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. The established approach notably improving the therapeutic outcomes for locally advanced gastric cancer and gastroesophageal junction cancer, presently entails the amalgamation of perioperative chemotherapy aligned with the FLOT protocol and surgical intervention. However, this approach harbors limitations, as only half of the patient cohort successfully completes the entire prescribed course of drug therapy. The potential solution to this problem lies in the complete transfer of the chemotherapy volume to the preoperative period and the execution of total neoadjuvant chemotherapy with FLOT regimen.Aim. Aim is to conduct a comparative assessment of the efficacy and safety between total neoadjuvant and perioperative chemotherapy with FLOT regimen for patients with locally advanced gastric cancer and gastroesophageal junction cancer.Materials and methods. In a retrospective study we enrolled patients with histologically confirmed locally advanced gastric cancer and gastroesophageal junction cancer meeting clinical stage criteria T2–4 and N0–3, without of distant metastases, treated between 2014 and 2020 at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation and Moscow City Oncologic Hospital No. 62 Department of Healthcare of Moscow. Participants in the control group underwent 8 courses of perioperative chemotherapy (4 preoperatively and 4 postoperatively), while those in the experimental group received 8 courses of total neoadjuvant chemotherapy. Both groups received drug therapy according to the FLOT protocol: 5-fluorouracil 2600 mg/m2 , intravenous drip, over 24 hours, leucovorin 200 mg/m2 , intravenous drip, oxaliplatin 85 mg/m2 , intravenous drip, docetaxel 50 mg/m2 , intravenous drip, on day 1, with a 14-day intercourse interval. The primary endpoint was one-year progression-free survival.Results. In the study included 187 patients. Participants were divided into two groups: 95 in the total neoadjuvant chemotherapy group and 92 in the perioperative chemotherapy group. The one-year progression-free survival was higher in the total neoadjuvant chemotherapy group at 79 %, compared to 68 % in the perioperative chemotherapy group (HR 0.54, 95 % confidence interval 0.32–0.9, p = 0.02). Median disease-free survival was 27.2 and 19.5 months in the neoadjuvant and perioperative chemotherapy groups, respectively. The tolerability of the entire planned drug treatment regimen was superior in the total neoadjuvant chemotherapy group, reaching 88.4 %, as opposed to 57.6 % in the perioperative chemotherapy group (p = 0.0001).Conclusion. Among patients with locally advanced gastric cancer and gastroesophageal junction cancer, the application of total neoadjuvant chemotherapy according to the FLOT protocol, administered over 8 courses, demonstrated enhanced one-year progression-free survival and improved tolerability of the entire planned treatment regimen.

Background: Nowadays there are no international recommendations regarding the necessity of repeated diagnostic laparoscopy (with cytological examination or without it) after preoperative chemotherapy for resectable gastric cancer Purpose: To determine the indications for the repeated laparoscopic surgery in gastric or gastroesophageal cancer patientsMaterials and methods: The information on 449 IB-III stage gastric cancer patients was analyzed. After 4 cycles of chemotherapy 52 patients underwent diagnostic laparoscopy with peritoneal fluid cytology testing.Results: The multifactorial analysis showed that tumor progression detected on CT scans and gastroscopy, subtotal gastric involvement (p < 0,014), and diffuse Lauren type (p < 0,026) were statistically significant negative prognostic factors after preoperative chemotherapy. The 8 weeks interval after neoadjuvant chemotherapy wasn’t significant.Results: The repeat staging laparoscopy after neoadjuvant chemotherapy is safe and may be considered for a certain category of patients.

Введение: Лечение больных псевдомиксомой брюшины — одна из сложных и нерешенных проблем в онкологии. В отечественной медицинской литературе тема псевдомиксомы брюшины представлена единичными разрозненными публикациями. В основных зарубежных национальных клинических руководствах данная тема также не освещена. Основными документами, определяющими подходы к лечению псевдомиксомы брюшины, являются национальные консенсусы. Настоящий Консенсус является первой попыткой предложить стандартизованные подходы к проблеме псевдомиксомы брюшины в России.Методы: Настоящий Консенсус принят на основании анализа литературных данных, анализа известных зарубежных консенсусов, а также в результате серии обсуждений с участием специалистов, имеющих значительный личный опыт в диагностике и лечении псевдомиксомы брюшины.Результаты: Итоговый документ Консенсуса представлен в формате расширенных клинических рекомендаций, освещающих все аспекты данной патологии — эпидемиологию, патогенез, классификацию, клиническую картину, диагностику, и возможные варианты лечения, наблюдение после лечения и организационные вопросы.Заключение: Настоящий Консенсус создан с целью предложить практикующим врачам оптимальную стратегию лечения псевдомиксомы брюшины, а также информировать врачей (как онкологов, так и общего профиля) об особенностях данной редкой патологии.

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.

Stereotactic body radiotherapy for early stage non-small-cell lung cancer was, is, and will remain the key subject of discussions between radiation oncologists and surgeons. Despite the positive treatment outcomes reported in some large studies on efficacy of the stereotactic radiotherapy, its use instead of surgery may not always be an unconditional decision. However, stereotactic radiotherapy opens new treatment options in patients who are inoperable or refused surgery. This is possibly due to the high accuracy of modern linear accelerators, which allow to reduce the toxicity of radiotherapy and achieve an almost identical overall survival rate compared to surgery.

Gastric cancer is one of the most common malignancies worldwide. Approximately 10 % of patients with gastric cancer are characterized by accumulation of gastric cancer cases in their family. The hereditary forms of gastric cancer account for 1–3 % of all gastric cancer cases. Hereditary diffuse GC syndrome is caused by germline mutations in CDH1 gene and determines a high risk of developing diffuse GC and lobular breast cancer. In this article, we present a clinical case of a 41-year-old patient with diffuse gastric cancer, who was found to be a carrier of novel germline mutation in the CDH1 gene. Next-generation sequencing (NGS) has facilitated an identification of CDH1 c.1596G>A genetic variant, thus enabling an accurate clinical diagnosis hereditary diffuse gastric cancer.

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.

Personalization of gastric cancer (GC) treatment is an urgent problem because of the clinical heterogeneity and aggressive course of the disease. Four GC subtypes were isolated based on molecular characteristics by The Cancer Genome Atlas researchers in 2014: Epstein-Barr virus positive (EBV+), microsatellite unstable (MSI), chromosomally unstable (CIN), and genomically stable (GS). There is no unified method to detect the CIN and GS subtypes today, while MSI and EBV status assessments are used routinely and are of great clinical importance. A total of 159 GC samples were tested for MSI, EBV DNA, and somatic mutations in codons 12-13 (exon 2), 61 (exon 3), and 146 (exon 4) of the KRAS gene; codons 597-601 (exon 15) of the BRAF gene; and codons 542-546 (exon 9), 1047-1049 (exon 20) of the PIK3CA gene. EBV+ GC was detected in 8.2% of samples; and MSI, in 13.2%. MSI and EBV+ were found to be mutually exclusive. The mean ages at GC manifestation were 54.8 and 62.1 years in patients with EBV+ and MSI GCs, respectively. EBV+ GC affected men in 92.3% of cases, 76.2% of the patients were older than 50 years of age. Diffuse and intestinal adenocarcinomas were diagnosed in 6 (46.2%) and 5 (38.5%) EBV+ cases, respectively. MSI GC equally affected men (n = 10, 47.6%) and women (n = 11, 52.4%). The intestinal histological type was the most prevalent (71.4%); the lesser curvature was affected in 28.6% of the cases. The E545K variant of PIK3CA was observed in one EBV+ GC case. A combination of clinically significant variants of KRAS and PIK3CA was found in all MSI cases. The BRAF V600E mutation, which is specific to MSI colorectal cancer, was not detected. The EBV+ subtype was associated with better prognosis. The five-year survival rates were 100.0 and 54.7% for MSI and EBV+ GCs, respectively.

Background . microsatellite instability (MSI) is a prognostic marker of survival in many malignant diseases and show resistance to chemotherapy at early stages of colorectal cancer and show no benefits from chemotherapy at early stages of colorectal cancer. However, the role of MSI in resectable gastric cancer (GC) remains unknown. Aim. To study the results of treatment of resectable gastric cancer with microsatellite instability. Materials and methods . The study included 286 patients with resectable gC who received treatment at the N. N. Blokhin national medical Research Center of Oncology. All patients underwent PCR testing for MSI-H in 5 markers (BAT25, BAT26, NR21, NR24, NR27). Tumor regression grades (TRG) were evaluated according to the mandard tumour regression score, including disease-free survival and overall survival. Results. MSI indicated in 27 cases (9.44 %) out of 286 resectable gastric cancer. In group patients who received only surgical treatment, 2-year disease-free survival in patients with MSI-H was 77.80 % versus 88.29 % in MSS patients (hazard ratio (HR) 1.82, 95 % confidence interval (CI) 0.37–8.82, p = 0.45), 2-year overall survival in patients with MSI-H was 88.90 % versus 95.36 % in MSS patients (HR 2.03, 95 % CI 0.20–19.8, p = 0.54). In patients who received perioperative chemotherapy, 28.57 % (4 / 14) had progression in MSI-H tumor versus 3.61 % (6 / 166) in MSS tumor (p <0.001). In group patients who received treatment combined with chemotherapy, 2-year disease-free survival in patients with MSI-H was 59.60 % versus 67.36 % (HR 1.96, CI 95 % 0.88–4.35, p = 0.09), 2-year overall survival in patients with MSI-H was 67.30 % versus 85.86 % in MSS patients (HR 1.86, 95 % CI 0.64–5.41, p = 0.25) Conclusion. MSI-H is not a favorable prognosis factor in patients with resectable GC who are treated surgically combined with chemotherapy. The prevalence of progression in patients with MSI-H-status is higher than MSS-status with perioperative chemotherapy (FLOT / FOLFIRINOX).

To date, gastric cancer patients still have a poor prognosis. Current endoscopic or surgical treatment modalities are radical only for early gastric cancer (T1). Curability dramatically declines as tumor invasion progresses and lymph node metastasеs appear. In Europe and North America, the 5-year overall survival rate of patients with stage T2–4 cancer is 20 % [1]. Combination therapy for gastric cancer is being extensively studied to improve the treatment outcomes [2–6]. Currently, perioperative chemotherapy with FLOT regimen is the mainstay of resectable gastric cancer treatment in Europe. FLOT4-AIO randomized study has shown that the FLOT regimen was associated with significant increase in the median overall survival (50 versus 35 months), disease-free survival (18 versus 30 months) and R0 resection rate compared to ECF / ECХ regimen.In this work we evaluated the efficacy and toxicity of perioperative FLOT regimen in patients with gastric cancer and gastroesophageal junction cancer type I–III cT4aN0M0, cT1–4N + M0, using a prospective database of patients treated at the N. N. Blokhin Russian Cancer Research Center.

Objective: analysis of the immediate and long-term results of surgical treatment of patients with lymph node (Ln) involvement in recurrent ovarian cancer (OC), as well as the search for prognostic factors for progression-free survival (PfS) and overall survival (OS).Materials and methods. The retrospective analysis included patients under the age of 75 who underwent surgery for recurrence of OC with Ln involvement at n.n. Blokhin national medical Research Center of Oncology in the period from 2005 to 2020. All patients had previously received combined treatment due to a primary diagnosis of OC. Exclusion criteria: the presence of concomitant pathology in the decompensation phase, primary multiple malignant tumors and recurrences of non-epithelial ovarian tumors. The analysis of the main operational characteristics, the frequency of postoperative complications according to Clavien–Dindo within 30 days after surgery, PfS, OS, as well as parameters affecting the long-term results of treatment were performed.Results. The study included 123 patients: a cohort of isolated lesions of the Ln (n = 65) and a group of combined recurrence in the Ln and other anatomical locations (n = 58). The frequency of complete cytoreduction was significantly higher in the group of patients with isolated recurrence in the Ln: 86.62 % versus 53.4 % in patients with combined relapse, p <0.0001. The median duration of the operation was also significantly higher in patients with combined recurrence: 245 min versus 180 min in a cohort of patients with isolated recurrence in the Ln, p <0.0001. Postoperative complications of grade III B were more often observed in the group of combined recurrence: 6.8 % versus 1.5 % in the group of isolated recurrence in the Ln, p = 0.148. none of the patients in the group of isolated recurrence in the Ln had postoperative mortality, while in the group of combined recurrence 2 (3.4 %) patients died after surgery from developed complications. In patients with isolated recurrence in the Ln and combined recurrence of OC, the median PfS was significantly higher when complete cytoreduction was achieved: 31.0 months and 18.0 months versus 10.0 months and 9.0 months with incomplete repeated cytoreduction, p <0.0001. In patients with isolated recurrence in the Ln and combined recurrence of OC, the median OS was identically significantly higher when complete repeated cytoreduction was achieved: 97.0 months and 60.0 months versus 34.0 months and 27.0 months with incomplete cytoreduction, p <0.0001.Conclusion. Surgical treatment of recurrence of OC is justified only if it is possible to achieve complete cytoreduction and platinum-sensitive type of recurrence of OC. Low grade tumor, platinum-sensitive type of recurrence, absence of marker recurrence of OC, isolated recurrence in Ln, complete repeated cytoreduction and lymphodissection were identified as predictors of PfS in multivariate analysis. The following factors had an independent favorable effect on OS in multivariate analysis: low tumor grade, platinum-sensitive type of recurrence, satisfactory overall status on the ECOg scale (0–1 points) at the time of detection of relapse, isolated recurrence in the Ln and complete repeated cytoreduction.

Despite the development of contemporary surgical management of retroperitoneal liposarcomas, local recurrence remains the major challenge in the treatment of these tumors. Currently, surgery is the main treatment option for liposarcoma. The international cancer community faces a global goal — the development of new combined treatment options for the treatment of retroperitoneal liposarcoma to reduce the postoperative recurrence rate and increase the overall survival. This article presents the world literature data on the treatment of retroperitoneal liposarcomas and demonstrates a case report describing treatment of a patient with this disease in the N. N. Blokhin NMRC of Oncology.

Currently, with duodenal tumor lesion (duodenum), the possibility of performing economical operations that significantly improve the immediate results and quality of life of patients is increasingly being considered as an alternative to gastropancreatoduodenal resection. using the example of clinical observation, the article presents a new type of economical surgical intervention – duodenectomy with preservation of the peripapillary flap. The operation was performed in a patient with cancer of the resected stomach with a low spread of the tumor along the wall of the duodenum. At the control examination 9 months after the operation, the patient’s condition is satisfactory, without signs of impaired biliodynamics and passage of food through the intestinal tube. The proposed method differs from the existing prototype (papilloservative duodenectomy) by preserving the peripapillary flap of the duodenal wall.The insertion into the jejunum of not the fater papilla, but the surrounding wall of the duodenum eliminates its deformation and violation of patency and provides greater reliability of the formed suture, and the preservation of the small duodenal papilla with an additional pancreatic duct of Santorini can help reduce the frequency of postoperative pancreatitis and pancreonecrosis. In addition to cases of low lesions of the duodenum in gastric cancer, the method can be used in patients with non-epithelial and neuroendocrine tumors, as well as in secondary tumor invasion of the duodenum from the outside. The criterion limiting the performance of this type of operation is the distance from the edge of the tumor to the fater papilla less than 2.0–2.5 cm.Duodenectomy with preservation of the peripapillary flap can be considered as a way to improve the safety and quality of life in the surgical treatment of patients with a tumor lesion of the duodenum.

According to the data of the world statistics, gastric cancer (GC) occupies the 5th place by morbidity and the 3rd one by mortality among malignant neoplasms. A significant proportion of patients are elderly patients, the proportion of which in real clinical practice can reach up to 60%. Ramucirumab is among the standards of second-line drug therapy both in monotherapy and in combination with paclitaxel. The feasibility of prescribing ramucirumab to patients with disseminated cancer of the elderly and its satisfactory tolerability is shown in a subgroup analysis of the REGARD and RAINBOW studies. The use of paclitaxel, included in the standard first-line regimens, may be limited by persistent neurotoxicity, a side effect of platinum derivatives. In this regard, the effectiveness of the combination of ramucirumab with the FOLFIRI regimen as a second-line therapy began to be studied. The article presents a clinical case of achieving a partial effect on the second-line therapy with ramucirumab with FOLFIRI regimen in a 74-year-old patient with HER2-negative gastric adenocarcinoma while registering rapid progression after 4 courses of first-line chemotherapy in XELOX regimen. Tolerability of the second line was acceptable: asthenia grade 1, stomatitis grade 1-2, neutropenia grade 3 were observed, so the irinotecan dose was reduced to 165 mg/m2. By June 2021, there were 10 28-day cycles of treatment, which is ongoing. The duration of disease control in the second line therapy was 11+ months, of which 9+ months – on the background of FOLFIRI regimen drug therapy with ramucirumab.

Objective: to study the state of cellular immunity in patients with gastric adenocarcinoma.Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 with stage I–III, 20 with stage IV) received surgical / combined treatment or independent chemotherapy, respectively, at the N. N. Blokhin National Medical ResearchCenter of Oncology. Peripheral blood sampling was carried out before starting treatment. We studied the cellular composition of peripheral blood, as well as systemic immunity parameters determined by flow cytometry (CD3+CD4+; CD3+CD8+; CD4+CD8+; CD4+/CD8+; CD3–CD16+CD56+; CD3–CD19+), and their prognostic significance in relation to overall survival and progression-free survival.Results. The prognostic value of the relative indicator of platelet lymphocytic index was determined: progression-free survival in patients with a high level of platelet-lymphocytic index (>208.7) was higher: 8.1 months versus 4.5 months (p = 0.0027). A favorable prognosis for overall survival was an increase in the number of CD3–CD19+ lymphocytes (hazard ratio (HR) 0.91; 95 % confidence interval (CI) 0.85–0.97; p = 0.007), and an unfavorable prognosis was an increase in the number of neutrophils (HR 1.26; 95 % CI 1.05–1.50; p = 0.012), platelet count (HR 1.01; 95 % CI 1.0–1.01; p = 0.043), as well as an increase in the number of NK cells (HR 1.04, 95 % CI 1.0–1.09; p = 0.029).Conclusion. Indicators of the cellular composition of peripheral blood, characterizing a systemic inflammatory reaction, as well as indicators of systemic immunity, can serve as additional prognostic factors for gastric cancer.

The purpose of the study was to systematize and summarize modern ideas about the role of hypoxia in the development of tumor radioresistance. Material and Methods . PubMed, eLibrary and Springer databases were used to identify reviews published from 1953 to 2020, of which 57 were selected to write our review. Results . Radiation therapy is one of the most important components in cancer treatment. The major drawback of radiation therapy is the development radiation resistance in cancerous cells and secondary malignancies. The mechanisms of cancer radioresistance are very complicated and affected by many factors, of which hypoxia is the most important. Hypoxia is able to activate the mechanisms of angiogenesis, epithelial-mesenchymal transformation and contribute to the formation of the pool of cancer stem cell, which are characterized by chemo- and radioresistance. In turn, the severity of hypoxia largely dependent on tumor blood flow. Moreover, not only the quantitative but also the qualitative characteristics of blood vessels can affect the development of tissue hypoxia in the tumor. Conclusion . A comprehensive assessment of the severity of hypoxia, as well as characteristics of angiogenesis and EMT can contribute to a better understanding of the mechanisms of development of cancer radioresistance.

Aim. To assess the immediate and long-term results of treating patients with bilateral lung cancer (LC).Patients and methods. Radically operated 5 patients with primary multiple synchronous LC (PMSLC) and 5 patients with primary multiple metachronous LC (PMMLC) were included in the study. Clinical and morphological data, results of instrumental studies, immediate and long-term treatment results were analyzed. Statistical analysis was performed using the Statistica6 software.Results. Tumors corresponding to T1‑T2 prevailed in both groups. At the same time, both in the PMSLC and PMMLC group, only in one case both tumors corresponded to T1–2N0M0, in the others — one or both tumors were with metastases in lymph nodes of the root or mediastinum. In early postoperative period, the number of surgical complications was 10%, somatic — 20%. All complications were successfully treated conservatively. Postoperative mortality was not observed. In PMMLC and PMSLC cases, one-year relapse-free survival (RFS) was 100% and 80%; two-year — 80% and 60%; three-year — 60% and 60%; four-year — 60% and 20%, respectively. The five-year RFS in patients with PMMPC was 40%. One patient with PMSLC was alive without relapse of disease for 4.5 years. Accordingly, one-year overall survival (OS) was 100% and 100%; two-year — 80% and 80%; three-year — 80% and 60%; four-year — 80% and 40%. Five- and six-year OS in patients with PMMLC were 60% and 20%, respectively.Conclusion. The absence of postoperative mortality and low number of postoperative complications indicate the safety of bilateral operations in patients with bilateral LC. Low rates of patients’ 5‑year survival are connected with problems of primary diagnostics and low efficiency of existing algorithms of regular medical checkup of patients with this pathology. To improve long-term results of LC treatment, it is necessary to more actively introduce the modern programs of dynamic observation and complex examination of patients, undergone surgery for LC, using the annual chest CT and fibrobronchoscopy.