В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Introduction. mBRAF mCRC has the aggressive phenotype. The incidence of such mutation in Europe and the USA is around 8–14%, in Asian countries – 4–8%. The purpose of this population-based study was to determine the incidence and identifying prognostic factors in pts with mBRAF mCRC in Russia. Materials and methods. A multicenter retrospective analysis of clinical data and treatment results of pts with mBRAF mCRC was performed. The main method for determining mutations was a PCR. The main efficacy endpoint was progression free survival (PFS) at the 1 st line. Multivariate analysis was performed using Cox regression model. Results and discussion. 437 out of 8648 pts (5.17%) with a known mutational status had mBRAF (V600). Clinical data were collected from 131/437 (30%): the right-sided primary tumor – in 58,6%, left-sided – in 19%, rectum – in 21,4%. ORR in pts with mBRAF was 31%, median PFS was 6 months. We didn’t revealed any differences between FOLFOXIRI and doublets (XELOX/ FOLFOX or XELIRI/FOLFIRI) in terms of PFS (HR 0.9, 95% CI 0.49–1.52, р = 0.6) and OS (HR 1.5, 95% CI 0.61–4.1, р = 0.35) in pts with mBRAF. Conclusions . The incidence of mBRAF gene in the population of pts with mCRC in the Russia is low and we found a high incidence of localization of the primary tumor in the rectum. We didn’t reveal any differences between the usual duplets and standard regimen for such mutation - FOLFOXIRI in term of 1 st line PFS.

Objective: to identify factors associated with efficacy of an aflibercept-chemotherapy combination in patients with metastatic colon cancer. Materials and methods. This retrospective multicenter study was conducted in 20 clinics from 15 regions of the Russian Federation. The main efficacy outcome was progression-free survival (PFS). We performed univariate and multivariate analysis to assess the impact of various factors of PFS. Results. Two hundred and fifty-seven patients received aflibercept-containing chemotherapy; of them, 175 participants (68.1 %) received it as a second-line therapy. The objective response rate and median PFS were 18.7% and 5 months (95% confidence interval (CI) 4.2—5.8) respec -tively. The following factors were found to have a positive effect of PFS at multivariate analysis: grade I—II adverse events to aflibercept therapy (hazard ratio (HR) 0.58; 95 % CI 0.38—0.89; p = 0.01), therapy for concomitant diseases (HR 0.47; 95 % CI 0.29—0.76; p = 0.002), and ECOG performance status of 0 (HR 0.53; 95 % CI 0.34—0.81; p = 0.004). Patient with all 3 factors present had median PFS of 9 months, whereas patients without them demonstrated PFS of only 3 months (HR 1.9; 95 % CI 1.5—2.6; p <0.001). Conclusions. Satisfactory performance status, adequate therapy for concomitant diseases, and adverse events to aflibercept therapy were associated with better PFS in patients receiving aflibercept-containing chemotherapy.

Background.  Urothelial cancer ranks 7th and 17th of all the malignant tumors in males and females, respectively. Development of new immunotherapeutic drugs provides new possibilities in treatment of such patients, especially the patient population in whom platinum‑based therapy is contraindicated. Administration of immunooncology drugs requires determination of PD-L1, for which various diagnostic systems are used. The question regarding correlation of results of determination of PD-L1 expression remains of concern. Materials and Methods.  The study was performed on 100 samples of surgical and biopsy samples of urothelial cancer. Two clones of 22C3 and SP142 with corresponding detection systems were used for the study. PD-L1 expression was assessed in tumor and immune cells. Results.  The study demonstrated a high correlation of negative PD-L1 tumor status determined using both diagnostic agents (92 % and 97 %) and low correlation of results of positive PD-L1 status (67 % and 43 %). Conclusions.  Thus, if a negative result of PD-L1 status of urothelial cancer is obtained using any of the diagnostic agents studied, repeated test with the other antibody is not required. If positive status is obtained in one test, the patient may have a negative status in the other test, which allows recommending a repeated testing in borderline cases using a test, recommended for the medicinal product untended for treatment.

Purpose . To assess the incidence and severity of adverse events; to explore clinical factors associated with grade 3–4 non-hematologic toxicity; to assess the immediate efficacy and progression-free survival during treatment with the FOLFIRI regimen in combination with aflibercept in Russia. Materials and Methods . A retrospective multicenter study has been conducted with data collected from 20 clinics in 15 regions of Russia. There was no statistical hypothesis. Progression-free survival was the main efficacy criterion. The statistical analysis was performed using IBM SPPS Statistics v. 20 software. Results . FOLFIRI and Aflibercept combination was administered to 264 patients. The mean number of treatment cycles was 6 (1 to 29). The toxicity of aflibercept was addressed by dose reduction and dosing delay in 10.1 % and 11.4 % of patients, respectively, and dose reductions and dosing delays in any of FOLIFRI components were reported in 20.1 % of participants. The objective response rate was 20.3 %. The median progression-free survival in patients receiving second-line treatment was 6 months (95 % CI: 5.3–6.6 months). Seventy-two percent of patients experienced any grade of adverse events most of which were limited to grade 1–2 (62.1 %). Non-hematologic toxicity was reported in 64 % of patients (grade 3–4 in 17.9 %). Hematologic events were detected in only 17.9 % of patients. Multifactorial analysis has shown that drug therapy for concomitant diseases (OR 1.98, 95 % CI: 1.04–3.78, p = 0.037) and the number of chemotherapy lines prior to aflibercept (ОR 1.5, 95 % CI: 1.06–2.11, p = 0.02) were independent predictors of grade 3–4 non-hematologic toxicity. Conclusions . Objective response rate, progression-free survival, and frequency of toxicity-related aflibercept discontinuations in the Russian study with patients receiving aflibercept in combination with FOLFIRI regimen as a second-line treatment has shown the results that were comparable with VELOUR study. Comorbidities requiring drug treatment and the number of prior chemotherapy lines appear to be risk factors for grade 3–4 nonhematological toxicity events.

Objective: to evaluate the prognostic value of clinical and pathomorphological stages in patients with rectal cancer after preoperative chemoradiotherapy and to assess the effectiveness of adjuvant chemotherapy in these patients. Materials and methods. We conducted a retrospective analysis of the data from a prospectively maintained database for patients with rectal cancer. The study cohort included patients with stages I–III rectal cancer that underwent preoperative chemoradiotherapy followed by surgical treatment performed in the Department of Proctology and Clinical Pharmacology and Chemotherapy between 2004 and 2013. The relapse-free and overall survival rates were assessed to estimate treatment efficacy. Results. A total of 457 patients were eligible for the study; of them 98 patients (21.4 %) received adjuvant chemotherapy. The following independent factors were found to negatively affect relapse-free survival: perineural invasion (р <0.01; hazard ratio (HR) 3.1; 95 % confidence interval (CI) 1.43–6.89), preoperative neutrophil-lymphocyte ratio ³ 3 (р = 0.01; HR 1.8; 95 % CI 1.37–2.42) and pathomorphological stage (р <0.01; HR 1.82; 95 % CI 1.37–2.42) (but not clinical stage). The pathomorphological stage (р <0.01; HR 1.9; 95 % CI 1.30–2.65), invasion into lymphatics (р <0.01; HR 2.4; 95 % CI 1.27–4.59) and white blood cell count ³ 11 000/µL (р <0.01; HR 13.1; 95 % CI 1.33–7.33) were independently associated with poorer overall survival. We observed a trend towards a decline in the relative risk of death in patients with stage yp3N0M0 cancer in response to adjuvant chemotherapy (р = 0.1; HR 0.4; 95 % CI 0.01–37.6). There was also a trend towards better relapse-free and overall survival in adjuvant chemotherapy-treated patients with stage ypT0–4N1–2 (р = 0.1; HR 0.65; 95 % CI 0.4–1.1 and р = 0.3; HR 0.3; 95 % CI 0.4–1.4 respectively) and stage yр T0–4N2M0 (р <0.01; HR 0.3; 95 % CI 0.14–0.70 and р = 0.03; HR 0.5; 95 % CI 0.2–1.0) cancer. Conclusion. In patients with rectal cancer, the pathomorphological stage appears to be a more reliable prognostic parameter compared to the clinical stage; this should be considered when prescribing adjuvant chemotherapy to patients that underwent preoperative chemoradiotherapy.

Представлен анализ публикаций, посвященных результатам повторных циторедуктивных операций при раке яичников, и собственный опыт выполнения данных вмешательств. Обсуждаются показания к выполнению повторных циторедуктивных операций и их результаты, прогностические модели, позволяющие оценить возможность выполнения полной повторной циторедукции. По данным ретроспективных исследований, повторные циторедуктивные операции увеличивают продолжительность жизни части больных с рецидивами рака яичников. Результаты единственного завершенного рандомизированного исследования неоднозначны. Критериями отбора кандидатов для этих вмешательств являются платино-чувствительный рецидив, наличие перспектив для дальнейшей химиотерапии, наличие одной или нескольких рецидивных опухолей. Повторная циторедуктивная операция целесообразна только при удалении всех макроскопически определяемых опухолей.

The process of angiogenesis is essential for the growth and spread of malignant tumours. Antiangiogenic therapy is deeply embedded in the standard treatment of disseminated ovarian cancer (OC). The numerous studies have demonstrated its efficacy in various stages of the therapy of this disease; bevacizumab is the best-investigated anti-angiogenic drug for OC. This article presents a review and analysis of the most significant studies of the efficacy of anti-angiogenic therapy in ovarian cancer, and describes various aspects of its use in this disease.

Introduction. The concordance of KRAS gene mutation status between the primary and metastatic CRC is 95%. The aim of this study was to find factors associated with the disconcordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumors and metastases in pts with CRC. Patients and methods. We performed DNA melting analysis with TaqMan probes and following Sanger sequencing to detect mutation hot-spots in KRAS exons 2 and 3, NRAS exons 2 and 3, BRAF exon 15, PIK3CA exons 9 and 20 in 148 tumor tissues from 65 pts (65 primary tumors and 83 metastases). Results. Mutations in KRAS, NRAS, PIK3CA and BRAF genes in primary tumors were detected in 43.1%, 3.1%, 13.8% and 3.1%, respectively. Discordance of mutation status of genes was identified in 29.2% of patients: 16.9% in KRAS, 3% in NRAS, 12.3% in PIK3CA and 3% BRAF status. In all cases of metastases in the brain we found the discordance in KRAS and PIK3CA mutation status (p=0.08). Also, peritoneal metastases had discordance in KRAS status (p=0.02). With the increase of period from removal of the primary tumor and metastases, the incidence rate of changes in the mutational status of the genes also increased. Conclusion. discordance of the mutational status of genes, especially in the long course of the disease, raises the question of repeating biopsies in the progression of the disease

Background. Epithelial-mesenchymal transition (EMT) is a factor related to metastatic potential of tumor cells. The most distinguishing feature of this transformation is expression of protein vimentin, which is not common for epithelial cells. Data of EMT level and clinical significance of the marker is ambiguous in prognosis of tumor different localization including ovarian cancer. Objective is characterization of EMT in ovarian cancer tissue based on quantitative analysis of co-expression level of epithelial cytokeratins and mesenchymal cells marker vimentin. Materials and methods. A quantitative assessment of co-expression level of cytokeratins and vimentin was performed by double immunofluorescence staining method (58 surgery specimens of ovarian cancer stage III), associated with flow cytometry. Results. Double immunofluorescence staining method, developed and used in the current study, was used for quantitative assessment of EMT level based on value of cytokeratin and vimentin co-expression in epithelial cells. Epithelial cells co-expressed these markers, were detected in 100 % tumor investigated with individual value differences from 10 to 86 %. Average co-expression level of cytokeratins and vimentin in subgroups with high and low level value related to median 42 % significantly varied and were 28,5 ± 7,5 and 56,3 ± 11,8 % (p = 0,02) respectively. Conclusions Serous ovarian cancer is molecular heterogeneous group with principal differences in level of EMT tumor phenotype between various patients. In half of the cases the disease is characterized by high metastatic potential of tumor cells. Co-expression of cyto-keratins and vimentin in all the tumors investigated is evidenced clinical significance of this molecular characteristic in ovarian cancer pathogenesis.

Цель. Оценить качество оказания медицинской помощи больным раком толстой кишки в РФ. Материалы и методы. Проведен опрос 17 клиник 14 регионов РФ (рис. 1), включавший параметры, которые потенциально могут влиять на смертность больных метастатическим раком толстой кишки. Применялся корреляционный и регрессионный анализ ассоциации смертности от рака толстой кишки и данных анкетирования. Результаты. По результатам регрессионного анализа подтверждено обратное влияние на смертность при раке толстой кишки назначения адъювантной химиотерапии после удаления первичной опухоли (р=0,01), назначения бевацизумаба в первой линии терапии (р=0,01), подтверждена тенденция к уменьшению смертности при установке центрального венозного доступа (р=0,07), при назначении анти-EGFR антител в первой линии (р=0,1). Отмечена значимая взаимосвязь между высокой смертностью в регионе и назначением монотерапии фторпиримидинами в первой линии лечения метастатического рака (р=0,01). Выводы. На смертность при раке толстой кишки влияет комплекс факторов, отражающих организацию оказания противоопухолевого лечения в регионе как на этапе лечения больных ранними стадиями (например, назначение адъювантной химиотерапии), так и с метастатическим процессом (например, характер первой линии терапии).