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No 7 (2024): Diagnostics and Oncotherapy (1)
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DIAGNOSTICS AND ONCOTHERAPY

7-12 767
Abstract

Adjuvant therapy with trastuzumab made a significant contribution to improving disease-free and overall survival rates in patients with HER2-positive breast cancer. However, in a number of clinical situations the risk of disease recurrence remains increased. Carrying out neoadjuvant treatment followed by post-neoadjuvant therapy, depending on the degree of pathomorphological response, is the modern standard, allowing to cure a significantly larger number of patients. This became possible thanks to the expansion of the arsenal of terget anti-Her drugs and the introduction into real clinical practice of double anti-HER2 blockade (trastuzumab + pertuzumab) and an antibody conjugate with a cytostatic drug – trastuzumab emtansine. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of HER2-positive breast cancer” was conducted. The survey involved 50 specialists from different regions of the country who are directly involved in developing a treatment plan for patients, which allows them to reflect the preferences of leading chemotherapists regarding tactics for HER2-positive breast cancer. This publication reflects the results of part of the survey, devoted to the choice of adjuvant and post-neoadjuvant therapy for HER2-positive breast cancer. Identified a clear positive trend in favor of neoadjuvant treatment followed by post-neoadjuvant therapy using modern targeted drugs such as pertuzumab and trastuzumab emtansine. The survey results show that 68% of patients with RCB-II–III residual tumor receive post-neoadjuvant trastuzumab emtanzine, in 2021 this figure was only 24%. The absolute majority of patients who have not received neoadjuvant therapy, but have N2–3 stage, receive double anti-HER2 therapy with trastuzumab + pertuzumab in the adjuvant setting. High adherence to the therapy was noted, as 97% of patients complete the planned course of T-DM1, and 91.2% of patients complete a year of adjuvant anti-HER2 therapy. These figures are noticeably higher than the indicators of registration studies. Issues of effectiveness come to the fore in choosing therapy. Issues of drug availability remain relevant, but are not decisive. The survey also revealed factors that were not obvious at first glance and influenced treatment results.

13-17 377
Abstract

Rationale. BRCA1 associated triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. At the same time, carcinomas that develop in carriers of BRCA1 mutations are characterized by extremely high sensitivity to DNA-damaging chemotherapy. Mitomycin C alone or in combination with platinum agents has already demonstrated promising results in the treatment of BRCA-associated ovarian cancer (OC) and metastatic breast cancer. In this article, we present the results of a retrospective study aimed at comparing standard neoadjuvant chemotherapy regimens (NACT) with mitomycin-based regimens for primary locally advanced BRCA1-associated TNBC.

The aim of the study is to determine the effectiveness of the combination of mitomycin and platinum compounds during neoadjuvant therapy in patients with primary locally advanced BRCA1 – associated TNBC.

Materials and methods. The study included 89 patients diagnosed with primary locally advanced BRCA1-associated TNBC. Patients were divided into three groups depending on the therapy: 1) 4 cycles of anthracycline and cyclophosphamide followed by 12 weekly injections of paclitaxel (n = 48) (AC + T), 2) 4 cycles of anthracycline and cyclophosphamide followed by 12 weekly injections of paclitaxel and carboplatin (n = 27) (AC + TCbP), 3) mitomycin C plus platinum followed by 12 weekly injections of paclitaxel (n = 14) (MR + T). Pathological complete response (pCR) rates were compared.

Results. The pCR rate in the MP+T group was 10/14 (71%). In patients with BRCA1-associated breast cancer who received AC + T and AC + TCbP regimens as NACT, the pCR rate was 17/48 (35%) and 19/27 (70%), respectively. The difference in pCR rate between mitomycin-containing therapy and the standard AC + T regimen was statistically significant (p = 0.03); the frequency of regressions was comparable to the frequency in the AC + TCbP group. During the 20-month follow-up period, no relapses were observed in the MR + T group. Relapses were more frequent in the AC + T group compared with the AC + TCbP group (16/48 (33%) vs 1/27 (4%), p = 0.003, Fisher’s exact test). The toxicity profile of the mitomycin-containing regimen included hematologic adverse events, the most common of which were anemia and leukopenia. Compared to standard regimens, nausea was significantly less pronounced. No patients reported alopecia with this regimen.

Conclusions. The addition of mitomycin C to neoadjuvant therapy for BRCA1-associated TNBC may be a promising treatment option for this category of patients and merits further study.

18-25 281
Abstract

Every year, 400,000 new cases of renal cell carcinoma (RCC) and 175,000 deaths are registered worldwide. Currently available advanced treatments for RCC have less toxicity than previously used therapeutic agents, but drug resistance remains a clinically significant problem. Drug resistance occurs as a result of angiogenic transition through activation of pathways that do not depend on VEGF targets of most first-line treatments. Lenvatinib with everolimus can fight resistance to increase both progression-free survival and overall survival in patients with metastatic RCC according to clinical studies.

26-33 223
Abstract

The indications for the use of checkpoint inhibitors in cancer diseases continue to expand in the coming years, which is a promising area for future clinical research. However, diagnosis of immune-related side effects is challenging due to its heterogeneous clinical manifestations, which range from subclinical to fulminant manifestations with high in-hospital mortality. A potential mechanism may be proliferation and clonal expansion of antigens by T-lymphocytes in tumor cells and affected self-tissues. The exact pathophysiological mechanism remains unclear and the risk profile of patients experiencing cardiotoxicity is unknown. Continued intensive efforts by the research communities and interdisciplinary collaborations in oncology and cardiology will help address these challenges and thereby allow immunotherapy to achieve its maximum potential benefit in the treatment of cancer

34-40 196
Abstract

Relevance. Malignant neoplasms of the thyroid gland account for 1–3% in the structure of oncological pathology in the territory of the Russian Federation. Fine needle aspiration biopsy of thyroid foci is an integral part of the examination and is included in both foreign and domestic recommendations. However, there is a problem of obtaining uninformative cytological conclusions, and the risk of obtaining false positive and false negative results remains.

Objective. To determine the possibilities of using vacuum aspiration fine needle biopsy under ultrasound control in patients with focal thyroid pathology in a multidisciplinary hospital.

Materials and methods. From 2021 to 2023, 331 patients with focal thyroid pathology were examined at the clinical base of the Department of Diagnostic and Minimally Invasive Technologies of the Clinical Hospital № 1 in Smolensk. All patients were divided into two clinical groups. Patients of both groups underwent a comprehensive examination, including palpation of the thyroid gland and lymph nodes of the neck, multiparametric ultrasound examination of the thyroid gland, including B – mode, color Doppler mapping, compression elastography, shear wave elastography, laboratory examination (calcitonin level, TSH, T3, T4, antibodies of TPO, AtTTP, thyroglobulin). In patients who had previously undergone surgical treatment, ultrasound was performed to determine areas of thyroid tissue, and additionally the level of thyroglobulin was determined as a marker of the recurrent process.

Results. The median size of the thyroid formation was 15.2 (13.9–19.1) mm. Mainly multiple foci of thyroid gland were detected in both the control group – 106 (79.1%) and the main 107 (54.3%) patients, the share of single foci accounted for 28 (20.9%) of the control and 90 (45.7%) of the main groups. Fine – needle aspiration biopsy was performed using the «Free hand» method using type syringe with a volume of 10 ml. During the vacuum fine – needle aspiration biopsy, depending on the data of the multiparametric ultrasound examination, the level of negative pressure in the range from –0.3 bar to –0.8 bar was determined. At a pressure of –0.3 bar, 54 (27.4%) were performed,–0.5 bar – 126 (64.0%),–0.8 bar – 17 (8.6%) vacuum fine – needle aspiration biopsy.

Conclusions. A device has been developed for the implementation of vacuum fine – needle aspiration biopsy with the creation of an improved technique for conducting vacuum fine – needle aspiration biopsy in focal thyroid pathology. The informative value of the method of routine fine – needle aspiration biopsy and vacuum fine – needle aspiration biopsy under ultrasound control in patients with focal thyroid pathology was evaluated. The sensitivity and specificity of fine – needle aspiration biopsy was 75.0% and 52.9%, respectively. The sensitivity and specificity of vacuum fine – needle aspiration biopsy during the study were 95.6% and 92.5%, respectively. The data obtained indicate the effectiveness of the method.

41-45 210
Abstract

Currently, special attention of researchers is attracted to the problem of diagnosing postoperative brain damage and cognitive impairment in patients with cardiovascular pathology after cardiac surgery without/under conditions of artificial circulation (AC). The main method of assessing the functional state of the brain is quantitative electroencephalography (EEG). Because of cardiovascular and oncological pathology could persist in one patient it is actual simultaneous cardial and oncological surgery under EEG monitoring.

Objective: based on the literature data, to find out the role of EEG in diagnosis of cerebral complications in patients with cardiovascular pathology after cardiac surgery without /under conditions of AC.

Methods. We found and analyzed data in specialized medical data base Pubmed, Scopus, Web of Science about EEG methods in patients after heart bypass with/without AC from 1980 to 2023 years.

Results. The quantitative EEG is very important for early diagnosis and prognosis for cerebral ischemia, epileptiform activity, postoperative cognitive dysfunction in patients with coronary heart disease (CHD) after coronary artery bypass with/without AC. However, the studies did not included patients with oncopathology, people over 70 years of age. It opens possibilities for early diagnosis of central nervous system functional condition in patients with lung cancer and cardiovascular disorders in simultaneous (concomitant heart and lung with/without AC) surgery. It will help a correction of complications in time and a development of guided rehabilitation

46-54 389
Abstract

Currently, tumour tissue biopsy to determine RAS/BRAF gene alterations, assess microsatellite instability status, and determine HER‑2/neu gene amplification/hyperexpression is the gold standard of diagnosis and allows the selection of optimal molecularly targeted therapy when considering treatment strategies for patients with metastatic colorectal cancer. However, biopsy does not fully reflect the existing intratumoural heterogeneity and clonal evolution of tumour cells, which can often be the cause of therapeutic failures. In recent years, liquid biopsy has attracted increasing attention as an additional and potentially alternative non-invasive tool for molecular tumour profiling. Assessment of circulating tumour DNA allows changes in the genetic status of the tumour to be monitored and the «burden» of disease to be measured dynamically in real time. Advances in liquid biopsy technology have led to promising new strategies for the management of patients with metastatic colorectal cancer in late-line therapy. The standard drug arsenal in this group of patients is limited to either repeat administration of previously effective therapy or regorafenib and the combination of trifluridine/tipiracil with bevacizumab, which are characterized by limited clinical activity. However, thanks to the discovery of the NeoRAS wild-type phenomenon and the rechallenge strategy of anti-EGFR monoclonal antibodies based on the study of clonal selection and evolution of tumour cells, the administration of epidermal growth factor inhibitors in a molecularly selected by liquid biopsy population is accompanied by good tolerability and efficacy. Numerous clinical studies are ongoing to further understand the mechanisms of tumour resistance and to develop new evidence-based treatment approaches in order to realise the concept of personalised medicine.

55-59 737
Abstract

Recently, the role of vitamin imbalance in carcinogenesis has been actively discussed. Studies aimed at assessing their role in the processes of cancer development are various, and the evaluation of the initial level of vitamins is relevant when planning antitumor therapy.

Objective. To determine the state of the initial level of B vitamins and homocysteine before chemotherapy in patients of different oncologic profile.

Material sand Methods. The level of vitamins B1, B6, B9, active form of B12* and homocysteine in fresh frozen plasma was determined by enzyme[1]linked immunosorbent assay (ELISA) using test systems in 66 patients with verified malignant neoplasms before chemotherapy. The study included 66 patients: women n=40 and men n=26, with cancer: gastric n=12, colorectal cancer n=21, cancer lung n=11, cancer pelvic organs n=22.

Results. According to the results of the study the increase in the level of holotranscobalamin (Holo-TC) and decrease in homocysteine in comparison with reference values was observed in 100% of cases. Significant difference was found only for B1: reliable differences between patients with colorectal cancer and with pelvic cancer (in the latter the mean value of B1 levels was 2.4 times higher at p = 0.0425). According to the results of correlation analysis, a weak correlation between B12 and B9 was determined. When comparing the levels of vitamin B12 and homocysteine in patients after surgical treatment and without it, no significant differences were found.

Conclusion. Increased Holo-TC levels and decreased homocysteine levels by ELISA are characteristic of all varieties of solid cancer, independent of sex, age, stage and previous surgical intervention. A relative decrease in vitamin B1 is characteristic of colorectal cancer

60-64 301
Abstract

We have presented a very interesting theoretical, practical and methodological clinical observation of a rare disease, extremely difficult for clinical and morphological diagnosis. A 35-year-old patient with gastric bleeding underwent emergency surgical treatment for a myofibroblastic tumor of the stomach, morphologically difficult to differentiate from gastrointestinal stromal tumors.



ISSN 2078-5631 (Print)
ISSN 2949-2807 (Online)