No 12 (2018)

Ovarian cancer (OC) is still the leading cause of death from oncogynecologic diseases. This article provides an up-to-date review of data on the incidence of a BRCA-associated OC. Various aspects of the treatment of patients with this disease, including features of chemotherapy for BRCA-associated OC, as well as the role and prospects for the development of new therapies, including targeted therapy and immunotherapy, are discussed. Information on the presence of BRCA1/2 gene mutations can have a significant impact on the treatment of patients with advanced OC at all stages of the treatment of patients. Further research in this area, including with the use of modern targeted and immunotherapeutic agents should contribute to the improvement of patient outcomes.

A new class of drugs - PD1 and CTLA4 blockers - is increasingly being used in real clinical practice. Along with this, data on cases of unexpectedly rapid growth of the tumor mass after the start of immunotherapy, which leads to a deterioration of the patient’s general condition, are accumulating. Acceleration of tumor growth by at least two times compared with the previously observed rate is called hyperprogression. Not all experts recognize the presence of this phenomenon; many specialists believe that accelerated tumor growth is a natural course of the tumor process. This article describes two clinical cases that meet the criteria for hyperprogression, and also presents a literature review, including a description of other clinical cases and potential immune and molecular genetic mechanisms that may underlie this phenomenon.

Immunotherapy with a PD-1 inhibitor (nivolumab) is highly effective in relapses and refractory forms of classical Hodgkin’s lymphoma (HL). In some cases, the use of this drug is considered the only possible treatment option for these patients with extremely unfavorable prognosis. The article describes the clinical observation of a female patient with relapses and a refractory course of HL, who underwent initiation of an early access program on the use of nivoluumab after 10 years of treatment of classical LH with various chemotherapy regimens, radiation therapy, and surgical treatment without a significant clinical and objective response. The treatment consisted of 40 nivoluumab injections, after which complete remission was achieved.

Background. At the stage of generalization of the tumor process, oncological patients need accompanying therapy, which, along with improving the quality of life, helps to reduce pain. These qualities, important for palliative therapy, are possessed by the domestic preparation hydrazine sulfate (HS), which has been used in our country for more than 20 years. Objective. Evaluation of the effect of long-term use of HS (Sehydrin) on the quality of life, severity of pain and the need for opioid analgesics for cancer patients receiving palliative care. Methods. The study was conducted in two research centers, and included 60 patients with malignant neoplasms (stage 3-4) with the presence of pain. HS was administered at a dose of 120-180 mg/day. The first course lasted for 28 days, followed by a break of 14 days, and the the second course of therapy was carried out for 28 days. Results. It has been established that the course treatment with HS contributes to increasing the effectiveness of anesthetic therapy for oncological palliative patients, and also at a certain stage reduces the need for tramadol in 51% of patients, improves certain indicators of quality of life, which is confirmed by positive evaluations of treatment satisfaction in 72% of patients. Conclusion. The best results with the use of HS (Sehydrin) were observed in patients who received small doses of opioids and lead a relatively active lifestyle.

Background. According to the world literature, a 5-year survival rate of 60-90% has been achieved with the use of chemotherapy for germ cell tumors (GCTs) among children. The prognosis depends on the histological variant, age, localization and prevalence of the tumor, and also on the initial level of the cancer-specific markers. Objective: to evaluate the survival rates of GCT patients under 18 years of age. Methods. Patients who were on treatment in the Department of Chemotherapy and Combined Treatment of Malignant Tumors in Children of the N.N. Petrov NMRCO from 1996 to 2017, were stratified into 3 groups (low, medium and high risk). In the Group 1 polychemotherapy was not performed; children in the Group 2 have received cytostatic treatment according to the VBP scheme; children in the Group 3 - according to the VIP scheme. 8 (11.1%) patients received therapeutic program according to the MAKEI-96 protocol. This program took into account the localization of the primary tumor, the stage of the pathological process, and the completeness of resection. The protocol offered PE and PEI schemes. The remaining patients were treated according to the following platinum-containing regimens: BEP, IGR, JEB, CADO, VAC. Results. The study included 72 patients (55 girls and 17 boys) under the age of 8 with extracranial localization of GCTs. Forty seven (65.3%) patients received therapy according to the principles of the TGM protocol. Complete remission was achieved in 59 (81.9%) patients. 14 (19.4%) children died. The mean follow-up period was 8 years (median, 5 years; IQR, 1 month to 21 years). The overall 5-year survival of GCT patients under the age of 18 years was 78.8±5%, recurrence-free survival - 76.8±5.6%, event-free survival - 61.6±5.8%, progression-free survival - 62.5±5.8%. Overall survival in the low-risk group was 100%, in the standard risk group - 92.8±3.7%, in the high-risk group - 55.1±10.1% (p=0.00097). There was significant difference in the recurrence-free survival and event-free survival rates in the standard and high-risk groups: recurrence-free survival in the standard risk group - 85.3±5.6%, in the high risk group - 53±13% (p=0.0097); event-free survival - 83.4±5.7 and 27.8±8.6%, respectively (p=0.0000). Conclusion. GCTs are the most curable oncological diseases in children. About 80% of patients with disseminated forms have a chance of recovery when using platinum-containing polychemotherapy regimens. The survival rates obtained in our study are comparable with the global ones.

The clinical manifestations of neuroendocrine tumors (NETs) are diverse and can mask other diseases, which leads to a delayed diagnosis and the progression of the disease. Carcinoid syndrome (CS) occurs most frequently and accompanies the development of approximately 20-35% of high-differentiated tumors of the jejunum or ileum, as well as NETs of other localizations. The main manifestations of CS include diarrhea, hot flashes, bronchospasm and carcinoid heart disease (CHD). Somatostatin analogues (SSAs) are the main systemic drugs for CS and CHD. SSAs should be prescribed even in the absence of clinical signs of CS when the biomarker threshold level is exceeded.

Venetoclax is a low-molecular selective inhibitor of the BCL-2 protein. The drug is highly effective in the treatment of various oncohematological diseases. The review presents the data of significant clinical studies on the efficacy and safety of venetoclax. Currently, randomized phase III trials are being conducted to evaluate combinations of VEN with various antitumor drugs for many diseases of the hematopoietic and lymphoid tissues, and perhaps after receiving the results, approaches to the treatment of these diseases will be changed.

Background. Pulmonary hemorrhage is one of the threatening complications of lung cancer. Patients often admit into general hospitals in urgent way with an advanced tumor process. These settigs largely determine the prognosis of the disease and the results of treatment. Description of the clinical case. A clinical observation of a 53-year-old patient is presented. This patient was treated in the Thoracic Department of the Thoraco-Abdominal Division of the N.N. Blokhin NMRCO with a diagnosis of central cancer of the right main stem bronchus, lower and middle lobe atelectasis, secondary obstructive pneumonia with abscess formation, recurrent pulmonary hemorrhage, pT3N2M0 (IIIA stage). The patient underwent emergency surgery for vital indications due to the recurrence of pulmonary hemorrhage. The total life expectancy was 32 months from the time of diagnosis. Conclusion. Correctly determined degree of pulmonary bleeding and the properly chosen surgical tactics in this severe category of patients is the best way of treatment, allowing not only to stop the bleeding, but also to simultaneously remove the tumor as the cause of bleeding, and maximize the patient’s life expectancy even with the palliative nature of the intervention. In addition, for some patients with advanced forms of non-small cell lung cancer (NSCLC), the removal of a tumor as a source of pulmonary hemorrhage allows to assign a chemotherapy in the postoperative period - an important component of the combined treatment of NSCLC [1].

Background. Lung cancer is the most common cause of death among oncology diseases in the Russian Federation and represents a serious social and economic problem. Until recently, for patients without activated mutations, standard chemotherapy (CT) was the only treatment option. The PD-1 receptor inhibitor pembrolizumab is the first drug that, in combination with HT, has shown efficacy in patients with advanced non-squamous NSCLC in the first line of therapy. Objective: to evaluate the cost-effectiveness of using pembrolizumab in combination with CT in the first line of conventional non-squamous NSCLC therapy in frame of Russian public health care system. Methods. The use of pembrolizumab in combination with platinum-based chemotherapy and pemetrexed was compared with platinum-based chemotherapy and pemetrexed therapy in the first line of common non-squamous NSCLC. The Markov model was developed to estimate the number of life years saved and direct medical costs for compared treatment regimens, based on data from the KEYNOTE-189 clinical study. Additionally, «cost/effectiveness» and «cost/utility» analyzes were performed. Results. 5-year general direct costs per patient on pembrolizumab with CT (7,06 million rubs.) is higher than the cost on CT (4,35 million rubs.). The «cost/effectiveness» ratio for a life year for therapy with pembrolizumab with CT is 2,67 million rubs., and 2,72 million rubs. for СТ. The «cost/utility» ratio for quality adjusted life year for pembrolizumab therapy with CTis 3,65 million rubs, and 3,96 million rubs. for CT. Conclusion. The use of pembrolizumab in combination with CT is economically feasible in the first line of therapy of common non-squamous NSCLC in the healthcare conditions of the Russian Federation.