The article presents two opinions regarding proton radiation therapy, its physical basis, dosimetric specifics and clinical efficacy in comparison with more traditional photon irradiation, as well as the authors» opinions concerning the expanding indications for proton therapy and the rationale for opening new centers for proton treatment in the world. This review has become a continuation of the discussion session on proton therapy held at the XXIII Russian Oncology Congress in November 2019.

Introduction: tyrosine kinases receptors (RTKs) play an important role in the pathogenesis of renal cell carcinoma (RCC). RTKs were studied on tumor and endothelial cells, but the presence of these receptors on lymphocytes was not confirmed. The objective of this study was to investigate the expression of tyrosine kinases receptors on lymphocyte subpopulations in healthy volunteers and RCC patients before and after removal of the primary tumor.

Materials and methods: the study included 19 patients with pT1‑T3N0 / N+M0 / M+ RCC, subjected to nephrectomy, and 10 healthy volunteers. Blood samples were collected once from healthy donors and twice from RCC patients, immediately before and 180 days after surgery. Isolation of lymphocytes and flow cytometry were carried out using standard methods. A comparative analysis of RTKs expression levels in peripheral lymphocytes from healthy volunteers and RCC patients, as well as in RCC patients before and after the operation, was carried out. A search was performed for correlations between the initial RTKs expression on lymphocytes from RCC patients and characteristics of the tumor development, as well as the disease prognosis.

Results: VEGFR-1, -2, -3, FGFR2, PDGFRα, β RTKs are expressed on CD45+ peripheral blood mononuclear cells, as well as subpopulations of CD3+ and CD8+ lymphocytes in healthy volunteers and untreated patients with RCC. No differences in the expression levels of all studied RTKs between subpopulations of lymphocytes were found in RCC patients (p > 0.05 for all). The level of RTKs expression on CD45+ peripheral cells in RCC patients before treatment is significantly lower than in healthy volunteers (p < 0.05 for all). The degree of a decrease in RTKs expression correlated with the pT status and the presence of tumor-associated venous thrombosis. A significant increase in the expression levels of VEGFR1 (on CB45+) and VEGFR2 (on CD8+, CD3+) (p < 0.05 for all) was noted 180 days after the removal of the primary tumor in patients with RCC. No other significant changes in RTKs production were identified. We were not able to determine the effect of RTKs expression on the RCC outcome.

Conclusions: lymphocytes express RTKs, their expression is more pronounced in healthy people than in patients with RCC. After surgical treatment, the RTKs expression becomes restored.

Introduction. The goal of the CLOVER study performed by the Russian Society of Clinical Oncology, was a pairwise comparison of three validated PD-L1 immunohistochemical (IHC) tests (Ventana SP142, Ventana SP263, Dako 22C3) in the patient population with non-small cell lung cancer (NSCLC). This study is the first large Russian comparative study to evaluate PD-L1 expression levels using immunohistochemistry methods.

Materials and methods. The study was conducted on 473 NSCLC samples from Biobank. The IHC tests were carried out with 3 antibody clones. Four trained pathologists independently evaluated the percentage of positively stained tumor cells (TC) and immune cells (IC). To assess the correlation of TC and IC between different runs and the prognostic values of one test for another, a concordant analysis was used.

Results. The number of PD-L1‑positive cells (≥1 %) was higher among IC compared with TC in all three IHC tests. Pearson correlation coefficients (PCC) for TCs were 0.71, 0.87, and 0.75 for 22C3 / SP142, 22C3 / SP263 and SP263 / SP142, respectively. PCC values for ICs were 0.45, 0.61, and 0.68 for the same pairs. A high coincidence of positive and negative results (>91 %) was obtained between the staining with antibodies 22C3 and SP263 of immunooncological agents in the 1st line.

Conclusions. The highest correlation between IHC tests was obtained by pairwise comparison of 22C3 and SP263. Clone 22C3 can be considered as a substitute for SP263 in the first-line treatment of NSCLC. Clone SP142 showed weaker expression in TC and IC compared to the other two tests in patients with non-small cell lung cancer.

Radiotherapy is one of the radical treatment options used in patients with prostate cancer (PC). Many studies of combined radiotherapy (CRT) for PC have demonstrated good results in respect of response to treatment; however, the sequence of CRT steps and optimal interval between them have not been determined so far. Few randomized studies have been conducted in order to confirm the advantages of brachytherapy at the first or second step or determine the most effective interval between the contact and external beam RT. Therefore, it appears reasonable to evaluate different CRT techniques.

Purpose. The goal of the study was to evaluate the outcomes of PC treatment depending on the sequence of CRT steps and the interval between them.

Materials and methods. 53 patients with PC received ¹²⁵I radiation therapy in combination with long-term hormone therapy (HT). Median follow-up was 38 months. Patients’ age varied from 54 to 81 years. All patients were in a high-risk group according to the D’Amico Risk Classification System. The patients were allocated to two groups: in Group 1, brachytherapy was used as the first step (n=31); in Group 2, it was applied after external beam therapy (EBT). The interval between the CRT steps could be less than 4 weeks (n=6), 4 – 7 weeks (n=17) and more than 8 weeks (n=30). Standard fractionation EBT with a total dose of 46 Gy using the VMAT technique was conducted. ¹²⁵I prostate implants were inserted to reach a total dose of 110 Gy. Neoadjuvant (2 – 4 months) and adjuvant (not less than 24 months) regimens of HT were applied.

Results. Five (9.4 %) patients had disease progression; two of them experienced only biochemical recurrence; distant metastases were diagnosed in three patients. Median time to disease progression was 29.9 months. One patient with a biochemical relapse died of acute myocardial infarction (1.9 %). Median five-year disease-free survival was 84.5±11.7 % in Group 1 and 83.5±9.1 (p=0.73) in Group 2. There were no significant differences in the incidence of toxicity depending on the sequence of CRT steps.

Conclusion. EBT using ¹²⁵I radiation sources in combination with long-term hormone therapy is an effective and safe treatment option for high-risk PC patients. No significant increase in the incidence of disease progression was observed when the interval between the CRT steps was increased to more than 8 weeks. Changes in the sequence of CRT steps do not affect response to treatment or incidence of radiation-related complications.

Primary malignant melanoma of the esophagus is a rare disease with an aggressive course and poor prognosis. This article presents a review of the world literature on this specific disease, including incidence statistics, modern principles of diagnosis and treatment, as well as a clinical case of a patient with resectable esophageal melanoma.

Extensive investigation of neuroendocrine tumors (NETs) has only started in recent years. The increased attention to this issue is due to the more frequent detection of NETs as a result of diagnostic methods improvement.

The limited effectiveness of chemotherapy for well-differentiated advanced metastatic NETs of gastrointestinal tract (GIT) and pancreas demonstrates the need for development of the new and more effective treatment options.

Recent studies on specific biological features of NETs have led to the development of the new targeted therapies which take into account high vascularization and overexpression of specific growth factors and related tyrosine kinase receptors. Thus, studying the mTOR TSC2, PTEN and PIK3CA signaling pathways opens up the new opportunities in the treatment of gastrointestinal or pancreatic NETs, especially in case of inoperable or metastatic tumors. Targeted therapy, which specifically inhibits growth factor receptors and related signaling pathways, is a promising approach to drug therapy for patients with gastrointestinal or pancreatic NETs.

This review summarizes the state of the art and prospects for using targeted therapy, and describes clinical studies in the treatment of gastrointestinal and pancreatic NETs.

Deficiency of the mismatch repair system is a unique molecular disorder that occurs in most types of tumors and leads to development of microsatellite instability (MSI) in them. The development of a hypermutated phenotype and related high immunogenicity are typically associated with more favorable prognosis as well as a high sensitivity to immunotherapy with inhibitors of immune checkpoint inhibitors. This review presents the current views on the diagnosis, prognostic and predictive significance of MSI in various tumors, as well as their response to immunotherapy.

The radical resection of all visible disease manifestations can significantly improve the prognosis of patients with metastatic colorectal cancer, however, complete metastasectomy is initially possible only in a small proportion of patients, with many of them subsequently developing relapse. Aiming to increase the number of patients subject to radical intervention and to reduce the recurrence risk, preoperative chemotherapy (with or without subsequent adjuvant treatment) is widely used in routine practice. In the hope of increasing immediate effectiveness (increasing the proportion of patients subject to R0 resection) and the long-term results of treatment, preoperative chemotherapy is often accompanied with biological agents (anti-EGFR and anti-VEGF monoclonal antibodies) continued after surgery in some cases. However, despite the evidence of increased resectability, the impact of this approach on long-term treatment outcomes has not yet been determined. The analysis of recent studies in this area doubts the safety of perioperative use of anti-EGFR antibodies in patients with potentially curable metastatic colorectal cancer.