Objective. To estimate the frequency of germline mutations in homologous recombination genes in a population of patients with pancreatic cancer and to assess the possibility to predict the risk of mutation carriage based on the clinical and anamnestic data.

Materials and methods. The study included patients diagnosed with pancreatic cancer, blood samples of which were taken to detect clinically significant germline mutations in the BRCA1, BRCA2, CHEK2, BLM, NBS1, and PALB2 genes. Clinical data and family history data were collected for each patient.

Results. The study included 99 patients. Mutations in BRCA1 gene were detected in 4 % of cases, in CHEK2 gene – in 2 %. No mutations were detected in the BRCA2, as in BLM, NBS1, and PALB2 genes. Localization of primary tumor, presence of distant metastases, stage of disease, family history of malignant neoplasms did not correlate with the risk of BRCA1 mutation (p>0.05). The patient’s eligibility for NCCN criteria for BRCA1 gene mutation diagnosis proved to be a significant marker of germline mutation presence (p=0.043).

Conclusions. NCCN criteria for genetic testing are the best predictor of BRCA1 germline mutation in patients with pancreatic cancer.

Poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare malignancies, most of which are characterized by aggressiveness, a tendency to rapid metastasis and an unfavorable prognosis even when localized. In 2017 World Health Organization (WHO) updated classification of GEP NENs and recognized the category of well-differentiated pancreatic NET G3, associated with Ki‑67 index usually over 20%. The upper level of Ki‑67 is not defined. Usually it is 55%. Highgrade poorly differentiated pancreatic NENs are defined as pancreatic neuroendocrine carcinomas (panNECs). Although the NET G3 category is recognized for pancreatic neuroendocrine neoplasms only, many specialists consider it reasonable to apply this term to all well-differentiated GEP NETs with Ki‑67 index in the 20 to 55 percent range. Clinical behavior and therapeutic approaches for advanced GEP NECs and NETs G3 are different. Standard palliative chemotherapy for GEP NECs consists of cisplatin or carboplatin combined with etoposide. The second-line regimens include irinotecan-, oxaliplatin, fluoropyrimidine- and temozolomide-based regimens. Temozolomide-based chemotherapy regimens, as well as targeted therapy are more preferable as first line therapy for patients with NETs G3. The platinum-based chemotherapy regimens are considered at the time of disease progression. Further clinical studies with the inclusion of much more patients will determine the optimal treatment strategy for this category of patients.

Chemotherapy-induced nausea and vomiting (CINV) has tremendous negative impact on daily life of cancer patients and their quality of life. In this article we analyzed current clinical guidelines in preventive measures and treatment of CINV as well as efficacy of recommended standard regimens for CINV prevention in patients receiving high emetogenic chemotherapy (HEC). We summarized existing data about olanzapine – affordable antipsychotic agent with potent antiemetogenic activity which is quite useful for CINV prophylaxis in patients receiving HEC. We highlighted possible future directions for research of olanzapine in oncology and reasons that preclude integration of this drug in routine clinical practice in Russia.

Therapy with immune checkpoints inhibitors (anti-PD-1 therapy) has become the standard of care for metastatic renal cell carcinoma (mRCC) patients with resistance to tyrosine kinase inhibitors (TKI). Identification of reliable predictive markers for anti-PD-1 therapy would help to select patients who are most likely to respond to checkpoints inhibitors. This article represents the results of treatment of 23 mRCC patients who received nivolumab as part of the expanded access program in Russia. All patients demonstrated resistance to previous lines of TKI therapy. Overall response rate for nivolumab was 21.7 % with median progression-free survival of 4 months (95%CI=1.37–10.04). The median overall survival was not reached with the median follow-up of 10 months (3–14 months). The grade 3–4 toxicity was observed in 3 (13 %) pts. Favorable MSKCC prognosis before treatment, the initial level of sPD-1 exceeding the estimated threshold value and the development of any grade hypothyroidism after treatment initiation were associated with greater progression free survival. The number of preceding lines of TKI therapy, the level of PD-L1 and FOXP3 expression on tumor-infiltrating leukocytes (TILs) did not significantly affect progression-free survival in this group of mRCC patients. The ef ficacy and toxicity profile of nivolumab corresponded to the results of phase 2–3 trials.

Introduction. Due to anatomical features, surgical treatment of oral cancer can lead to significant functional and esthetic defects. Main methods of reconstruction can be divided into groups of local and free flaps. There are lots of publications devoted to reconstruction of defects of oral cavity with the use of local and free flaps, but only few of them contain the comparison of these methods in the aspect of functional results.
Materials and methods. A total of 58 patients with oral cancer were included in our study. All patients received surgical treatment with one-time reconstruction of defect. In 34 cases we used free radial flap and in 24 – submental local flap.
Results. The use of submental flap has advantages in the intraoperative time, time of recovery, functional results, with the same locoregional control.
Conclusions. We suggest submental local flap and radial free flap to be the method of choice in reconstruction of mucosa and soft tissues defects in patients with primary and recurrent oral cancer.

The purpose of the study was to assess the infection of tumor tissues with herpesviruses and human papillomavirus (HPV) in patients with squamous cell carcinoma of the larynx (SCCL) and to reveal the impact of viral infections of tumor tissues on the effectiveness of neoadjuvant therapy. DNAs of HSV1,2, CMV, EBV and HPV were studied by PCR in 26 samples of tumor tissues. We revealed a high level of herpesvirus infection in SCCL tumor tissues (up to 92.3 %), while HPV infection was less frequent – 19.2 %, including low-risk HPV (LR HPV, 11.5 %) and high-risk HPV (HR HPV, 7.7 %). Significant differences in the detection rates of the studied pathogens were found (p<0.05). EBV was more frequent (73.1 %), and HSV1,2 detection rate was the lowest (7.7 %). The prevalence of herpesvirus presence in tumor tissue in the absence of HPV was detected (p<0.05). The effectiveness of therapy was higher in patients without viral infections, compared to infected patients (100.0 vs. 80.0 %), but the difference was nonsignificant (p>0.05). There was no significant dependence of the chemotherapy effectiveness on the type of infection (p>0.05). However, the presence of LR HPV, HSV1,2 and especially combinations of herpesviruses with HPV in tumor tissues reduced the number of cases of tumor stabilization and regression which is notewor thy and requires fur ther research.

Aim. To evaluate the effectiveness of different regimens of maintenance chemotherapy after the first line of treatment for patients with metastatic colorectal cancer.

Materials and methods. We performed retrospective analyses of the data from 432 patients from 17 clinics in 14 regions of the Russian Federation who started systemic therapy for metastatic cancer in 2013. The main inclusion criterion was objective response or stabilization after the first 16 weeks of first-line therapy. Four groups of patients were compared, depending on the nature of maintenance therapy: those receiving fluoropyrimidines, a combination of fluoropyrimidines with bevacizumab, monotherapy of bevacizumab and monotherapy of anti-EGFR antibodies. The main criteria for assesment of the effectiveness of treatment were progression-free survival and overall survival. The statistical analysis was performed with the SPSS 20.0 sof tware package.

Results. Maintenance therapy after completion of the first 16 weeks of the 1st line of chemotherapy was administered in 126 patients, most of them were treated with fluoropyrimidines (53.1 %). The median overall survival in the maintenance group was 27 versus 21 months in the observation group, p=0.01, HR=0.78 (95 % CI 0.6–1.02) Median progression-free survival in the maintenance group was 11 vs 7 months in the observation group (p<0.001, HR=0.6, 95 % CI 0.5–0.8). The worst results of progression-free survival were observed in the group with monotherapy of bevacizumab – median was 10 months versus 12 months in the fluoropyrimidine monotherapy group, 10 months for the combination of fluoropyrimidine with bevacizumab and 14 months for monotherapy of the anti-EGFR (p=0,9, HR=1.0, 95 % CI 0.9–1.2).

Conclusions. There were no statistical differences in survival with different regimens of maintenance therapy. Monotherapy of bevacizumab in maintenance treatment was associated with the worst sur vival rates.

Triple-negative breast cancer (TNBC) comprises 12–20 % of all breast cancers. TNBC is defined by the absence of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC is a heterogeneous disease, with an aggressive clinical feature, a higher risk of both local and distant visceral and / or brain metastases. Recurrence usually develops between 1 and 3 years after the initial diagnosis and most deaths occur within 5 years. Epidemiologic studies illustrate a high prevalence of triple-negative breast cancers among young women. Triple-negative breast cancer is also more likely to occur in women that carry a BRCA mutation, especially if they are diagnosed at a young age. Cytotoxic chemotherapy remains the mainstay treatment for TNBC because there are currently no specific targets for treatment options (hormone receptors or HER-2 amplification). Chemotherapy combined with targeted agents including DNA repair with PARP inhibitors, EGFR inhibitors, anti-angiogenic agents and a Chk1 inhibitor produced modest improvement in response rate and overall survival. Nevertheless there’s no common standards for treatment such patients with metastatic TNBC. Progress in the development of new regimens and combination of drug treatment agents for patient with generalized TNBC remains an important challenge that could lead to improvement immediate and long-term outcomes.

The appearance of anti-PD-1 drugs significantly improved prognosis of patients with metastatic skin melanoma. However, little data on the effectiveness of these drugs in the second and subsequent lines of therapy has been accumulated in the international literature. We have analyzed our experience in the use of nivolumab in the treatment of metastatic melanoma. This non-randomized, uncontrolled, continuous study included 53 patients with metastatic or unresectable melanoma, of whom 86.8 % (46) received two or more lines of systemic therapy for metastatic melanoma. The rate of objective response was 22.6 % (95 % Confidence Interval (CI) 53.3–64.4 %). The median progression-free survival was 4.37 months (95 % CI 2.27–6.47). The median overall survival was 17.9 months (95 % CI 8.89–26.99). One-, two-, three-year overall survival contained 66, 35 and 35 %, respectively. The efficacy of nivolumab in the second and subsequent treatment lines is significantly lower than showed in the results of randomized trials of the use of anti-PD-1 drugs in the first line of therapy.

The choice of treatment strategy in patients with stage IIIC‑IV ovarian cancer (OC) remains the subject of numerous discussions. The reason for this is the unsatisfactory results of randomized trials and the low frequency of primary complete debulking surgery in these studies. We conducted a retrospective analysis to evaluate the survival outcomes in patients with OC stage IIIC–IV (n=314) who underwent treatment between 1995 and 2017. The median progression free survival for primary surgery was 15.6 months, after interval debulking – 11.5 months (p=0.002, HR 0.61: 95 % CI 0.39–0.81). The primary cytoreduction significantly increased the median of overall survival by 19.6 months: from 38.0 months after interval debulking up to 57.6 months after primary cytoreduction (p=0.04, HR 0.64: 95 % CI 0.41–0.99). An increase in the number of optimal interval debulking does not lead to an improvement in the long-term results of treatment in the group of patients after neoadjuvant chemotherapy. Our analysis over the past 20 years has shown that improvement in treatment outcomes is only observed in the primary cytoreduction group due to an increase in the number of complete optimal cytoreductive surgery.