by molecular genetic analysis. The method of mutations detecting in the blood were: allele-specific PCR, high-resolution melting (HRM), Sanger sequencing method. Advanced genetic testing included the use of generation sequencing (NGS) and multiplex amplification of ligated probes (MLPA). The collection of clinical data, family history, clinical and morphological characteristics of the tumor was performed.
Results: 500 patients were included in the study, the evaluation of BRCA1 / 2 mutations was performed in 496 patients (99,2 %). The frequency of BRCA1 / 2 mutations in the Russian patient population was 28,4 % (n = 141 / 496). The incidence of germinal mutations was 23,5 % (n = 117 / 141), and somatic — 4,8 % (n = 24 / 141). Frequent mutations in the Russian population were identified in 50 % of cases. When analyzing the ethnicity of patients in the Russian Federation BRCA-associated OC was most common in Russian (83,6 %, n = 118 / 141), Ukrainian (4,2 %, n = 6 / 141) and Tatar (3,5 %, n = 5 / 141) women. A family history of cancer was detected in 44 % of patients (n = 62 / 141) with BRCA1 / 2 mutations.
Conclusions: Due to the high frequency of germinal and somatic BRCA1 / 2 mutations in the Russian patients it is recommended to conduct the advanced testing methods not only in blood samples but also in tumor tissue.

Pancreatic cancer is an aggressive disease with an extremely unfavorable prognosis. The only effective method of treatment for this cancer is chemotherapy. The introduction of combined chemotherapy regimens and the development of molecular oncology in recent years have changed approaches to the treatment of this tumor. This review presents current literature data, as well as the data from the N. N. Blokhin National Medical Research Center of Oncology, concerning modern aspects of the treatment for metastatic pancreatic cancer.

Patients with locally advanced gastric cancer are at high risk of peritoneal dissemination. Poor prognosis after surgical treatment is mostly associated with presence of free tumor cells in peritoneal cavity that were not identified during pre-surgery examination. Staging laparoscopy and peritoneal washing with cytological examination are now routinely used to detect peritoneal carcinomatosis and for an accurate cancer staging.
Yet there is no standard treatment for patients with morphologically confirmed peritoneal dissemination of gastric origin. International oncological associations such as NCCN, ESMO and AJCC identify presence of free tumor cells in peritoneal cavity as distant metastasis where palliative chemotherapy is recommended as the only treatment option. Literature review shows that even if complete regression of micrometastases is achieved after chemotherapy alone, survival rate of this group of patients remains poor.
Today some authors prove combined treatment strategies for patients with peritoneal micrometastases of gastric origin to be effective. Because of the limited number of patients included in these studies there is no specific combined treatment scheme that can be recommended as a standard protocol of treatment patients with advanced gastric cancer.

Colorectal cancer ranks third among all cancers. More than 1 million cases are registered annually in the world, half of which are fatal. The investigation of the molecular genetic mechanisms of tumors’ development is relevant, which is an important contribution to the prospect of determining the prognosis and treatment tactics. This review presents the current classification of the mechanisms of tumor progression in colorectal cancer.

There is an increase in the number of patients with secondary malignant neoplasms. In addition, in some subgroups after radical cancer treatment, the lifetime risk of developing secondary malignant neoplasms can be as high as 33 %. Secondary malignancies remain an important cause of death in patients who have received radical cancer treatment. The presented clinical case demonstrates the risk of developing primary multiple malignant neoplasms after radiation therapy and chemotherapy. A 39‑year-old patient with diffuse large B-cell non-Hodgkin lymphoma underwent definitive treatment including chemo-and radiotherapy. Ten years later, the patient developed the induced multiple malignant tumors: a malignant neoplasm of the heart — myofibrosarcoma of the right ventricle with invasion of the anterior wall of the right ventricle Stage IIIB G2T3N0M0, left breast cancer Stage IIIA T3N2M0. The choice of treatment tactics for this category of patients remains particularly difficult.

Background: Germinal pathogenic variants are the cause of the development of hereditary cancer syndromes (HCS). Various genetic tests are used for HCS detect, from the «frequent» mutations of one or several genes analysis to the full-length gene sequence, next-generation sequencing (NGS) based panel, whole exome (WES) or whole genome sequencing (WGS).
There are some HCS cases with atypical clinical manifestations and the family history does not allow one to suspect a specific HCS and limit oneself to the study of only one or a few genes. Conducting research using NGS to assess the selected sample of cancer patient’s genetic characteristics has revealed atypical HCS cases.
Aim: To present the WGS diagnosis results for two atypical hereditary tumor syndromes cases.
Materials and methods: DNA isolation was performed using Qiagen DNA Isolation kit. WGS for all samples was performed at DNBSEQ-T7 (MGI) and DNBSEQ-G400 (MGI) sequencing platforms using PCR-free protocol with average sample coverage 30x. A standard bioinformatics analysis pipeline was implemented for all the samples data processing.
Potential clinically relevant variants were validated using Sanger sequencing. For all patients was received signed a written consent.
Results: In the first case report, a pathogenic variant in the TP53 gene was identified: c. 637C > T, p. Arg213Ter, rs397516436, and Li – Fraumeni syndrome was confirmed. In the second case, we detected two pathogenic variants carrier — BRCA2: c. 6644_6647del, p. Tyr2215SerfsTer13, rs80359616 and MSH2: c. 1906G > C, p. Ala636Pro, rs63750875 associated with hereditary breast and ovarian cancer and hereditary colorectal cancer (Lynch syndrome).
Conclusion: NGS, including WGS makes it easier to identify all clinically significant germline variants associated with hereditary cancer syndromes in cancer patients, as well as to trace their segregation in relatives.