[EXPERIENCE IN ORGANIZING THE WORK OF THE CENTER FOR PERSONALIZED TREATMENT OF MALIGNANT NEOPLASMS (NETHERLANDS)].

INTRODUCTION: In the last decade, there has been a «breakthrough¼ development of scientific approaches to the assay of genomic and immune factors underlying anti-cancer treatment efficiency. The choice of antitumor therapy in practice is increasingly determined by molecular signatures, and not only by the specificity of organ tumor originated from (or by the histological properties of the tumor). An urgent and important scientific and practical task is to study the successful experience of organizing Centers for Personalized Cancer Treatment (CPCT). AIM: analysis of the 10-year experience of the Clinical Center for Personalized Cancer Treatment in the Netherlands. MATERIALS AND METHODS: Data were extracted from the internet databases using keywords: personalized cancer therapy / treatment, cancer, targeted therapy etc.Results. The Center's research project collects data on patients with metastatic cancer who are eligible for anticancer treatment as part of standard practice. The system accumulates various information about tumor DNA, mutations and abnormalities in DNA, treatment results (outcomes), as well as other important clinical characteristics, including individual tumor process. Registered parameters are stored in a digital database and are available for scientific research. DISCUSSION AND CONCLUSIONS: CPCT consider the possibilities for the more in-depth genomic analysis of patient DNA (including non-tumor DNA) in the future in order to improve the medical decision making regarding early diagnosis and personalized choice of anticancer therapies. Rapid progress will lead to the emergence of more advanced methods for re-evaluating biological samples accumulated in biobanks, that will facilitate the understanding the pillars of personalized anti-cancer treatment approaches as well as create an additional bases for the new drug development.

[QUANTITATIVE AND QUALITATIVE CHARACTERISTICS OF THE POPULATION OF PATIENTS WITH LIVER CIRRHOSIS IN MOSCOW].

INTRODUCTION: Liver cirrhosis is a major but preventable cause of health loss worldwide. The era of «big data¼ allows us to evaluate this nosology in a new format. PURPOSE: Evaluation of the registered population of patients with cirrhosis of the liver of cirrhosis of various etiology in Moscow. Moscow. MATERIALS AND METHODS: Based on the data of the Moscow Department of Healthcare for the drug provision for the period from 2017 to 2019. Тhe population of patients with an established diagnosis of liver (other etiology) was characterized according to ICD-10 code K.74 (K74.0-74.6) according to the International Statistical Classification of Diseases and Related Health Problems of the 10th revision. RESULTS: Over a 4-year period, more than 2 thousand patients with established diagnosis of liver cirrhosis received preferential drug provision in Moscow. The largest part of the population of patients with liver cirrhosis receiving preferential drug provision in Moscow is represented by the patients of age groups 40-59 years old and 60-79 years old, the groups 30-39 years old and 80-99 years old were comparable annually. There was a decrease in the number of patients with liver cirrhosis in the age groups of 30-39 and 18-19 years compared with the base year (2017) by 37% and 57%, respectively. At the same time, in pediatric patients (from the neonatal period to 17 years), there was an intensive increase in patients from 52 to 550% compared to the baseline year (2017).

[THE QUALITY INDICATORS TO ASSESS THE PROSTATE CANCER RADIOTHERAPY PERFORMANCE (BRIEF REVIEW)].

INTRODUCTION: The radiation therapy (RT) plays a tremendous role in the consistent treatment of prostate cancer (PCa). The research ideas underpinning the wide implementation of innovative digitalized continuous (nonstop) dynamic auditing are coming true. Simultaneously, there are increasing challenges in selection of RT quality indicators. OBJECTIVE: to study the pivotal indicators for RT quality assurance in treatment of PCa and to highlight the breaking through developments securing the delivery of top-quality cancer care in radiation oncology units. MATERIALS AND METHODS: The literature search was performed in the PubMed database and the Google system. The inquiries included such terms as: "quality of care", "quality assessment criteria", "indicators", "prostate cancer" and "radiation therapy". A logical and semantic approaches were applicated to select the relevant scientific resources. RESULTS: In most relevant studies, the variations of the Delphi technique are used to choose the quality assessment criteria. The targeted research papers describe the development of QIs for assessing the quality of radiation therapy in patients with locally advanced PCa; a hierarchical list of QIs has been generated. The adequate registration of information has huge impact on quality assessment to draw the definitive thorough conclusions. DISCUSSION: The further improvement of Delphi technique may form one of pillars for the development of valuable RT quality measures. Considering the math aspects and the physical nature of RT, it seems being important to include the key opinion leaders in the field of clinical oncoinformatics, radiation informatics, and specialists from technical industries in the expert committees for the selection of RT QIs.

[History of aminoquinoline preparations: from cinchona bark to chloroquine and hydroxychloroquinon].

The article presents a review of the historical facts related to the discovery and introduction of chloroquine and hydroxychloroquine. The history of studying aminoquinoline preparations is associated with the discovery of the antimalarial action of the bark of the quinine tree, the isolation of quinine from other active substances - alkaloids and the determination of their structure. The structural similarity of quinine and one of the first chemically synthesized dyes - methylene blue-was an important factor at the beginning of the synthesis of molecules with antimalarial activity in the 1930s in Germany. Pamaquin (plasmoquin, plasmoсid), quinacrine (quinacrine, Atebrin, Mepacrine), sontoquine (sontochin), chloroquine, primaquine, hydroxychloroquine, and mefloquine (Lariam) were consistently introduced in medical practice. Many of these medications are no longer widely used. However, chloroquine and hydroxychloroquine have not lost their relevance. The scope of their use has been expanded.

[ASSESSMENT OF THE ECONOMIC EFFICIENCY OF THE DRUG SUPPLY STRATEGY FOR PATIENTS WITH HEPATITIS C IN THE CITY OF MOSCOW].

Evaluate the cost-effectiveness of various options for the supply of direct antiviral agents for patients with chronic viral hepatitis C. An analysis of the data of Moscow Department of Health on the drug supply of patients with chronic hepatitis C antiviral drugs at the expense of budgetary funds in Moscow was carried out. The direct medical costs of the urban healthcare system for the use of direct antiviral action drugs for the period from 2017 to 2019 were calculated. For the period from 2017 to 2019, 6,936 patients with chronic hepatitis C received medication with antiviral drugs at the expense of budget funds in Moscow. An increase in the number of patients compared to the base (2017) year was noted by 76%, as well as an increase in the volume of interferon-free antiviral therapy sets against the background of an increase in budget expenditures by 212%. The average level of cost for all sets with direct antiviral drugs amounted to 689,844 rub. The most commonly used set is Dac + Asu. The average cost of this set per patient treated as part of the first-line antiviral therapy was 58,899 rub. cheaper than a set of 3D, and 58,861 rub. more expensive than the Grz/Elb set, while the need for retreatment for the Dac + Asu set was 8.4%, and for the 3D, Grz/Elb and Gle/Pib sets, 0.58%, 0% and 0%, respectively. An even greater excess of the average was recorded for the Sof + Dac, Sof + Sim sets: which naturally entailed the excess of the costs of treating one patient with this distribution of treatment sets and financial resources by 253,236 rub. and 189,173 rub., respectively, which is 1.36 and 1, 27 times the average cost of all prices for antiviral treatment sets. Most often, re-medication was provided to patients who were initially provided with Sof set (33%), followed by Sim + Dac set (18.6%), 8.4% of re-medication cases were registered in patients who received Dac + Asu set as the first line of therapy. Budget costs for the second and subsequent sets of therapy increased by 92,739,115.30 rub.

[Comparative characteristics of types of medical technologies assessment].

This article presents the results obtained during the analysis of different types of health technology assessment (HTA). In the world HTA agencies can be organized at the national (federal), regional or local levels; they can have various levels of dependence on public authorities (independent, public, dependent), various sources of financing (state, mixed). The nature of the tasks and the range of powers of the institutions for HTA differ: regulatory, organizational or advisory. They themselves can initiate HTA (proactive), or they can conduct HTA at the suggestion of the applicants and analyze the quality of the HTA reports provided (reactively). HTA can be focused on economic assessment, comparative clinical assessment, as well as balanced, both on economic and comparative clinical assessments. HTA may be conducted on drugs, medical devices, and other medical technologies. The methods for conducting HTA significantly depend on its subject. In terms of the scope of the assessment, it is possible to single out full OMT, mini-OMT and express-OMT, as well as fast-track-OMT, proposed by the HTA agency in the UK. The final users of HTA (administration, suppliers, patients) and its perceptions (instrumental, conceptual, or formal) are specified. The impact of HTA on decision-making is progressively increasing, as the number of medical technologies that should be assessed to maintain budget discipline is increasing. The versatility of HTA indicates its universality and can contribute to the further expansion of its application at various levels of medical care around the world.

[Dynamics of LINE-1 Retrotransposon Methylation Levels in Circulating DNA from Lung Cancer Patients Undergoing Antitumor Therapy].

Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.