Cancer immunotherapy: current opportunities and perspectives

Cancer immunotherapy is a relatively new and pro­mising method of treating neoplasms. Understanding the antigen-directed cytotoxicity of T-lymphocytes has become one of the central directions in involving the immune system in the fight against cancer. Basic research in this area has led to the invention of checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. Cytokines can enhance the action of T-lymphocytes for their ability to directly stimulate effector and stromal cells in tumor focus and enhance recognition of tumor cells by cytotoxic effector cells. They were the first in cancer immunotherapy and remain relevant to this day. Today, immunotherapy is an effective treatment for most malignant tumors, including melanoma, non-small cell lung cancer, liver, stomach, bladder, cervical cancer, some types of breast cancer, lymphoma, etc. However, immunotherapy of some malignant tumors is ineffective, therefore, the development of new and improvement of existing immunotherapy agents is actively underway, and there is a hope that the indications for its use will expand. For this purpose, this review discusses the principles of action of various classes of immunotherapeutic anticancer agents, namely cytokines, immune checkpoint inhibitors, and adaptive T-cell therapy. The work highlights their indications, efficacy and toxicity from the use of each class of drugs, as well as the prospects for the development of immunotherapeutic anticancer drugs.

Urothelial cancer: population-based analysis of the problem in Ukraine

The aim of this work was to conduct a population analysis on the basis of the National Cancer Registry with the primary goal: to determine the effectiveness of urothelial cancer treatment in Ukraine; and the secondary goal: to identify the main trends and approaches to therapy with an assessment of their impact on overall survival. Materials and methods. The design of the study was retrospective observational. The analysis was conducted based on the data of the National Cancer Registry from 2008 to 2020. A total of 12,698 patients with urothelial tumors of the upper urinary tract and bladder who underwent surgical treatment were analyzed. Statistical sampling was performed based on the creation of the most homogeneous groups of patients with bladder cancer (BC) and the upper urinary tract carcinoma (UUTc) who had the required number of notified parameters for further analysis. The primary objectives of the analysis were to determine: the average age of primary detection of the studied nosologies, level of detection depending on gender, frequency of diagnosis verification before surgery, extent of surgery, frequency of postoperative complications based on data on 30-day rehospitalization, the level of deviation of the principles for prophylactic medical patients’ examination from generally accepted recommendations. The secondary objective was to assess the cumulative survival of patients with urothelial tumors depending on the localization of the primary tumor and the type of surgery (organ-sparing or radical). Results. Organ-sparing treatment was more typical for BC, while radical treatment was performed in 15 % of patients with carcinomas. Organ-sparing treatment was more typical for UUTc (40 %). It should be noted that in this nosology it is accep­table for invasive forms of urothelial cancer. The level of 30-day hospita­lization was low in both pathologies, with a slightly greater advantage of UUTc. The level of complications is grade III according to the Clavien-Dindo classification, averaging 0.2 % for the entire pool of patients. For BC, the overall survival rates by stages were: I — 73 %, II — 49 %, III — 18 % and IV — 11 % (chi-square = 1,807.207; p = 0.000001). For UUTc, the levels of 5-year overall survival correspond to the literature data, but there is a significant negative tendency to decrease the latter after a ­10-year period for all stages (chi-square = 146.298; p = 0.000003). In Ukraine, organ-sparing treatment for UUTc was not inferior to radical nephroureterectomy in the context of 5-year survival (51.3 vs. 51 %; log-rank test). The obtained data testify in favor of the 15% advantage of the total survival of patients who underwent radical nephroureterectomy at the premises of the National Cancer Institute (high volume center), compared to other regions of Ukraine. Levels of 5- and ­10-year survival in both nosologies were characterized by a statistically non-significant advantage of UUTc over BC of 7 %. Conclusions. Superficial and locally advanced tumors are the most complex ones in the treatment of urothelial cancer of the bladder and upper urinary tract in Ukraine. Superficial tumors require the most radical surgeries and subsequent effective local treatment. Locally advanced tumors require a comprehensive approach to treatment, adequate systemic therapy influences the final indicators of overall survival. In cases of surgical resectability and preservation of renal function, UUTc requires organ-sparing treatment; this approach aims to increase creatinine clearance in patients before systemic chemotherapy and to reduce the likelihood of progression of comorbidities and associated mortality.

Neutropenia and management of cancer patients during the COVID-19 pandemic

The COVID-19 pandemic has significantly affected the management of patients with cancer. Due to the quarantine restrictions imposed to some extent around the world, it was necessary to modify treatment regimens by reducing the number of sessions of chemotherapy and radiation therapy, as well as by postponing surgery. The volume of cancer screening has also been reduced. All this, from our point of view, in the long run may not have a very positive effect on the course of treatment and prognosis of cancer. Therefore, doctors today are constantly faced with the task of maintaining the effectiveness of treatment of malignant neoplasms, on the one hand, and reducing the risk of coronavirus — on the other, because, according to many sources, cancer patients are at risk of adverse COVID-19 course. This is especially true for patients with chemotherapy-induced neutropenia. In this article we wanted to demonstrate the latest approaches to the management of cancer patients in this difficult period. We also considered the options for wider use of granulocyte colony-sti­mulating factors to prevent neutropenia in the COVID-19 era. It is still controversy about this in the medical scientific community. Unfortunately, the data available today are not enough to make unambiguous statements about a particular patient management, but by analyzing the large number of publications made during the pandemic year, as well as updated National Comprehensive Cancer Network guidelines, we were able to answer most of the questions that interest us.

Clinical significance of anticancer vaccines (literature review)

During the past few decades, the advances in cancer immunotherapy have revived interest in the potential use of vaccines for the malignant tumor treatment. Tumor-associated antigens, which are abnormally expressed by tumor cells, are of decisive importance in the development of anticancer vaccines. Through the stimulation of immunological memory, therapeutic anticancer vaccines can result in long-term remission or healing patients. Therapeutic anticancer vaccines due to the potential safety, specificity and duration of effect can become an alternative to or increase the effectiveness of existing immunotherapies. This article presents data on the tumor antigen structure, characteristics of anticancer vaccines and the results of studies on the clinical efficacy of anticancer vaccines.

Anticancer chemotherapy with high-dose methotrexate

The literature review is devoted to the use of high doses of methotrexate in oncology. There is a brief historical overview of the use of methotrexate for the treatment of malignant neoplasms; the main mechanism of its cytotoxic effect on tumor cells, the development of resistance to methotrexate, the main indications for the use of high doses of methotrexate and the main side effects of this treatment are considered. The review details the results of using high doses of methotrexate in the treatment of patients with osteosarcoma, non-Hodgkin’s lymphomas, located mainly in the central nervous system, and acute lymphoblastic leukemia.

Labeling as a method of routine monitoring of tumor response to therapy

Surgical treatment is still one of the main methods of complex therapy of breast cancer. Due to the widespread use of non-adjuvant antitumor treatment, the issue of routine tumor labeling is becoming increasingly important. The purpose of labeling is to improve the quality of tumor control after neoadjuvant therapy and adequate surgical treatment. In this literature review, we will consider the methods for labeling to visualize a tumor site.

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Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer (literature review)

Background. Breast cancer is the leading cancer type in women. Improvement in its management requires a continuous investigation of new tools for diagnosis and treatment. Biomarkers for breast cancer remain a field of great interest, despite existing knowledge. Extensive research recognizes the critical role played by tumor-infiltrating lymphocytes (TILs) in terms of prognosis and prediction, but much uncertainty still exists about the application of this biomarker in clinical practice. Thus, the purpose of this paper is to review recent researches about the role of TILs as a prognostic and predictive factor in the clinical management of breast cancer subtypes. Materials and methods. Eligible studies from Medline, Pubmed, Google Scholar (2010–2020) databases were analyzed and retrieved. Results. For primary tumors, a positive correlation was found between TILs and survival prognosis for HER2+ and TNBC subtypes, while for luminal subtypes it was a negative correlation. The predictive value of TILs in the neoadjuvant setting is established for HER2+, TNBC subtypes. In the case of using TILs as a predictive factor for HER2-targeted therapy, it remains a concern due to controversial data. For residual tumor, it is growing body of evidence about the positive correlation of TILs and prognosis for all subtypes, but data are limited. Conclusions. TILs were found to have prognostic and predictive value. However, due to the heterogeneity of breast cancer subtypes, TILs as a biomarker should be interpreted with caution. Further studies need to be carried out to determine the validity of making a clinical decision based on TILs count.

Optimal integration of CDK4/6 inhibitors for treatment of hormone receptor-positive metastatic breast cancer

The paper analyzes the effectiveness of a new class of medications — CDK4/6 cyclin-dependent kinases inhibitors and discover the mechanism of its action. The article describes the general results of studies on palbociclib, ribociclib and abemaciclib* for the first- and subsequent-line of the therapy of HR-positive/HER2-negative metastatic breast cancer. The profile of adverse events of approved CDK4/6 inhibitors are considered. The combination of CDK4/6 inhibitors with endocrine therapy was shown to have benefits in survival, potentiality to reduce hormone resistance and great perspectives to improve clinical results of hormone receptor-positive metastatic breast cancer.

The effect of vitamin D on the development and course of breast cancer (literature review)

Breast cancer is the most common cancer among the female population worldwide. The incidence of breast cancer is increasing every year. This requires the search for new trigger factors that can contribute to the onset and course of this disease. One of these factors is vitamin D, which is constantly deficient in most of the world’s population. This article provides a review of clinical studies over the last 15 years on the relationship between serum vitamin D concentration and breast cancer risk, prognostic factors, survival and treatment outcomes, and the effect of vitamin D receptor status on breast cancer. Studies have shown heterogeneity in research results that found the relationship between low vitamin D levels and breast cancer risk, prognostic factors and survival. There was no heterogeneity in studies showing an association between decreased vitamin D receptor status and worse prognosis. The situation was similar when studying the effect of vitamin D on impro­ving treatment outcomes. Despite conflicting research results, most studies show a correlation between vitamin D deficiency and breast cancer risk, prognostic factors, survival and treatment outcomes. Therefore, the selected vector of scientific researches is rational both from the point of view of eliminating the pandemic of vitamin D deficiency among the world’s population and preventing the spread of breast cancer.