В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Background Familial adenomatous polyposis (FAP) is a rare genetic disorder that is inherited in an autosomal dominant fashion. This disease is caused by a germline mutation in the APC gene, but in 20-30% of cases the disease occurs due to de novo mutations. There are several forms of the disease from severe, which is characterized by a pronounced number of polyps throughout the gastrointestinal tract (GIT) to a mild (attenuated) form of FAP, with less than 100 colonic polyps. According to various scientific literature, the risk of malignancy of epithelial formations reaches 100%. Identified epithelial formations of the gastrointestinal tract will lie down for endoscopic or surgical treatment. FAP is also characterized by neoplasms of extraintestinal localization, which characterizes it as a multisystem syndrome. There is a high risk of developing congenital retinal pigment epithelium hypertrophy, bone osteoma, fibroma, angiofibroma of the nose, thyroid carcinoma, hepatoblastoma, brain tumor and pancreatic tumor. Congenital retinal hypertrophy is the earliest extraintestinal manifestation of FAP. Thyroid cancer in young people, as a rule, is diagnosed first and serves as the basis for a comprehensive endoscopic diagnosis of the gastrointestinal tract. We present a rare case of FAP in a 14-year-old child associated with malignant neoplasms of extraintestinal localizations.

Background. Over the past 30 years, with the development of endoscopic technologies and the advent endoscopic ultrasound-guided fine-needle aspiration (EuS-FnA) it has become possible to diagnose with preliminary verification of cardiac tumors, which in turn is an undoubted advantage in detecting cardiac pathology. A rare clinical case is presented: the detection of a tumor of the left atrium using high-tech endoscopic techniques, in particular a EuS-FnA. when studying the surgical material using immunohistochemistry and FISH hybridization, the final diagnosis sounded like intimal sarcoma. Diagnosis of intimal sarcoma is a complex clinical task, and difficulties in making a diagnosis delay the duration of treatment. Our experience demonstrates the modern role of endoscopy as a minimally invasive method of diagnosing intracardiac tumors.

Aim. To evaluate technical features, safety and efficiency of radiofrequency ablation in tumor strictures of extrahepatic bile ducts. Materials and methods. An ongoing prospective observational study from September 2022 to June 2023 enrolled patients with unresectable extrahepatic bile duct tumors. Examination involved esophagogastroduodenoscopy, endoscopic ultrasound, retrograde cholangiopancreatography and video choledochoscopy with biopsy. Ductalradiofrequency ablation with polymeric or self-expanding metallic stent placement was applied as the main treatment method for the first time in Russia. Results. 3 patients (75 %) were diagnosed with cholangiocarcinoma of stage IIb–IIIa, 1 patient – with mucinous cystic tumor with signs of severe intraepithelial neoplasia. Radiofrequency ablation was successfully performed in all patients: tumor stenosis was completely eliminated, no complications reported in the immediate and distant period. The median follow-up period amounted to 8 months. Conclusion. The results of the first application of ductal radiofrequency ablation in unresectable tumors of extrahepatic bile ducts with stenosis prove to be positive. The method is considered to be effective, minimally invasive and safe.

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.

Introduction: Colorectal cancer is one of the leading malignancies in Russia [1]. The standard approach for selected patients (pts) with locally advanced colon cancer is surgery with adjuvant chemotherapy. Several studies have shown that colorectal cancer (CRC) with presence of a disorder in the mismatch repair (dMMR) / microsatellite instability (MSI) is characterized with high sensitivity to the immune checkpoint inhibitors. Several studies have shown that MSI / dMMR CRC patients tend to be more responsive to immune checkpoint inhibitors such as pembrolizumab, nivolumab or ipilimumab. However, there was no information about the efficacy of prolgolimab, a PD-1 receptor blocking antibody. Prolgolimab was highly effective in melanoma treatment, while the toxicity was comparable to pembrolizumab and nivolumab. Methods: We initiated the phase II non-randomized open-label clinical trial. Inclusion criteria were: histologically verified, MSI / dMMR, clinical stage II–III CRC. According to study protocol, prolgolimab (1 mg / kg) is administered every two weeks, then surgery should be done after 6 months of immunotherapy (12 cycles). In case of surgical treatment refusal, the systemic treatment proceeds for 1 year. The co-primary endpoint was the complete response (pCR) rate. Secondary endpoints included tumor regression grade by Mandard (TRG), major pathologic response (MPR), overall response rate (ORR) disease free survival (DFS) and overall survival (OS). Here is a presentation of safety and pathologic response data — rates of pCR / MPR, objective response rate. Results: A total of 26 patients began treatment with prolgolimab from April, 2022 to February, 2024. Immune-related adverse effects of grade III–IV, were recorded in 1 (3,8 %) patient (autoimmune hepatitis grade IV); 4 (15,4 %) patients had adverse effects grade I–II: autoimmune thyroiditis, diarrhea, hypothyroidism. Two patients were refused to make a surgical treatment because of clinical CR and possible volume of surgery. Nine (34,6 %) patients underwent surgical treatment within 3 months after the immunotherapy completion: 7 patients had TRG 1 and pCR, 2 — TRG 2 and MPR after the treatment. ORR was 100 %, complete clinical response rate 40 %. The study is still ongoing, DFS and OS will be announced in further publications. Median follow-up time was 5 months. Conclusion: The first interim analysis data suggest a strong potential for neoadjuvant immunotherapy to become standard of care and allow further exploration of organ-sparing approaches in MMR / MSI CRC patients.

Introduction. Melanoma is a malignant tumor that develops from melanocytes, has a high malignant potential and is characterized by early and aggressive metastasis. Just like with many other malignant neoplasms, melanoma can be clinically manifested by metastases in the absence of a primary focus. In the world and in Russia, there has been a steady increase in the incidence of melanoma over the past thirty years. Identifiation of the primary focus with an established diagnosis of metastases of a malignant tumor during life occurs no more than 25 % of cases. Even at autopsy, the primary focus is found on average in 15–20 % of patients, subject to a complete examination of the patient during his lifetime. The prognostic value of identifying the primary focus in melanoma remains unclear. Objective. To improve the diagnosis and treatment of patients with melanoma metastases without an identifid primary focus by assessing the signifiance of various factors, including the fact that the primary tumor was detected. Materials and methods. Since 2005 to 2019 at the National Medical Research Centre of Oncology n. a. N. N. Blokhin (Moscow, Russia) 196 patients with metastases of melanoma in the lymph nodes were observed and treated. Patient medical history were analyzed retrospectively and prospectively. All patients were followed up on an ambulatory after treatment. The inflence of the main clinical and morphological characteristics on the survival rates of patients was assessed. Patients with a morphologically confimed diagnosis of melanoma metastases in

Рак желудка (РЖ) характеризуется агрессивным течением и является одной из ведущих причин смерти от онкологических заболеваний. Стандартные схемы лечения не всегда эффективны при этом заболевании, поэтому разработка новых подходов терапии и поиск предиктивных маркеров представляется актуальной научной задачей. Перспективными терапевтическими мишенями при злокачественных новообразованиях являются иммунные контрольные точки (ИКТ). Для понимания патогенеза и оптимизации терапии активно исследуется вклад ИКТ в процессы опухолевой прогрессии. В данном исследовании на выборке пациентов с микросателлитно стабильным фенотипом опухоли РЖ были изучены уровни экспрессии генов ИКТ и их коэкспрессия с генами, вовлеченными в эпителиально-мезенхимальный переход. Проведена оценка ассоциации экспрессии этих генов с клиническими характеристиками РЖ. Показано, что для низкодифференцированных опухолей характерно понижение экспрессии генов CD276 и PVR (p<0,05). Также обнаружено, что развитие метастазов ассоциировано с повышением уровня экспрессии гена TDO2. В случае неметастатического РЖ была выявлена корреляционная связь между уровнями экспрессии генов CD44 и CD276. В группе метастатического РЖ корреляционная связь уровней экспрессии выявлена между генами ADAM17, PVR, CD276 и генами CD44, SNAI1. Полученные данные дополняют представление о молекулярно-генетических механизмах, регулирующих прогрессию опухоли, и могут внести вклад в разработку новых терапевтических подходов, предполагающих совместное ингибирование генов, коэкспрессия которых является особенностью данной нозологии. Gastric cancer (GC) is an aggressive tumor that is one of the leading causes of death from cancer. Treatment regimens are not often effective for this disease, so the development of new approaches to therapy and the search for predictive markers seems to be an urgent scientific task. Immune checkpoints (ICs) are promising therapeutic targets for malignant neoplasms. To understand the pathogenesis and optimize therapy, the role of ICs in tumor progression is being actively studied. In this study, IC gene expression levels and their co-expression with epithelial-mesenchymal transition-related genes were examined in a sample of patients with a microsatellite stable GC tumor phenotype. The association of the expression of these genes with the clinical characteristics of GC was assessed. It was found that the expression of the CD276 and PVR genes was reduced in low-differentiated tumors (p < 0.05). The development of metastases is associated with an increased level of TDO2 gene expression. In non-metastatic GC, a correlation was found between the expression levels of the CD44 and CD276 genes. In metastatic GC, a correlation of expression levels was found between the ADAM17, PVR, CD276 genes and the CD44, SNAI1 genes. The findings add to the understanding of the molecular genetic mechanisms that regulate tumor progression and may contribute to the development of new therapeutic approaches involving mutual inhibition of genes.

Malignant neoplasms (MNP) of the gastrointestinal tract in children are extremely rare and account for 1.2 % of all MNP. According to world literature, the incidence of gastric cancer is no more than 0.05 % of all cases of MNP of the gastrointestinal tract in children. In national and foreign literature, only isolated cases of stomach cancer in children and adolescents aged 10 to 18 years are described. Clinical manifestations of the disease, as in patients over the age of 18, are non-specific – epigastric pain, loss of appetite, weight loss, ascites, anemia, melena and others. In this regard, the diagnosis occurs at the late stages of the disease and, therefore, is characterized by an unfavorable prognosis. Gastric signet ring cell carcinoma (SRCC) is an uncommon histologic subtype of adenocarcinoma and usually occurs in people aged 20 to 40 years. We would like to report an extremely rare case of SRCC in a 14-year-old child.

Reactive blood changes are a heterogeneous group of pathological conditions that can occur in response to various conditions: viral, bacterial infections, helminth toxins, allergic agents. These reactions often require differential diagnosis with malignant neoplasms (MN) of the blood and hematopoietic organs (leukemias, lymphomas). It is important to note that only with a comprehensive examination of the patient with the involvement of a pediatric oncologist and hematologist, it is possible to exclude MN and carry out etiotropic treatment that contributes to the normalization of hemogram parameters. Article represents current data on the etiopathogenesis of leukemoid reactions, reactive thrombocytosis, secondary erythrocytosis and a clinical case observation of the development of a pseudoblast leukemoid reaction and reactive thrombocytosis against the background of an infectious process in a patient with Peutz-Jeghers syndrome, which will be of use to a wide range of pediatric practitioners.

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

Diagnosis of the genesis of bile duct strictures is a complex task facing clinicians. The use of cholangioscopy, in particular, the SpyGlass system, is becoming increasingly relevant among oncological patients in case of unsuccessful attempts at previous morphological verification. The presented clinical case demonstrates the capabilities of cholangioscopy as a method of direct visualization of the duct system with the ability to perform a biopsy under vision control in the verification of such a pathology as primary sclerosing cholangitis. Primary sclerosing cholangitis is a rare disease of the biliary tract that requires a systematic approach to diagnosis. The primary task is to identify the etiology of strictures and early diagnosis of cholangiocarcinoma.

Relevance. Pulmonary lesions of infectious etiology in oncohematological children are common and, in some cases, may be accompanied by a lethal outcome. When pulmonary tissue lesions on the background of hematopoiesis aplasia in the post-chemotherapy period is shown bronchoscopy to determine the genesis of the identified changes. Aim. To determine the diagnostic value of bronchoscopy with BAL in children with oncohematological diseases. Materials and methods. 25 bronchoscopies with BAL were performed on the basis of the endoscopic department of the Research Institute of Pediatric Oncology and Hematology. Results. According to the results of the study in 72% of cases a microbiologic agent was detected. The most frequent pathogens obtained by the results of cultures were Haemophilus parainfluenzae, Streptococcus oralis, Neisseria macacae, Streptococcus peroris and Pseudomonas aeruginosa. Conclusions. Bronchoscopy with BAL in children with blood system tumors is a highly informative method of pathogen detection and determination of the etiological cause of infiltrative-inflammatory changes in the lungs.

Background. The gastritis-like form of primary non-Hodgkin’s lymphomas (NHL) of the stomach is the rarest macroscopic variant of malignant neoplasms of the stomach, endoscopically resembling inflammatory changes in the mucous membrane and, in single observations, polypoid and flatly elevated forms of neuroendocrine tumors (NET) of the stomach. Despite the great experience gained in the diagnosis and treatment of primary NHL of the stomach and NET of the stomach, in clinical practice there are examples that cause difficulties in the correct interpretation of the endoscopic picture and the timely diagnosis. Aims. To analyze the data of a comprehensive endoscopic examination of patients with diagnoses of a gastritis-like form of primary NHL and NET of the stomach, and to identify the main differentially significant endoscopic criteria characteristic of each individual type of neoplasia. Materials and methods . In a prospective study conducted at the FSBI “N.N. Blokhin national medical Research Center of Oncology” of the ministry of Health of Russia in the period from 2017 to 2022, data from endoscopic and morphological studies of 69 patients with gastritis-like malignancies were analyzed. All patients underwent a comprehensive endoscopic examination of the upper gastrointestinal tract – esophagogastroduodenoscopy using all clarifying examination methods (narrow-spectrum mode, examination in magnification mode, a combination of narrow-spectrum examination with magnification mode), accompanied by the taking of biopsy material for the purpose of morphological verification of the diagnosis, and endosonographic study. Results. According to the results of a morphological study, the diagnosis of primary NHL of the stomach was confirmed in 38 patients (55.1 %), NET of the stomach – in 31 patients (44.9 %). A change in diagnosis based on the results of a morphological study occurred in 3 (4.3 %) of 69 (100 %) patients. The sensitivity and diagnostic accuracy of complex endoscopic examination were higher compared to endoscopic examination in white light mode, and amounted to 92.11, 95.65 and 13.16 %, 52.17 %, respectively. Conclusion. for a correct assessment of the endoscopic picture, it is necessary to conduct a comprehensive endoscopic examination using all clarifying diagnostic methods, which shows greater sensitivity and specificity compared to examination in white light mode.

Background. Radiofrequency ablation (RFA) of pancreatic NET up to 20 mm in size under endosonographic control (EUS) may become the method of choice in the treatment of this group of patients, as well as an option for analgesia in patients with locally advanced forms of pancreatic cancer. Aim. Describe the RFA – EUS technique, evaluate the safety and efficacy of the RFA – EUS method in the treatment of NET of the pancreas, up to 2.0 cm in diameter, and ablation of the celiac plexus in a cohort of patients with locally advanced forms of pancreatic cancer in order to relieve pain. Materials and Methods. In a prospective ongoing observational study conducted at the FSBI “N. N. Blokhin national Medical Research Center of Oncology” of the Ministry of Health of Russia from September 2022 to June 2023, data of 10 patients with resectable NET and unresectable malignant neoplasms of the pancreas were analyzed. The main method of treatment in 100 % of cases was RFA – EUS, performed for the first time in Russia. All patients at the first stage underwent esophagogastroduodenoscopy (EGDS) and endosonographic study with fine needle aspiration biopsy (EUS-TAB) to verify the diagnosis. At the second stage, all patients underwent RFA – EUS. The main evaluated parameter in the group of patients with NET was the absence of residual tumor tissue after RFA – EUS, according to Endo-US and MRI, the nature of changes in the pancreatic tissue after RFA was additionally assessed – fibrous or necrotic changes in the area of RFA – EUS. The main parameter evaluated in the group of patients with unresectable pancreatic cancer was the absence of pain within 8 weeks. and complete withdrawal from opioid analgesics 3–5 days after RFA – EUS. Results. According to the results of a morphological study, the diagnosis of pancreatic NET was confirmed in 7 (70 %) patients, adenocarcinoma – in 3 (30 %). Technical success, defined as a complete endosonographic and radiological response 3 months after the intervention in the group of patients with pancreatic NET (n = 7; 70 %) and complete withdrawal of opioid analgesics at 3–5 days, with the preservation of the analgesic effect for 8 weeks. after RFA – EUS, was achieved in 100 % of cases (n = 3; 30 %). Return to opioid analgesics after 3 months RFA – EUS in the group of patients with adenocarcinoma of the pancreas (n = 3; 30 %) was noted in 20 % of cases (n = 2), which required re-intervention, in 10 % (n = 1) – it was not possible to estimate the duration of the analgesic effect due to the death of the patient 2 months after RFA – EUS, the median follow-up was 6 months. Conclusion. The results of the study are the first experience of using RFA – EUS in the treatment of malignant neoplasms of the pancreas. EUS-guided RFA is an effective, minimally invasive and safe treatment for pancreatic NET, up to 2.0 cm in diameter, as well as an analgesic option for advanced pancreatic cancer. To determine the indications, contraindications and effectiveness of RFA in the radical and symptomatic treatment of malignant neoplasms of the pancreas, it is necessary to conduct large prospective multicenter studies.

Introduction. Malignant central airway obstruction and malignant tracheoesophageal fistula in the context of tumor development are potentially life-threatening conditions which usually require immediate intervention. Airway stenting is one of the safest and most effective methods of airway patency restoration in patients with malignant obstruction of the central airways and restoration of continuity in patients with malignant tracheoesophageal fistula.Aim. To evaluate the significance of self-expandable metal stents in palliative treatment of patients with malignant central airway obstruction and malignant tracheoesophageal fistula.Materials and methods. Between 2017 and 2021 at the N. N. Blokhin National Medical Research Center of Oncology, 55 patients were observed and treated and underwent trachea stenting per the results of bronchoscopy in combination with esophagogastroduodenoscopy. The 1st group included 25 patients with malignant tracheoesophageal fistulas, the 2nd group included 30 patients with malignant central airway obstruction.Results. In the 1st group, stenting was successful in 25 (100 %) cases which allowed to adequately seal the fistula. Stent migration was observed in 1 (4 %) patient with tracheoesophageal fistula in the context of stenosing cancer of the thoracic esophagus. In the 2nd group, stenting was successful in 30 (100 %) cases. Stent migration was not observed in this patient group. In both groups, there were no complications after stent implantation. Installation of tracheal stent allowed to improve patients’ quality of life and provide a possibility for successful special treatment through low-trauma manipulation.Conclusion. According to the obtained data, endoscopic trachea stenting is the most important method of palliative treatment of tumor-related trachea lesions with development of tracheoesophageal fistulas, malignant central airway obstructions and associated sub- and decompensated pulmonary insufficiency.

A distinctive feature of pancreatic cancer is its aggressiveness and rapidity. Neuroendocrine tumors are distinguished among neoplasms of the pancreas. Pancreatic neuroendocrine tumors are diagnosed on the basis of anamnesis, laboratory tests and the results of instrumental studies. However, the non-specific character of symptoms does not allow early detection of the disease. In a large proportion of patients, pancreatic neoplasms are diagnosed at stages III-IV. Radiofrequency ablation is an invasive intervention with the high temperature local effect on the tumor, resulting in the death of neoplastic cells. The method is based on the effect of high-frequency radio waves on pathological tissues. 6 radiofrequency ablations of neuroendocrine tumors of the pancreas under the control of endoscopic ultrasonography were performed at the N. N. Blokhin Oncology Research Center. There were no complications in the postoperative period. All patients were discharged with recommendations for supervision of an oncologist at their place of residence. It is also noted that such a method of treatment improves the further course of the disease and the life quality in patients.

Introduction : The results of six randomized control trials have been published by 2022, which evaluated the efficacy of adding PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer. However, it still remains unclear which patients derive the most clinical benefit from combined therapy. Therefore, it is necessary to evaluate the efficacy of the combination of anti-PD1 treatment with chemotherapy in different patient subgroups. Materials and methods : We conducted a meta-analysis of randomized controlled trials in patients with stage IV esophageal cancer who received anti-PD1 drugs with different chemotherapeutic regimens in the first-line setting to select patients who benefit the most from the combined therapy. Results : Six randomized trials were included in the analysis for a total of 3,813 patients. Patients who received combination therapy had significantly longer OS (HR = 0.69, 95% CI: 0.63-0.75; p < 0.001), PFS (HR = 0.62, 95% CI: 0.56-0.69; p < 0.001), and better ORR (OR = 2.12, 95% CI: 1.85-2.42; p < 0.001) than those who received chemotherapy alone. Subgroup analyses showed no benefit of adding PD1-inhibitors to chemotherapy in patients with PD-L1 CPS <1 in terms of OS (HR = 0.58, 95 % CI: 0.31-1.1; p = 0.1) as well as in never-smokers (HR = 0.9, 95% CI: 0.67-1.23; p = 0.52). Conclusions : The addition of PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer significantly improves treatment outcomes. Our results could not strongly suggest the selected patients' cohort which would benefit the most from the combination of PD-1 inhibitors and chemotherapy use.