Dynamics of Soluble Forms of the Immune Checkpoint Components PD-1/PD-L1/B7-H3, CD314/ULBP1, and HLA-G in Peripheral Blood of Melanoma Patients Receiving Blockers of Programmed Cell Death Protein PD-1.

The content of the soluble forms of immune checkpoint components sPD-1, sPD-L1 in blood serum, and sB7-H3, sCD314, sULBP1, sHLA-G in blood plasma of 30 melanoma patients receiving immunotherapy with anti-PD-1 antibodies (nivolumab, pembrolisumab) was measured before and in 4 and 8 weeks after the start of immunotherapy. The control group comprised 70 practically healthy donors. Standard immunoassay kits were used. In melanoma patients, the levels of sPD-L1 and sB7-H3 were significantly higher than in the control group (p<0001), sPD-1 level did not differ from the control, while sCD314 and sHLA-G levels were insignificantly decreased. During therapy, opposite changes in the levels of markers in individual patients were observed, and frequently after the initial increase (or decrease) after the first 4 weeks normalization did occur in the further 4 weeks. No statistically significant associations between the initial levels of markers and direction of their changes during treatment were found, but some trends indicating to the potential benefits from assessment of soluble forms of immune checkpoint proteins for evaluation and monitoring of the efficiency of the therapy with immune checkpoint blockers were revealed: significant decrease of sB7-H3 and sPD-1 levels in the course of treatment, higher initial sPD-1 level in patients with future progression than in those with stabilization or partial effect, and lower progression frequency in patients with increasing sPD-1 and sPD-L1 levels than in those with decreasing markers levels.

[Clinical efficacy of rehabilitation measures in patients with melanoma of the skin undergoing immunotherapy]. / Klinicheskaya effektivnost' reabilitatsionnykh meropriyatii u patsientov s melanomoi kozhi, nakhodyashchikhsya na immunoterapii.

BACKGROUND: Currently one of the urgent problems of oncology is he choice of tactics of rehabilitation measure. Despite the long list of known possible side effects from antitumor therapy, most patients do not receive follow-up and preventive interventions necessary to correct clinically significant consequences. OBJECTIVE: Analysis of clinical effectiveness of complex rehabilitation programs in patients with melanoma of skin receiving immunotherapy. MATERIAL AND METHODS: The study included 109 patients with metastatic melanoma, aged 26 to 88 years, who received immunotherapy in the period from 2019 to 2022. The study group (n=54) included patients who received a comprehensive rehabilitation program: physical therapy, nutritional support, general magnetotherapy, psychotherapy sessions without concomitant medications. Patients who did not use rehabilitation programs made up the control group (n=55). The effectiveness of therapy was evaluated in accordance with iRECIST 1.1 criteria. Immuno-mediated toxity of treatment was evaluated according to CTCAE criteria (version 5.0, 2017). To assess the quality of life (QoL), the EORTC QLQ-C30 questionnaire was used. RESULTS: The median follow-up of patients was 20 weeks in the study group, 19 weeks in the control group. Stabilization of the disease was achieved in 21 (38.9%) patients of the study group and 23 (41.8%) patients of the control group; disease progression in both groups was comparable: 10 (18.5%) - in the study group, 12 (21.8%) - in the control group. Adverse events of therapy were detected in 39 (72.2%) patients of the study group, 46 (83.6%) patients of the control group. All registered adverse events according to CTCAE 5.0 criteria were of grade I-II. No serious adverse events of the IV degree were detected during the study period. CONCLUSION: The introduction of comprehensive rehabilitation programs in the treatment of patients with melanoma shows its effectiveness and reduced toxicity of immunotherapy, however, there are a number of important issues that require further resolution.

[The role of nutrition status correction in the rehabilitation of cancer patients]. / Rol' korrektsii nutritivnogo statusa v reabilitatsii onkologicheskikh patsientov.

Metabolic changes due to the progression of malignant neoplasms and the negative consequences of aggressive methods of its treatment lead to a decrease in food intake in patients, which contributes to the development of anorexia-cachexia syndrome in cancer patients due to complex interactions between pro-inflammatory cytokines and host metabolism. Within the framework of this article, the author analyzes the possibility of the influence of nutritional status in cancer patients. The analysis of the results of the study of a group of cancer patients with various nutritional statuses was carried out. It is concluded that the control and correction of nutritional status should become an integral part of the assessment of the quality of life and meet the needs and expectations of the patient.

[Comprehensive rehabilitation of immune-mediated adverse events in cancer patients receiving checkpoint inhibitor therapy]. / Kompleksnaya reabilitatsiya immunooposredovannykh nezhelatel'nykh yavlenii u patsientov so zlokachestvennymi opukholyami, poluchayushchikh terapiyu ingibitorami kontrol'nykh tochek.

OBJECTIVE: To evaluate adverse events and clinical effectiveness of complex rehabilitation programs in patients with malignant tumors receiving checkpoint inhibitor therapy. MATERIAL AND METHODS: The study included 144 cancer patients who received immunotherapy for the period from 2019 to 2021. Group 1 consisted of 72 patients who received a comprehensive rehabilitation program including physical therapy, diet therapy, psychotherapy, general magnetotherapy. Patients of the second (control) group (n=72) did not receive rehabilitation procedures. Effectiveness of treatment was evaluated according to RECIST 1.1 criteria, safety of treatment - according to CTCAE criteria (version 5.0, 2017). To assess the quality of life (QoL), the Russian version of the EORTC QLQ-C30 questionnaire was used. RESULTS: Mean follow-up period in the first group was 4.5 months, in the control group - 5 months. Disease progression was observed in 35 (48.6%) patients of the main group and 32 (44.4%) patients of the control group. Two (2.8%) patients in the control group demonstrated complete response to therapy. Partial response was established in both groups in 13 patients (18.1%). Stabilization of disease was detected in 24 (33.3%) and 25 (34.7%) patients, respectively. Adverse events were registered in 54 (75.0%) and 60 (83.3%) patients, respectively. Adverse events grade III-IV occurred in 9.7% and 11.1% of patients, respectively. CONCLUSION. I: Mmunotherapy combined with comprehensive rehabilitation program confirms high effectiveness of these drugs. We observed good tolerability of rehabilitation procedures that do not deteriorate the course of the underlying disease. However, there are certain important issues, in particular influence of rehabilitation procedures on tolerability of immunotherapy in patients with cancer.

[Magnetotherapy in patients with malignant tumors receiving immunotherapy]. / Opyt primeneniya reabilitatsionnoi magnitoterapii u patsientov so zlokachestvennymi opukholyami, poluchayushchikh immunoterapiyu.

OBJECTIVE: To analyze the quality of life in patients receiving immunotherapy and overall response rate in case of additional magnetotherapy. MATERIAL AND METHODS: The study included 3 cohorts of patients (n=48) with various disseminated malignancies (melanoma, lung cancer, kidney cancer) who received immunotherapy. In the study groups, all patients additionally took courses of rehabilitation based on magnetotherapy. In the control cohorts, patients underwent courses of immunotherapy without additional magnetic therapy. Treatment efficacy was assessed according to iRECIST 1.1 criteria. The Russian version of the EORTC QLQ-C30 questionnaire was used to study the quality of life. We analyzed adverse events using the CTCAE 5.0 criteria. RESULTS: In patients with melanoma, the most common response to systemic treatment was stabilization (41.7% in the study group and 30.8% in the control group). The objective response rate was higher in the study group (33.3% vs. 23.1%). There was also significant improvement in the quality of life after treatment in the study group (by 23.5%). In the control group, the indicator worsened by 4.8%. Overall health improved by 12.8% in the study group and 10.3% in the control group. In patients with lung cancer, response to systemic treatment with stabilization was achieved in 33.3% of patients in the study group and 20% of patients in the control group. The objective response rate was 33.3% and 20%, respectively. Analysis of the study group revealed improvement of overall health by 9.6% and overall quality of life by 38.6%. In the control group, overall health improved by 4.8% and quality of life remained the same. In patients with kidney cancer, the objective response rate was 40% and 42.9%, respectively. Disease stabilization was achieved in 40% and 28.6% of patients, respectively. Overall health improved by 16.7% and 6.3%, overall quality of life - by 19% and 9.1%, respectively. CONCLUSION: Magnetic therapy during the course of immunotherapy improved the overall quality of life and reduced severity of adverse events. Further study of magnetotherapy as an accompanying rehabilitation technique is required.

Soluble forms of PD-1/PD-L immune checkpoint receptor and ligand in blood serum of breast cancer patients: association with clinical pathologic factors and molecular type of the tumor.

Results of enzyme-linked immunosorbent assay of the soluble forms of PD-1/PD-L immune checkpoint receptor and ligand (sPD-1 and sPD-L1) in pretreatment blood serum of 88 breast cancer patients at various disease stages aged 30-83 years are presented. The control group included 55 practically healthy women aged 19-82 years. Serum sPD-1 and sPD-L1 levels in breast cancer patients highly significantly (p<0.0001) differ from control and these changes are opposite: soluble receptor level is more than 6-fold decreased, while soluble ligand concentration - 5.5 fold increased. Both markers separately, as well as their ratio demonstrate very high sensitivity (94-100%) and specificity (95-100%) in relation to healthy control. No statistically significant associations of sPD-1 and sPD-L1 levels with clinical stage, individual TNM system criteria, tumor histological structure, grade, receptor status, and molecular type were established. In particular, no significant peculiarities of the markers' levels in triple negative breast cancer successfully treated with anti-PD-1/PD-L1 preparations were revealed. Long-term follow-up and dynamic studies of sPD-1 and sPD-L1serum levels in the course of treatment are required for evaluation of their independent from clinical and morphological factors prognostic significance and the possibility of application as low invasive tests for prediction and monitoring of corresponding targeted therapy efficiency.

[Clinical and economic analysis of the feasibility of using Dicarbamine for the prevention of the toxic effects of antineoplastic chemotherapy].

The aim of the study was to conduct clinical and economic analysis of the feasibility of using Dicarbamine for the prevention of toxic effects of chemotherapy. There were compared the direct medical costs on prevention and treatment of febrile neutropenia in 2 groups of breast cancer patients: chemotherapy alone in TAC mode or chemotherapy in the same way against oral Dicarbamine. Total costs due to hematologic toxicity were 1003945 rubles in the control group (22817 rubles on average by 1 patient) and 658980 rubles in the group treated with Dicarbamine (14 644 rubles on average by 1 patient). Also, the study found that in the group treated by Dicarbamine there were lower rates of dose reduction and delay of the next course of chemotherapy, which might have an impact on other costs arising from cancer. The results of this study demonstrate the clinical and economic feasibility of using Dicarbamine for the prevention of hematotoxic complications of chemotherapy.

[Support of hematological homeostasis during chemotherapy with taxanes].

Study group consisted of 84 oncological patients with various tumor localization that received chemotherapy with taxanes. Medium follow up was 32.1 +/- 2.1 months. All patients had morphologic verification of the process. Distribution according to tumor localization was as follows: breast cancer--60 (71.4%), ovarian cancer--13 (15.5%), lung cancer--7 (8.3%), other localizations--4 (4.8%). Age varied from 22 to 73 years old. All patients had normal hematological status and survival expectation more than 3 months. Hematological complications were mentioned after the first cycle of chemotherapy in 70% cases.