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The off-label use of medicines is a routine clinical practice of oncology, especially in malignant-tumour patients with no treatment alternatives left when registered-drug options have been exhausted or standard therapies reveal contraindications. The recent shift from single-gene assays to multigene panels powered by full-exome or -genome sequencing expands the capacity of precision therapy, leading to a wider agnostic off-label use of targeted drugs for detecting a particular molecular genetic disorder. Studies of the off-label drug use in oncology will clarify the feasibility and safety of such prescriptions in patients with rare forms of malignancy when registered therapies have been exhausted or standard treatment reveals contraindications. This article examines the prevalence and landscape of off-label drug use in cancer patients and elaborates on the off-label principle. The paper presents a critical reflection on the off-label use of medicines in oncology.

The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months.

When we talk about hereditary ovarian cancer, we usually mean BRCA – associated cancer. Detection of hereditary ovarian cancer is important for the prevention of cancer in blood relatives of mutation carriers, and also makes it possible to use PARP inhibitors as maintenance therapy in BRCA – associated ovarian cancer.Due to the widespread introduction of modern molecular genetic technologies and the expansion of the diagnostic panel, mutations in genes other than BRCA 1/2 have begun to be detected in individuals with suspected hereditary ovarian cancer. Lynch’s syndrome is one of the most common and studied hereditary cancer syndromes. Interest in this syndrome in recent years is due to the emergence of the possibility of using checkpoint inhibitors – pembrolizumab and nivolumab for the treatment of colorectal cancer, stomach and endometrial cancer. To date, the definition of mutations in the genes of the MMR – system in ovarian cancer has not yet been applied in practice. Proband is a 69-year-old female with stage IIIC ovarian cancer at the time of diagnosis. The family history is burdened by 2 cases: lung cancer in the father and pancreatic cancer in the mother after the age of 60 years. Despite the advanced oncological process at the time of diagnosis, the start of combined treatment with 5 courses of neoadjuvant chemotherapy, incomplete cytoreduction, the patient’s overall survival during the follow-up period was 92 months. The clinical course of the disease was characterized as BRCA-associated ovarian cancer: long overall and relapse-free survival, long free-ofcharge interval with several relapses of more than 6 months; burdened family history; response to therapy with platinum and gemcitabine. However, when testing a patient with platinum-sensitive relapse by PCR, no mutations in the BRCA genes 1 and 2 were detected. To search for causal mutations, genetic testing was carried out using NGS technologies at the second stage. A germline mutation in the EPCAM gene involved in Lynch syndrome has been identified.

Descripton of metastatic HER2-positive breast cancer clinical case is introduced, multilineal strategy basing on clinical situation and disease features is justified, justification of the choice of anti-HER2 treatment in every line is made, in compliance with russian and foreigh oncology associations guidelines, along with comparance of rutine treatment results and randomised trials data.

Malignant tumors of the stomach and esophagogastric junction in advanced stages progress quite aggressively, and the prospects for treatment of these patients remain unpromising. The use of checkpoint-inhibitors has proven to be an advanced treatment method for various types of cancer around the world. In theRussian Federation, nivolumab has been successfully registered as a monotherapy for common or recurrent stomach or esophagogastric junction cancer after two or more lines of systemic antitumor drug therapy. This literature review focuses on the use of registered checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab) as mono- and/or combined therapy in tumors of the stomach and esophagogastric junction, including tumors with high microsat- ellite instability (MSI-high). This review includes a description of the main therapeutic approaches using checkpoint inhibitors: prescription in mono-mode, in combination with other checkpoint inhibitors (ipilimumab) and cytotoxic drugs, and in combination with tyrosine kinase inhibitors (regorafenib). Issues of efficiency and tolerability of these combinations in patients in different therapeutic lines are considered. The role of possible predictors of therapy response is analyzed: biomarkers such as PD-Ll, MSI, dMMR and TMB expression in tumor tissues as well as immunofenotyping in fresh biopsy samples are evaluated. This article reviews and evaluates the strengths and weaknesses of checkpoint inhibitors and their possible uses.

Introduction. Myocardial lymphoma is one of the rarest lesion localizations among all the lymphoproliferative diseases. Regardless of the current lack of generally accepted specific recommendations for the treatment of primary and secondary myocardial lymphomas the chemotherapy is carried out in accordance with clinical guidelines for the treatment of lymphoproliferative diseases, which in some cases results in a successful outcome.Materials and methods. The article presents a clinical example of the diagnostic procedure and treatment of a 65-year-old female with the following diagnosis: non-Hodgkin’s lymphoma st. II BE gr. II with the involvement of myocardium, cervical and mediastinal lymph nodes, and the right palatine tonsil. The patient received six courses of R-CEOP chemotherapy.Results and discussion. An echo-positive structure 28mm by 20 mm in size attached to the interatrial septum was found inside the right atrium following the second course of chemotherapy. Ejection fraction: 61%. Effect: regression exceeding 50%. Four months following the completion of treatment the ejection fraction was 63%, regression – exceeding 80%, thus implying a partial response.Conclusion. The diagnosis of lymphoma with a lesion in the myocardium has been positively verified by histology and IHC. Currently less invasive techniques are normally preferred, transesophageal cardiac echo guided biopsy being one. Similar to any other lymphoproliferative disease, myocardial lymphoma is a chemosensitive tumour that responds well to treatment. In each individual case, the treatment strategy must be patient-specific and take into account the somatic status of the patient, the tumour size and the degree of its spread, the tumour morphological type, and whether it would be possible to arrange adequate specialized support needed.

The tyrosine kinase inhibitors (TKIs) of the epidermal receptor growth factor (EGFR) such as gefitinib, erlotinib and afatinib, are the standard first-line therapy in locally advanced and metastatic non-small cell lung cancer (NSCLC) with frequent mutations of the EGFR gene. These drugs are more effective from the point of view of frequency response (FR) and survival without progression (SWP), less toxic and better tolerated than the standard two-component chemotherapy based on platinum drugs. The most frequent adverse events (AE) are gastrointestinal (GI) (diarrhea and stomatitis/mucositis) and dermatological (rash, dry skin and paronychia). They are usually mild, but in some cases symptoms can be moderate and more severity and have a negative impact on quality of life (QOL) of the patient and can require dose adjustment or discontinuation of treatment. Management of AEs, including preventive measures, supportive therapy, temporary cancellation and a reduction in the dose of the drug is important. Recommendations for the prevention and treatment of dermatological toxicity (rash, dry skin and paronychia) and toxicity for the gastrointestinal tract (diarrhoea, stomatitis and mucositis) related to therapy TKI-EGFR are developed. These guidelines describe in detail supportive therapy, the temporary discontinuation of the treatment and reducing the dose of the drug for KTI-EGFR.

The results of clinical and experimental studies of the effectiveness of radiotherapy in combination with cisplatin and Ftorafur in the comparative analysis with radiation therapy, radiation therapy in kombintsii with fluorouracil and cisplatin. Preliminary studies indicate that radiation therapy in combination with cisplatin and ftorafur affect longer diseasefree period. The question of chemoradiation therapy for cervical cancer remains open, and the results of the study indicate the need for further studies using chemoradiation radiomodifying derivatives fluoropyrimidines series.

This article analyzes the possibility of practical application of the most-studied molecular biological markers in the diagnosis and treatment of cancer. The possibilities of the use of genetic markers for the diagnosis of hereditary preventive caused tumors, for the early detection of cancer, targeted therapy for the selection, monitoring and prognosis of the disease. We proposed the universal algorithm for the study of molecular biological markers. The feasibility of the introduction of molecular biological research in laboratory of Clinical Oncology Dispensary of the Republic of Bashkortostan has examined.

A clinical case of trastuzumab emtansine in therapy line 4 in patient with metastatic HER2positive breast cancer is provided. After 10 courses of targeted therapy by the drug a complete response to the therapy was obtained. By results of PET CT conducted in the period from December 2015 to September 2017 the complete response is preserved.

Breast cancer in men is 100 times less common than in women. The principles of treatment of breast cancer in men are still based on knowledge obtained during the treatment of women with a similar pathology. The article reviews 67 cases of all breast cancer stages in men. The majority (50.7%) of all patients who initiated therapy had stage III-IV tumors. In most cases, the patients had an infiltrating ductal carcinoma (52.2%). The combination and complex treatment methods accounted for 53.6% of all cases. The radical mastectomy (89.6%) was the most frequent method of operative intervention. 29 patients (43.3%) received preoperative chemotherapy. 36 patients received adjuvant treatment. The adjuvant treatment comprised chemotherapy (29 patients), and subsequently was supplemented with antihormonal therapy in patients with receptor-positive tumors. The anthracycline-containing chemotherapy was the most prevalent among treatment regimens (72.4%). In 7 patients with a locally diffused process, the treatment was supplemented with radiotherapy. 72.2% of patients had a clinically significant estrogen receptor (RE) expression in the tumor and 61% of patients had a progesterone receptor (RP) expression. 85.0% of patients with stages I-IIA breast cancers showed the relatively high 5-year survival rates, and 67.5% of patients with stage IIB cancers showed 5-year survival. The survival rates for stages III and IV cancer were 18.1% and 16.6%, respectively.