In 2005 the Oxford meta-analysis of individual patient data from many trials showed no benefit to postmastectomy radiotherapy in node-negative breast cancer patients but reduced 5-year local recurrence and 15-year breast cancer mortality in patients with node-positive disease who underwent axillary lymphnode dissection. Despite these data, there is still some debate over the appropriateness of postmastectomy radiotherapy in patients with 1 to 3 involved lymph nodes. Neoadjuvant chemotherapy leads to clinical and pathological response in a certain proportion of patients. So far, the universal approach was to ignore the information on response to chemotherapy and recommend postmastectomy radiotherapy based on pre-chemo clinical disease status. The main goal of this article is first to summarize the evidence for the use of postmastectomy radiotherapy in a more traditional treatment sequence, and then show new evidence that highlights how information about the response to chemotherapy can be incorporated into the decision regarding the need and benefit of postmastectomy radiotherapy in the context of neoadjuvant chemotherapy. 

Hepatocellular carcinoma (HCC) in vast majority of cases develops on the background of the chronic liver diseases, more often – viral hepatitis B and C, and is diagnosed at the advanced stages [1, 3]. Despite the advantages of the modern oncology (some patients live till appearance of brain metastases [1]), prognosis in HCC is still poor. In general, prognosis depends on not only biological characteristics of the tumor itself, but also on the background of the liver condition, often – at the stage of the cirrhosis. As distinct from the other malignant tumor of liver – cholangiocellular carcinoma, there are no universal prognostic classifications for HCC [2]. International classification TNM used for majority of solid tumors is not appropriate to be ‘reference’ for HCC [4]. There are several prognostic scales and classifications created recently in West and Asian countries. For the creation of such systems they use more often the regression model on the basis of prognostic variables of the investigated population. Currently, there is no universal prognostic classification or scale for HCC ГЦР. Almost all these classifications included the features; liver function, tumor characteristics, clinical behavior, undercurrent diseases, presence of the cirrhosis [3]. 

Clinical trials of metformin efficacy in breast cancer were reviewed in this article. According to some data from cohort and case-controlled studies, the use of metformin with combined therapy of breast cancer improves overall and disease-free survival. Initial data from randomized clinical trials of metformin in adjuvant and neoadjuvant therapy of breast cancer are expected in the nearest future. 

It is well known that metformin is widely used for the treatment of type II diabetes mellitus. However, in numerous epidemiological studies it was shown that patients taking metformin were less likely to have cancer of different localization and had better survival prognosis. Many researchers consider metformin to be a targeted metabolic drug that has many goals: it acts on mitochondria, affects intracellular signaling, blocks channels, inhibits the formation of endothelial and platelet growth factors, reduces the level of vitamins involved in the synthesis of nucleotides and amino acids, etc. It has also been established that metformin belongs to the group of “metabostemness” drugs, that is, it acts on cancer stem cells, blocking their division. We conducted a survey study that highlights the most important mechanisms and fields of application of metformin. The study of the use of this drug in oncology will make it possible to understand the pathogenetic targets of metabolic therapy and the prevention of cancer. 

Sunitinib is one of the main drugs for the first line therapy for clear cell metastatic renal cell carcinoma (mRCC). At present, in order to achieve the optimal level of concentration of the drug in the plasma, the standard therapy regimen is 4/2 – 4 weeks of daily intake of 50 mg of sunitinib followed by a break for 2 weeks. However, with this scheme, side effects are often encountered. It makes necessary to reduce the dosage of the drug. Over the past few years, there is a growing evidence of the effectiveness of the scheme 2/1 – 2 weeks of taking sunitinib at 50 mg per day, followed by a break for a week. This scheme allows to maintain the necessary concentration of the drug in the plasma. This, in its turn, reduces, the rate of side effects. In this article, a review of the literature on the efficacy of sunitinib using scheme 2/1 in patients with mRCC is given. 

This review presents a current understanding of PD-1/PD-L1 inhibitors. In spite of unprecedented clinical efficacy of checkpoint inhibitors in some cancer types, primary or acquired resistance to anti-PD1 therapies is common and affecting up to 60% of patients in some cancer types. The mechanisms that contribute to the development of anti-PD1-/PD-L1 resistance are also discussed. 

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 

The study included 73 women with stage III HER2-positive locally advanced breast cancer (BC) which received simultaneous chemoradiotherapy in combination with targeted therapy. Patients were stratified into two groups: in the first group patients in the neoadjuvant received concomitant chemoradiotherapy in combination with trastuzumab, in the second group patients were prescribed no targeted therapy. The therapy with trastuzumab appeared to be the most effective. 3-year survival rate in the first group was 85.5%, 73.3% – in the second group, 5-year survival rate was 73.9% and 40.3% respectively (p<0.05). Herewith, disease-free survival was higher in the trastuzumab group, but the difference did not reach statistical significance. 3-year disease-free survival rate in the first group was 71.4%, 47.6% – in the second group, 5-year disease-free survival was 40.9% and 26.0% respectively (p=0.06). In addition, the study analyzed the influence of radical mastectomy surgery on long-term outcomes, and explored the efficacy of different fractionation regimes. The findings led to the conclusion that the combined chemoradiotherapy in combination with targeted therapy is an effective treatment for patients with the HER2-positive locally advanced BC. Provided that this therapy is not inferior to the comprehensive treatment which includes surgery and can be used as an independent method of treatment without surgery and associated complications.

The combination of ELF (etoposide, 5-fluorouracil, leucovorin) for metastatic gastric cancer is used since 1980-ies, but until recently, is also often used in modern chemotherapy of metastatic gastric cancer. In the modern arsenal of anticancer combinations for the treatment of metastatic gastric cancer there is a number of new modes with the incorporation of docetaxel, irinotecan, oxaliplatin and place of the combination of ELF in anticancer chemotherapy of gastric cancer is unclear. In our study, we analyzed 60 histories of patients of the departments of clinical pharmacology and chemotherapy. We studied immediate and long-term results of treatment with a combination of ELF for their own group of patients. All patients were treated 344 therapeutic cycles of chemotherapy, median courses was 6 (1–6). Treatment failed to gain control over the symptoms of the disease failed in 23 (38,3%) patients. As a result of chemotherapy, 8 patients (13.3%) showed partial tumor response. 40 patients noted stabilization of the process (66.6%). For immediate results – the median overall survival was 8.4 months. Given the low toxicity, a high percentage of the disease control and control of clinical symptoms of the disease treatment has every right to exist and use in clinical practice as an induction first-line chemotherapy of metastatic gastric cancer. 

Evaluation of the effect of the clodronate therapy on the dynamics of chronic pain syndrome and on the quality of life of patients with breast cancer with metastatic lesions of bones after previous treatment with drug containing zoledronic acid. Topicality: Breast cancer is characterized by tendency to early metastasize: about 6% of patients already at diagnosis have metastatic form of the disease. The most frequent targets are the bones: for the frequency of bone metastasis, breast cancer is on the second place among malignant tumors and for the specific weight on the first place [1, 2, 3, 4]. On the early stages, metastatic bone lesions can be asymptomatic. 

Gliomas are common primary brain tumors in adults. This high degree of glioma malignancy is characterized by a disappointing outlook, despite the modern approaches to treatment. Therefore cases of prolonged relapse-free period of the disease, as well as treatment regimen and control regimen concerning gliomas with high degree of anaplasia are of exceptional interest. Even more exceptionally interesting is the drug bevacizumab, which in our clinical practice allowed to provide the patient with the diseasefree high-grade glioma from 2012 year to the present. 

Malignant ovarian germ cell tumors (MOGCT) generally affect young women. The optimal volume of surgical treatment is unilateral adnexectomy. BEP-regimen chemotherapy (ChT) is the most effective regimen of treatment. Since this disease affects mainly adolescents and young women of reproductive age, one of the most important priorities concerning this category of patients is the fertility preservation.

The aim of this study was analysis of long-term effects of ChT on reproductive function in a large population of young women treated for MOGCT in our center.

Materials and methods. Inclusion criteria in our study were MOGCT, fertility-sparing surgery, cisplatin- and etoposide-based induction ChT (BEP/EP regimen), age 16-49 years. Presence of menstruation before treatment; no relapse following ChT at least 1 year. Blood tests were taken for hormones of ovarian function (follicle-stimulating hormone, luteinizing hormone, estradiol, anti-Mullerian hormone (AMH), inhibin B) to assess their menstrual, reproductive function, post therapeutic status of pregnancy or delivery.

Results. The median time from the end of ChT until the date of filling out the questionnaire was 90 months (12–228 months). 58 (93.5%) of the 62 patients received BEP/EP regimen as a first line treatment, 4 (6.5%) treated with other regimens. During the ChT 42 (71.2%) patients developed amenorrhea due to the toxic effect of ChT. Among 47 women with regular menstruation after completion of ChT 23/47 (49%) patients attempted conception, 18/23 (78.3%) women conceived, 20 live birth deliveries were received. Correspondingly there were 2/18 (11%) miscarriages and 6/18 (33.3%) terminations. Four women were pregnant at the moment of the analysis. Inhibin B level was normal in all 15 evaluated pts (median 74,4 pg/ml, range 10–120). Median of AMH level was 0,97 ng/ml (range 0.08-6). In 10 (52.6%) of 19 pts AMH level was < 1 ng/ml, that was considered a decrease of ovarian reserve. 

In metastatic breast cancer (MBC) the combination of Bevacizumab (Avastin) and chemotherapy (CT) failed to demonstrate an increase in overall survival with a significant improvement of the objective response rate and progression-free survival (PFS) in randomized trials of the 3d phase. Nevertheless, observational studies in the daily clinical practice for the use of Bevacizumab in MBC continue in the world. We present the results of our own observational study, which goal is to assess the efficacy and tolerability of Bevacizumab in combination with CT in patients with HER/2-negative metastatic and locally advanced breast cancer. The study included 34 patients with breast cancer (6-locally advanced, 28-metastatic) at the age of 29 to 66 years (mean – 49.5). Bevacizumab was administered at a dose of 7.5 to 15 mg/kg every 3 weeks in combination with CT. In total, the patients received 294 doses of Bevacizumab (median – 10). All patients with locally advanced breast cancer were operated on after the treatment completion, a pathologic complete response was registered in 33.3%. In MBC, the objective response was registered in 46,4%, tumor growth control in 89.3%, median PFS – 10 months. Typical for Bevacizumab adverse events, such as hypertension, proteinuria, were moderate and were met respectively in 14.7% and in 5.9% cases. In 1 (2.9%) patient the treatment was complicated by deep vein thrombosis and PE due to disease progression. Conclusion. Bevacizumab in combination with CT in breast cancer treatment can achieve high rates of objective response and PFS independent of the treatment line

The article presents the results of the meeting of the Advisory board “Prospects for study and use of eribulin in advanced breast cancer”, held on May 16, 2017, to discuss new data on the eribulin mechanism of action, the Russian experience with eribulin in real clinical practice and obtain expert opinions on the perspectives of study of eribulin use for breast cancer.