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Objective. To assess the overall and disease-free survival rates in patients with EGFR-mutated lung adenocarcinoma, who underwent surgery after achieving the objective response to tyrosine kinase inhibitor (TKI) therapy.Material and Methods. The overall and disease-free survival rates were analyzed in 18 patients with EGFR-positive lung adenocarcinoma, which was inoperable at presentation due to locally advanced disease or the evidence of distant metastasis. In accordance with the clinical standards, patients were recommended for TKI therapy. Surgical resection was performed after achieving the objective tumor response to TKI therapy. The control group included 23 patients with EGFR mutation-positive lung adenocarcinoma, who did not undergo surgery after receiving TKI therapy.Results. The study revealed a statistically significant effect of surgical resection on the overall survival (OS) in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma after response to TKI therapy (p=0.004). However, there was no statistically significant effect on the disease-free survival (DFS) (p=0.40). There was a tendency to increase in the median OS in patients of the study group (46 months) compared to that in patients of the control group (26 months). Surgery in the study group was characterized with some technical difficulties associated with severe fibrosis. However, this did not affect the duration of surgery and the volume of blood loss.Conclusion. Tumor resection in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma is feasible and safe, but requires highly qualified team surgeons in well-equipped medical centers. Our study revealed that the combination of EGFR-TKI and tumor resection provided better PFS and OS than EGFR-TKI alone. However, further studies are required.

Objective: to compare the efficacy and toxicity of aflibercept and bevacizumab in combination with fOLfIRI in secondline therapy for patients with metastatic colon cancer.Materials and methods. we performed a retrospective analysis of data on patients with metastatic colon cancer treated in 9 clinics in the Russian federation. The inclusion criteria were as follows: metastatic or locally advanced colon cancer; treatment with bevacizumab or aflibercept plus fOLfIRI in the second-line therapy. The primary outcome measure was progression-free survival (PfS). Secondary outcome measures included objective response rate and incidence of adverse events.Results. A total of 271 patients with metastatic colon cancer who received second-line therapy with bevacizumab (n = 81) or aflibercept (n = 190) between 2014 and 2018 were selected for this study. Study groups were matched for main prognostic signs. The objective response rate was 18.1 % in the bevacizumab group and 20.5 % in the aflibercept group (p = 0.7). The median PfS was 5 months (95 % confidence interval 3.8–6.1) in the aflibercept group and 7 months (95 % confidence interval 0.81–2.1) in the bevacizumab group (hazard ratio 1.4; 95 % confidence interval 0.99–2.1; p = 0.04). multivariate regression analysis demonstrated that the type of the targeted drug independently had no effect on PfS (hazard ratio 1.3; 95 % confidence interval 0.9–1.9; p = 0.2). we observed no statistically significant differences in the incidence of complications of any grades between the groups (58 % vs 72 %, p = 0.1). Patients receiving aflibercept were more likely to develop grade III–Iv arterial hypertension (2 % vs 9.5 %) and diarrhea (0 % vs 5.4 %), whereas thrombotic complications were more common in the bevacizumab group (10 % vs 1.8 %).Conclusion. we observed no significant differences in objective response rate and PfS between patients with metastatic colon cancer receiving bevacizumab or aflibercept in combination with fOLfIRI as second-line therapy. The toxicity profiles were different. Our findings can be used for choosing an optimal targeted drug for second-line treatment.

Purpose of the study. There is the generalized analysis of administration of vinflunine in real clinical practice in St.Petersburg Clinical Scientific and Practical Center of Specialized medical Care (oncological).Materials and methods. This analysis gathered 27 patients with urothelial carcinoma treated using this medicine in St.Petersburg Clinical Scientific and Practical Center of Specialized medical Care (oncological). We assessed efficacy, safety profile of vinflunine in this subset of patients.Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 51,86 %, one patient demonstrated complete response. Median of response duration accounts for 3,4 months. Adverse events were observed in 28,4 %, most of them were 1-2 grades. 2 patients stopped therapy due to adverse events.Conclusion. In our analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, confirm expediency to administer of vinflunine for metastatic urothelial carcinoma.

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 compare the efficacy and tolerability of second‑line chemotherapy with original bevacizumab (Avastin) and biosimilar bevacizumab produced by “Biocad” (Avegra) in patients with metastatic colon cancer.Materials and methods. This retrospective observational study included patients with metastatic colon cancer treated in 9 clinics in the Russian Federation. Inclusion criteria were as follows: metastatic or locally advanced colon cancer and second‑line therapy with bevacizumab (Avastin or Avegra). The primary outcome measure was overall survival (OS). Secondary outcome measures included progression‑free survival (PFS), disease control rate (DCR), and incidence of adverse events associated with antiangiogenic therapy.Results. We identified 209 patients with metastatic colon cancer who received second‑line therapy with biosimilar bevacizumab (n = 37; 17.7 %) or original bevacizumab (n = 90; 43 %) or no targeted therapy (n = 82; 39.3 %) between 2014 and 2018. Patients in these three groups were matched for their main prognostic characteristics. The DCR was 59.5 % in the group of biosimilar bevacizumab, 58.9 % in the group of original bevacizumab, and 50 % in the control group (without targeted therapy). PFS was 6 months in the chemotherapy group and 8 months in the groups of bevacizumab (hazard ratio (HR) 0.77; 95 % confidence interval (CI) 0.65–0.91; p = 0.002); the difference in PFS between patients receiving biosimilar bevacizumab and original bevacizumab was insignificant (HR 1.3; 95 % CI 0.81–2.1; р = 0.3). Median OS was 16 months in the chemotherapy group, 30 months in the biosimilar bevacizumab group, and 20 months in the original bevacizumab group (HR 0.89; 95 % CI 0.72–1.1; р = 0.3). We observed a tendency to longer OS in patients receiving biosimilar bevacizumab (HR 0.44; 95 % CI 0.17–1.1; р = 0.08). Bevacizumab‑ associated toxicity was limited to arterial hypertension and was registered in 4 patients with only one patient who developed grade III hypertension.Conclusions. There was no significant difference in PFS between patients receiving biosimilar and original drug, while OS was higher in the group of biosimilar bevacizumab. Both medicines demonstrated similar toxicity. Therapy with biosimilar bevacizumab ensured lower incidence of hypertension and proteinuria compared to the original drug. An additional prospective observational study assessing the efficacy and tolerability of biosimilar bevacizumab in colon cancer patients is needed.

Background. Clinical reports on the coronavirus disease 2019 (COVID-19) suggest its higher incidence and worse outcomes in cancer patients. Considering a rapid pace of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic, more data on the risk of contagion and syndrome course is required with this patient group.Aim. Estimation of the infection rate in cancer patients managed at the Oncology Centre.Materials and methods. This retrospective study included cancer patients managed at the Oncology Centre between 9 April 2020 and 27 May 2020 and routinely tested for SARS-CoV-2 in polymerase chain reaction (PCR) assays and/or COVID-19 in chest computed tomography (CT).Results and discussion. A total of 2,628 patients were included in the study, with 119 (4.5 %) confirmed to have COVID-19; 45/119 were PCR-positive, 95/119 had viral pneumonia in CT, 21/119 were positive for both tests. A total of 47.9 % cases were asymptomatic, 11.8 % revealed a mild single-symptom disease. COVID-19 ended in death in 2 (2.5 %) of 80 cases with a known outcome. In PCR results of both patient and staff screening, the virus detection rate was 3.0 % and 2.4 %, respectively (p = 0.33).Conclusion. A COVID-19 screening revealed no significant difference in the risk of contagion between cancer patients and staff of the Oncology Centre. PCR tests may perform false negative for COVID-19 in cancer patients and should be coupled with CT scanning. The infection is asymptomatic or clinically mild in most other cases.

Aim. Assessment of the utility and advantage of videoendoscopic inguinal femoral lymphadenectomy (VE-LAD) over the standard open technique (OLAD) in patients with malignant skin melanoma and metastatic lesions of regional inguinal and/or femoral lymph nodes.Materials and methods. The Saint-Petersburg Clinical Research Centre for Specialty Medical Aid in Oncology managed 86 inguinal femoral LADs in melanoma patients over 2013–2016. VE-LAD was rendered in 48 (54.7 %) cases, and OLAD otherwise.Results and discussion. A total of 72 patients were included in the study. VE-LAD was performed in 48 (54.7 %) cases, and OLAD otherwise. An average VE-LAD duration was 90 (60 to 160) min. Severe complications were observed in 4/48 (8 %) VE-LAD and 16/24 (66 %) OLAD cases, which reveals a significantly lower complication rate in the study cohort (chi-square p > 0.000). Lymphorrhoea was shorter in the study cohort (> 7 days in 5 patients vs. 3/24 and > 14 days only in 11/24 OLAD cases; chi-square p > 0.000). No significant differences in relapse-free survival were observed between the cohorts, with higher absolute values of 22.6 months in the VE-LAD (95 % CI 14.8–30.4, p = 0.087) vs. 9.4 months (95 % CI 0.0–18.9, p = 0.087) in OLAD cohort. A median OS was 52.3 months (95 % CI 30.5–74.1, p = 0.996) in the VE-LAD vs. 39.9 months (95 % CI 30.6–49.2, p = 0.996) in OLAD cohort.Conclusion. Videoendoscopic inguinal femoral lymphadenectomy allows a radical inguinal femoral lymph node removal alike in conventional surgical dissection. Our results indicate the method performance towards reduced postoperative wound complications. The oncological indicators are comparable to the traditional surgery cohort.

Background. Malignant melanoma is steadily exaggerating over the recent decades. Nonetheless, improved systemic therapies have substantially increased life expectancy in patients with a locally advanced or disseminated disease. Higherincidence recurrent melanocytic skin lesions become essentially problematic and require more attention and control.Aim. Cross-survey on the incidence of synchronous multiple primary melanomas in patients with solitary melanoma and those with other operable solid tumours.Materials and methods. A total of 289 patients with suspected malignant pigmented skin melanoma were included in the survey. Patients were divided in two cohorts by the presence of primary skin melanoma and its tractability for radical excision. Patients with operable melanoma comprised the study cohort, and those with other solid tumours were the control.Results and discussion. The survey covered 289 patients, with 148 in the study and 141 in the control cohort. The study148 patients revealed 112 malignant pigmented melanomas, but none in the control cohort. A chi-square statistical analysis of clinical values in single and multiple melanoma cases showed a slightly higher prevalence of first-visit melanomas in patients with synchronous tumours (30% pT4 — p = 0.007).Conclusion. The observed 10% rate of second melanoma in the study cohort and a zero melanoma incidence in the control support the alternative hypothesis of a higher rate of newly detected melanomas in primarily diagnosed melanoma patients vs. those with solid tumours.

Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study.

Introduction. The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods. The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results. 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings. The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

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

Introduction. This article presents data on the manifestations of changes in the microenvironment of the peritoneal cavity in patients with carcinomatosis, expressed by the mineralization of the peritoneum, which in turn leads to functional changes in drainage of the peritoneal cavity.Materials and methods. We examined autopsy tissue of the peritoneum with symptoms of carcinomatosis and intact peritoneum using comparative scanning electron microscopy.Results and discussion. The study of the ultrastructure of peritoneum in patients with PC, revealed the phenomenon of SLL mineralization. The resulting elemental composition profile showed a high content of Ca, P, Na.Conclusions. 1. Carcinomatosis is not a local, but rather a systemic process. Determining the role of mineralization in carcinomatosis is of fundamental importance in carcinogenesis. 2. The serous membranes mineralization in patients with carcinomatosis can become a new treatment target, the impact on which may increase life expectancy and improve the quality of life. 3. The serous membranes demineralization can serve as a part of a combination treatment that includes the subsequent endolymphatic anti-tumour drug therapy.

Introduction. Ovarian cancer is characterized by complex diagnostics and flow forecasting, which makes it important to search for prognostic criteria. However, the prognostic significance of some factors has not yet been studied.The purpose of the study: to identify the features of immune response in the localization of metastases in the large omentum in ovarian cancer.Tasks: to reveal the pathomorphological features of the cellular immune response to metastases in the large omentum in patients with ovarian cancer II–III stages; to conduct histomorphometry of elements of the immune system in the area of metastases.Material and methods. The study was carried out on the biomaterial of the large omentum of 94 women with ovarian cancer II–III stage. The measurements were carried out on paraffin sections stained with hematoxylin and eosin and included evaluation of the following parameters: the number of lymphocytes in the field of view at the border and away from the tumor, the continuity of the lymphocyte shaft at the border with the tumor, the number of neutrophils on the border with the tumor, the presence of plasmocytes on the border with tumor. The preparations were studied and photographed under a microscope with a microscope-microvision mVizo-103 and a microscope Micromed 3.The results. Observed 94 patients with stage II–III ovarian cancer. Over the three-year follow-up period, the disease-free survival rate was 79.8%. A total of 64 patients with stage III disease were observed. A recurrence-free survival rate among patients with stage III ovarian cancer was 74.32%. Without relapse during the follow-up period, those patients were found whose lymphocytes formed a continuous shaft at the border with the tumor, their number in the field of view ×200 was 400 or more, the plasmocytes were present in the composition of the shaft, and the neutrophils were absent or few.The conclusion. A detailed histological study to quantify and qualitatively determine the severity of lymphoid elements of the large omentum allowed an indirect assessment of the state of the immune system and the probability of an unfavorable outcome in patients with ovarian neoplasia.

Since the middle of the previous century the heterogeneity of breast cancer became absolutely evident. This assumption was historically based on differences in clinical behavior and sensitivity to therapy. Treatment approach nowadays is based primarily on clinical and morphological prognostic and predictive markers. Among morphologically derived markers the most important are estrogen and progesterone receptors and HER2. Interestingly that tumors with expression of estrogen receptors and/or progesterone receptors that showed also hyperexpression or amplification of HER2 have very poor outcome and low sensitivity to all therapeutic approaches. Therefore we want to summarize the existing clinical information that is relevant to this topic.

Glioblastomas are the most frequent malignant neoplasm among primary brain tumors of childhood. Despite the advances in a multimodality treatment approach including neurosurgery, radiotherapy and chemotherapy, the overall survival of such patients remains poor and doesn’t exceed 14 months. The using of targeted agents such as gefitinib in unselected patient populations showed insufficient efficacy. Nowadays, the most perspective approach is a selection of patient populations potentially sensitive to targeted therapy based on predictive markers of response. We performed a comprehensive analysis of the mutational patterns in 30 glioblastomas of children. Data Analysis was based on the new method of mass spectrometry (OncoCarta v1.0, Sequenom) that enabled us to estimate 298 mutations in 19 genes and to identify 10 mutations in 9 tumors (30 %). Mutations were found in BRAF, CDK, HRAS, EGFR, FGFR, MET and PI3K. The most mutated pathway was EGFR – in 20 % of the samples (6/30). The obtained results seem to be very promising in terms of possibilities of using new targeted agents including BRAF inhibitors for treatment of children with glial brain tumors.

The article represents case studies on clinical experience of targeted therapy ribociclib in combination with letrozole in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in Russian Federation. Russian oncologists’ experience has demonstrated the high efficacy and manageable safety profile of the ribociclib treatment in patients in clinical practice.