Vol 26, No 7 (2019)

"Success is the ability to move from failure to failure without losing enthusiasm," or the lessons we have learned The principles of treatment for HR+ HER2-metastatic breast cancer (mBC) for a long period of time remained unchanged. Consistent use of various endocrinotherapy options provided a significant increase in overall and disease-free survival rates with maintaining a high quality of life. However, over time, patients has a progress of disease due to development of resistance to treatment. Evaluation of the causes and ways to overcome resistance to hormone therapy has led to the discovery of powerful new treatment options for patients with HR+ HER2-mBC. The cross-interaction of various signaling cascades in the cell as a result of acquired mutations of estrogen receptors play fundamental role in the development of resistance to endocrine therapy. The malfunction of the PI3K-mediated cascade is the most frequent disorder in breast cancer and is associated with resistance to endocrine therapy. Phosphatidyl-inositol-3 kinase (PI3K) as a key coordinator of cell growth and vital processes has been attracting the attention of scientists for many years. The current review presents the main provisions characterizing the clinical significance of the PIK3CA gene mutation encoding PI3K kinase: the prognostic and predictive role of the PIK3CA gene mutation (PIK3CA+) in all subtypes of breast cancer; and justifies the allocation of a special group of patients in need of therapy that suppresses the PI3K activity.

The neutrophil/lymphocyte ratio is a simple and informative prognostic biomarker in patients with malignant tumors. In this review, the role of neutrophils in oncological processes and the immunological basis of their interaction with lymphocytes in the development of T-lymphocyte anergy are discussed. Examples of the clinical use of this ratio as a predictive and prognostic marker, as well as its relationship with some other factors, are presented.

Background. Ramucirumab is the first anti-angiogenic targeted drug that improves survival as monotherapy or in combination with paclitaxel in a difficult population of patients with gastric cancer and of esophagogastric junction cancer after progression against the background of first-line therapy. Objective. Comparison of randomized clinical trial data and results obtained from real clinical practice. Methods. In the settings of the St. Petersburg City Clinical Oncology Dispensary, 24 cases of disseminated gastric cancer progressing on first-line therapy were prospectively analyzed. As a second-line treatment, ramutsirumab+paclitaxel regimen was administered. Results. During study, the following results were obtained: the duration of treatment with ramucruumab ranged from 2 to 16 months; median duration of treatment was 5 months, median overall survival - 18 months. Conclusion. The data obtained are comparable with the results of the randomized international registration RAINBOW study, which makes acceptable the use of this drug in real clinical practice.

Background. There is evidence that neoadjuvant chemotherapy (NACT) in some cases stimulates metastasis of breast cancer (BC), and the increased aggressiveness and metastasis of the tumor under the action of chemotherapy are associated with stimulation of tumor stem cells, the activity of which is determined by increased expression of stemness genes (SG). New tumor markers associated with a high risk of disease progression against the background of the treatment are required, and it has a greatest importance for patients receiving NACT in the preoperative period. Objective. Assessment of the immediate effectiveness of NACT and metastatic-free survival in patients with breast cancer depending on the presence of amplifications of regions of SG localization. in the primary breast tumor. Methods. Evaluation of the predictive and prognostic significance of the presence of amplifications of the SG loci 3q, 5p, 6p, 7q, 8q, 9p, 9q, 10p, 10q21.1, 12p, 13q, 16p, 18q, 19p in a breast tumor was carried out before treatment in 103 patients receiving NACT. Depending on the number of amplifications in the tumor, the patients were divided into two groups: with the presence of ≥2 amplifications in the tumor and with or without a single stemness gene amplification. SG amplification was determined using a high density CytoScanTM HD Array, Affymetrix (USA). Results. It has been established that SG amplifications in the primary tumor do not have predictive significance. The main result of the study was the identification of their prognostic significance. It was shown that the achievement of both complete and partial regression of neoplasm against NACT in breast cancer patients with ≥2 amplifications of any regions of SG localization in primary tumor tissue leads to a significant increase in metastatic-free survival (Log Rank [Mantel-Cox] p=0,025). At the same time, even a good response to NACT does not lead to an increase in the survival rate of patients with 0-1 amplification of SG. Conclusion. Thus, the results show that only patients with ≥2 SG amplifications have benefit from the treatment with NACT in terms of increasing survival, and these patients should receive NACT.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC with auto-HSCT) is the current standard for the treatment of primary refractory forms and the first recurrences of Hodgkin’s lymphoma (HL). HDC with auto-HSCT is effective for 50-60% of patients with the first late chemotherapy-sensitive recurrence of HL. Modern therapies for treating HL with high efficacy and low toxicity are particularly relevant for patients with HL who are not candidates for HDC with auto-HSCT, as well as for the occurrence of recurrent HL after HDC with auto-HSCT. Allogeneic hematopoietic stem cell transplantation (alloHSCT) can be performed in patients with recurrent HL after HDC with auto-HSCT with preserved chemo-sensitivity, preferably in young patients in a framework of prospective clinical studies. Brentuximab vedotin is registered for the treatment of patients with classical HL after failure (progression or early recurrence) of HDC with auto-HSCT or patients not candidates for HDC with auto-HSCT, if two or more chemotherapy lines fail, for consolidation after the HDC with auto-HSCT in patients with HL with a high risk of recurrence or progression, in first-line therapy with advanced stages of HL, most preferably for young patients, patients with a high risk of recurrence. In patients with HL recurrence, high activity of PD-1/PD-L1 checkpoint inhibitors that activate antitumor immunity (nivolumab, pembrolizumab) was noted. The therapeutic efficacy of PD-1/PD-L1 checkpoint inhibitors does not depend on the response to previous therapy regimens (primary refractoriness or refractoriness to brentuximab vedotin). Promising areas of HL therapy are associated with the further study of new tumor cell targets and their signaling pathways.

The article outlines the basic principles and forms of work of a medical psychologist in a multidisciplinary team as part of the rehabilitation of cancer patients. The available scientific literature reveals limited information about the role of the medical psychologist, the principles and methodological foundations of psychological rehabilitation as part of a comprehensive rehabilitation of a cancer patient. This article sheds light on the hierarchy and organization of psychological rehabilitation in the context of the biopsychosocial approach of the rehabilitation service.

Background. In Russia, as in the world as a whole, morbidity and mortality associated with skin melanoma are increasing annually. The presence of melanoma brain metastases (MBMs) is traditionally associated with a extremely unfavorable prognosis. Currently, various treatment options for metastatic melanoma are available, including targeted therapy (TT) with BRAF and MEK inhibitors. New approaches have significantly improved the results of treatment of metastatic melanoma, including in patients with MBMs. This article presents the experience of St. Petersburg City Clinical Oncology Dispensary in the treatment of patients with metastatic melanoma with activating BRAF mutation, including patients with MBMs. Objective. Analysis of the clinical results of targeted therapy for patients with disseminated melanoma. Evaluation of the effectiveness of this therapy in patients with the presence of MBMs. Methods. Since 2002, 44 patients diagnosed with disseminated melanoma of the skin have been under observation. MBMs were detected in 8 (18.2%) patients, 31 patients received a combination of BRAF and MEK inhibitors (dabrafenib and trametinib, vemurafenib and cobimeinib) in the framework of TT. 11 patients received monotherapy with BRAF inhibitor. Patients with MBMs were subjected to radiation therapy in addition to TT, two of them underwent surgical treatment of metastases. Results. In the entire patient population, progression of the process was recorded in 29 patients out of 44 (66%), among patients with MBMs - in 3 out of 8. The median progression-free survival (PFS) for all patients of all subgroups was 12 months, and the median overall survival S) - 17 months. 23 out of 44 (52.27%) patients are alive. In the group of patients with MBMs, the median PFS and OS were not achieved, and the mean PFS and OS were 16.90±3.19 and 20.31±2.86 months, respectively. Description of the clinical case. A clinical case of a patient with skin melanoma and MBM, whose life expectancy against the background of complex treatment (surgical treatment+stereotactic radiotherapy+TT) is 2.5 years, is presented. Discussion. Despite the emergence of many new opportunities in clinical practice, the treatment of patients with metastatic melanoma and metastases to the central nervous system remains an important problem of modern clinical oncology. It is necessary to develop new combined approaches to therapy aimed at improving the effectiveness of treatment and improving the quality of life of patients. Conclusion. The authors’ clinical experience clearly demonstrates that the use of an integrated approach in combination with TT for treating patients with melanoma and MBMs in real clinical practice allows increasing the PFS and OS of such patients, making it comparable to that in the absence of MBMs.

Background. Perivascular epithelioid cell tumors (PEComas) are extremely rare mesenchymal neoplasms that can affect almost any organ. Difficulties of diagnosis, lack of prognostic factors and adequate treatment reduce the overall survival of patients with this pathology. The article presents the latest achievements in the field of drug treatment of malignant PEComas. Description of the clinical case. An own clinical observation of successful application of everolimus in 40-year-old patient suffering from a malignant PEComa of the uterus with lung metastases is presented. Therapy lasts more than 7 months, the maximum effect of the treatment is stabilization of the process. Conclusion. Standard chemotherapy regimens are ineffective for PEComas and are accompanied by the rapid development of process progression. Analysis of the molecular mechanisms of the disease led to the emergence of a new class of drugs - mTOR inhibitors, currently the main method of drug treatment of this pathology. Nevertheless, the issue of choosing the second and subsequent lines of therapy has not been fully studied. However, timely and correct diagnosis determines a higher efficacy of the treatment and, therefore, improves the quality of life and life expectancy of this category of patients.