DIAGNOSTICS AND ONCOTHERAPY
Cyclin-dependent kinase 4/6 inhibitors (iCDK4/6) are the generally accepted standard of care for the treatment of luminal HER2-negative metastatic breast cancer (ER+HER2- mBC). Data from randomized and observational studies have proven the high effectiveness of the combination of iCDK4/6 and endocrine therapy (ET) both in the 1st and in subsequent lines. The use of new drugs in real clinical practice is determined by a number of factors, including the awareness of doctors, their personal experience and subjective preferences, as well as financial support and availability in a particular region. To assess the frequency of prescription of CDK4/6, as well as other types of treatment in the 1st‑2nd line of therapy for ER+ HER2- mBC in real clinical practice in Russia, as well as to determine the factors and preferences of doctors influencing their choice, the National Association of Oncomammologists (NAOM) conducted a survey “Prometheus” of oncology specialists. From February 15 to August 30, 2023, a web survey of healthcare professionals who treat patients with mBC was conducted on the website anketolog.ru. An invitation to survey was sent out through the NAOM database, 112 questionnaires were received and processed. Earlier, in 2020, the “Prometheus” survey was conducted on the territory of the Russian Federation for a similar purpose. In this paper, we present the results of an updated and expanded survey and evaluate changes that have occurred over the past 3 years in actual clinical practice. The results of a 2023 survey conducted in the Russian Federation on the choice of early-line therapy for ER+HER2- mBC showed that, compared with the 2020 survey, the level of “trust” in iCDK4/6 has increased among practicing physicians, and the indications for their use have expanded, including visceral metastases (and even pending visceral crisis), the indications for prescribing chemotherapy in the 1st line have narrowed. When using monoET in the 1st line, the majority of respondents prescribe iCDK4/6 in the 2nd line. Obviously, the wider use of iCDK4/6 is associated not only with the accumulation of clinical knowledge and experience in the use of drugs, but also with improved drug supply. However, the main limitations to the use of iCDK4/6 are still insufficient funding and organizational difficulties. However, it should be noted that 1/5 of the respondents do not face any restrictions and widely prescribe combination therapy.
Inflammatory processes in the mammary gland (MG) do not lose their relevance, the frequency of occurrence reaches 16% among all diseases of the MG. Non-lactational mastitis (NM) – inflammation in the MG outside the period of pregnancy and lactation – stands out among them [1]. With untimely and non-radical treatment of acute forms, there is a transition to chronic, with the formation of bacterial biofilm in the focus of inflammation and thick scar capsule after repeated surgical interventions, which is due to a vicious circle. The clinical picture of non-lactational chronic mastitis in most cases resembles a diffuse (mastitis-like, edematous-infiltrative) form of breast cancer (BC), which determines the differential-diagnostic difficulties in referring to a doctor both at initial treatment and at recurrence. This problem is faced by doctors of different specialties: oncologists, surgeons, gynecologists, therapists, specialists in radiation and radiological diagnostics [2, 3]. Radiation diagnostics is always the «gold standard» in the diagnosis of breast diseases, but has a number of disadvantages in the inflammatory process in the breast, and, in some cases, it is worth prioritizing the ultrasound method of investigation [4]. Through the combined interpretation of clinical data and ultrasound (USG) findings, the following parameters should be evaluated: skin thickness, pre-mammary fatty tissue, structure of glandular parenchyma of the MJ, presence and boundaries of inflammatory infiltrate/infiltrates in the MJ tissue; formation of «rarefaction» zones, microabscesses and/or already formed «draining» abscess cavities, assess the content of fluid cavities (homogeneity/homogeneity), the presence of pyogenic capsule, as well as the boundaries of inflammation/abscessing with unchanged breast tissue, taking into account possible «microfoci» outside the main mass of changes (like «satellites», «fluid spurs»). It is important to analyze the state of the ductal system of the breast (ductal diameter dilation, intraluminal content) and possible connection of ducts with abscessed areas, which may be a predictor of further spread of the process, recurrence or chronicization of the disease. Inflammation on the background of subacute and chronic process can lead to the development of fistulas [5]. However, there is not always the classic ultrasound picture of a purulent focus in the breast [6–9].
Purpose of the study. To identify the most informative combinations of small non-coding RNA molecules (miRNA) associated with malignant tumors of the thyroid gland (TG) in patients with nodular formations with an uncertain conclusion based on fine needle aspiration biopsy (FNA) and the absence of gene mutations.
Materials and methods. The study included 83 patients with thyroid nodules according to the results of ultrasound examination with an indefinite cytological conclusion based on FAB materials (category III–V according to the Bethesda classification) and the absence of V600E mutations in the BRAF gene, NRAS, HRAS, KRAS genes in the molecular genetic study of the aspirate. Expression activity of miRNA was determined by realtime PCR in aspirate. Using cluster analysis, homogeneous groups of miRNAs associated with malignant thyroid lesions in patients were identified.
Results. In the cells of thyroid nodules obtained during FNA, malignant lesions are associated with an increase in the expression activity of miRNA‑146b,–221,–222,–885–5p and a decrease in the expression of miRNA‑455–3p and miRNA‑574–3p. Reciprocal changes in expression activity in pairs miRNA‑146b/miRNA‑574–3p, miRNA‑221/miRNA‑455–3p, miRNA‑222/miRNA‑574–3p, miRNA‑885–5p/miRNA‑574–3p are more informative when differential diagnosis of benign and malignant thyroid formations than assessing the expression of individual miRNAs.
Conclusion. With an uncertain cytological conclusion based on the FAB data of thyroid nodules (categories III–V according to the Bethesda classification) and negative results of a molecular genetic study regarding gene mutations, it is recommended to direct further diagnostic search in determining the expression in the aspirate of miRNA‑146b,–221,–222,–885–5p,–455–3p,–574–3p.
Over the 20 years of the study period in Ugra there has been an increase in the standardized lung cancer incidence rate for 20 years of the study period in Ugra there is an increase in the standardized lung cancer incidence rate. The risk of lung cancer development is closely related to environmental factors, the main of which are: tobacco smoking and air pollution with carcinogens. We studied average annual concentrations of atmospheric air pollutants and standardized incidence rates of lung cancer in men and women in the territories of the county. As a result of cross-correlation analysis it was obtained that delayed correlation of lung cancer morbidity and average annual concentrations of formaldehyde in atmospheric air in men and women is manifested after 10–16 years of exposure; phenol after 13–17 years after exposure; nitrogen dioxide after 14–15 years after exposure
Proton pump inhibitors (PPIs) are the undisputed leaders in the treatment of acid-related diseases. In actual clinical practice, the use of PPIs has been growing exponentially in recent decades. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines and reviews and meta-analyses of the current decade on the safety of PPI use note that when prescribing PPIs in large doses for a long period, the possibility of developing numerous side effects should be taken into account. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to 12/01/2023. The review addresses issues of drug interactions between PPIs and chemotherapeutic drugs, which should certainly be taken into account in real clinical practice. In addition, recent reviews and meta-analyses have examined side effects of long-term PPI use, such as increased risk of infection (Clostridium difficile infection, community-acquired pneumonia), electrolyte disturbances, kidney damage, increased risk of hip, wrist and spine fractures; increased cardiovascular risk and a number of others, which can also have an adverse effect on the prognosis of cancer patients. The risk of developing gastric cancer with long-term PPI therapy can be considered as a likely side effect, since their association with PPI use is not denied or questioned in recent reviews and meta-analyses. There is still uncertainty regarding the increased risk of other cancers, since there are publications that do not confirm their association with PPI use. However, the presented review, despite a number of contradictions, allows us to conclude that the increased cancer risk with long-term use of PPIs is real and must be taken into account when prescribing PPIs for a long term.
Extragastrointestinal stromal tumors (EGIST) are rare lesions in the mesenchymal neoplasm, accounting for less than 1% of the primary neoplasias of the digestive tract. In only 10% of the cases EGIST may affect any segment of the gastrointestinal tract and can occur in other locations (omentum, mesentery, or retroperitoneum, GIST arising from the pancreas). The incidence is approximately 14.5 patients per 1 million persons [1–3]. To date, more than 190 cases have been published. We reported a rare case of huge mesenteric extra-gastrointestinal stromal tumor presenting as a peritoneal mass in a 53-year-old patient
Given the poor treatment outcomes of disseminated gastric cancer (dGC), the search for new drug treatment options remains a pressing issue. According to some literature, the use of a chemotherapeutic triplet in the first line improves patient survival rates. An interim analysis of a prospective randomised phase III trial examines the comparison of the chemotherapeutic regimens mFOLFIRINOX and mFOLFOX6 in the first-line treatment of HER2-negative gastric adenocarcinoma. In this interim analysis, significant differences between patients receiving mFOLFIRINOX or mFOLFOX6 regarding the primary endpoint of mVBP were detected only in the group of patients with dissemination to the retroperitoneal lymph nodes. Overall, based on the results of this work, it can be concluded that the majority of patients do not require intensification of first-line treatment for gastric adenocarcinoma in the form of mFOLFIRINOX chemotherapy. However, final conclusions on the efficacy of the triple combination can only be drawn upon completion of the entire study.
The overall incidence of liver cancer in the Republic of North Ossetia-Alania has remained stable over the past five years. Moreover, the initial diagnostic of HCC occurs at widespread stage, which limits the possibilities of cured therapy. The Republican Oncology Clinic has accumulated experience in using the drug lenvatinib for advanced and metastatic hepatocellular cancer. In the realities of a small regional dispensary, and has to find a balance between efficiency and availability of therapeutic options to provide effective therapy for all patients. The authors conducted a single-center retrospective analysis of the effectiveness and safety of lenvatinib in real clinical practice in patients with hepatocellular cancer at the Republican Oncology Center of the Republic of North Ossetia Alania. The analysis included 18 patients with HCC who received lenvatinib monotherapy. 11(61%) patients had concomitant viral hepatitis B or C, 15 (83%) had distant metastases to the lymph nodes, lungs, adrenal glands or other organs. A feature of this patient population is the long period of time from the prescription of drug therapy for HCC to its actual start – on average 46 days, with a range from 5 to 100 days. We believe that a delay in initiating therapy may affect the results obtained. Median PFS in 1st line of lenvatinib therapy was 10.1 months (2.3 months to 13.1 months). Median PFS2 (defined as the time from 1st line treatment on lenvatinib to progression on first subsequent therapy) was 19.1 months. 6 (33%) patients received lenvatinib in the second line after progression on another drug therapy. The median second-line PFS in this case was 5.9 months (3.8 months‑7.7 months). Lenvatinib had a manageable and predictable tolerability profile. No new safety signals were identified.
Conclusion: The use of lenvatinib as monotherapy in adult patients with advanced or unresectable hepatocellular carcinoma has proven to be an effective strategy that balances clinical benefit and availability of the drug.
Abemaciclib is an oral inhibitor 4 and 6 (CDK4/6). Abemaciclib differs from other drugs in this group in suppression spectrum of cyclin-dependent kinases and is proven to improve survival rates in different treatment lines of metastatic breast cancer. In randomized clinical trials 3rd phase in patients with early hormone-dependent HR+ HER2 negative breast cancer high risk of progression abemaciclib in conjunction with hormone therapy significantly improves invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS). Long- term outcome studies monarchE with 5 – year follow – up of patients showed that abemaciclib adding to ET increases 5-year IDFS from 76 to 83.6% (HR0.680; 95% CI 0.599 to 0.772; p <0.001) and 5-year DRFS from 79.2% to 86.0% (HR0.675; 95% CI 0.588 to 0.774; p <0.001). Adverse events of 3rd degree and higher are registrated in 45.5% of patients in abemaciclib group and in 12,7% in control group and mainly presented by neutropenia (18.6 and 0.7%) and diarrhea (7,6 and 0.1%). Toxicity profile was expected and controlled. The reasonable dose reduction of abemaciclib did not lead to deterioration of long-term treatment result.
ISSN 2949-2807 (Online)