Renal cell carcinoma is one of the most common diseases in oncourology. The leading morphological variation of renal cell carcinoma today is the light-cell subtype, which is determined in 80% of cases. Despite the intensity of diagnostic methods, almost 1/3 of patients with kidney cancer have distant metastases during initial examination, which causes extremely high mortality rates from this oncopathology. Standard chemotherapy schemes with the inclusion of fluoropyrimidines and antitumor antibiotics, cytokine therapy using interleukin-2 and interferon α only slightly prolonged the life of patients, while causing pronounced toxic-anemic adverse events. The appearance of tyrosine kinase inhibitors has allowed us to obtain really significant results in the treatment of metastatic renal cell carcinoma. The next step in the treatment of renal cell carcinoma was the registration by the US FDA in April 2018 of a combination of immuno-oncological drugs ipilimumab and nivolumab for the treatment of metastatic renal cell carcinoma. Afterwards, combinations of immune checkpoint inhibitors with targeted drugs were registered, which not only significantly increased the life expectancy of patients, but also reduced the incidence of adverse events of antitumor therapy. This article provides clinical examples demonstrating the effectiveness of the combination of pembrolizumab and axitinib in the treatment of patients with metastatic renal cell carcinoma.

ЦЕЛЬ ИССЛЕДОВАНИЯ Изучение клинических характеристик костных метастазов рака легкого и эффективности паллиативной лучевой терапии. МАТЕРИАЛ И МЕТОДЫ В исследовании, состоявшем из 3 этапов, проанализировано 819 случаев лечения больных с метастазами в скелете различной первичной локализации. Представлен 71 (8,7%) больной с метастазами в скелете рака легкого. Эффективность лечения оценивали по частоте полного общего обезболивающего эффекта, относительной редукции болевого синдрома и частоте рецидивов боли. Протокол исследования предусматривал использование суммарной очаговой дозы от 13 до 26 Гр за 2—4 фракции по 6,5 Гр. РЕЗУЛЬТАТЫ Средняя длительность наблюдения составила 5,3 мес (1—30 мес). В большинстве случаев выявляли метастазы в позвоночнике — 32 (45,1%), поражение костей таза отмечено в 14 (19,7%) случаях, длинных трубчатых костей — в 11 (15,5%). Исходная интенсивность болевого синдрома при раке легкого была достоверно выше, а относительная редукция боли — ниже по сравнению с таковыми при метастазах рака молочной железы (p<0,01), на границе достоверности оказалась низкая вероятность достижения полного обезболивания (p=0,06). Достоверных различий в эффективности лучевой терапии в зависимости от морфологии опухоли выявлено не было (p=0,36). Однако обращает на себя внимание более высокая частота полного обезболивающего эффекта в случае костных метастазов аденокарциномы по сравнению с плоскоклеточным раком (50 против 18,2%). Вероятность прожить без прогрессирования болевого синдрома в течение 6 и 12 мес составила 70%, а вероятность полного обезболивания в те же сроки — соответственно 40 и 34%. ЗАКЛЮЧЕНИЕ Исходя из полученных данных, метастазы в скелете рака легкого следует относить к относительно радиорезистентным поражениям с вероятностью достижения полного обезболивающего эффекта менее чем в половине случаев. При этом высокая общая эффективность облучения в дозе 26 Гр за 4 фракции по 6,5 Гр и хорошая переносимость лечения позволяют считать данную методику лучевой терапии оптимальным вариантом для использования в клинической практике.

Hereditary breast cancer (BC) accounts for about 5-10% of cases. BRCA-associated tumors have been identified as a separate group of malignant neoplasms with distinctive clinical manifestations and specific treatment features. Understanding of biological mechanisms leading to cancer in BRCA1/2 mutation carriers and discovery of potential molecular targets, such as poly (ADP-ribose) polymerase (PARP), involved in base excision repair mechanisms, led to the development of a new class of targeted drugs belonging to the PARP inhibitors group. PARP inhibition leads to the preservation of single-stranded DNA breaks, the arrest of the replication fork, and the realization of the “synthetic lethality” phenomenon due to the inability to repair double-stranded DNA breaks by homologous recombination in cells with mutations in the BRCA1/2 genes. Two randomized trials OlympiAD and EMBRACA evaluated and proved the effectiveness of PARP inhibitors in patients with metastatic BRCA-mutated HER2-negative breast cancer in comparison with standard chemotherapy. At the same time, data on the potential use of PARP inhibitors for the treatment of BRCA-mutated HER2-positive breast cancer patients are extremely limited. This article presents a clinical example of the use of olaparib in a patient with BRCA-mutated HER2-positive metastatic breast cancer.

Cholangiocarcinoma includes a highly heterogeneous group of malignant tumors of the biliary tract, developing from the epithelium of the intra- and extrahepatic bile ducts. The incidence of cholangiocarcinoma is growing worldwide and currently accounts for about 15% of all primary neoplastic diseases of the liver and up to 3% of malignant neoplasms of the gastrointestinal tract. The asymptomatic course of these tumors in combination with a very aggressive course and low sensitivity to cytotoxic therapy contributes to a fairly high mortality rate from this disease, amounting to up to 2% in the structure of cancer mortality in the world. The high heterogeneity of cholangiocarcinoma at the genomic, epigenetic and molecular levels significantly reduces the effectiveness of the available treatments. In recent decades, new diagnostic tools and treatment methods have been developed to improve the results of treatment of patients with cholangiocarcinoma. The prevalence of BRAF gene mutations is associated with the occurrence of various tumors, including cholangiocarcinoma. Currently, more than 30 mutations in the BRAF gene with oncogenic potential have been registered. Basically, the V600 codon is affected, an amino acid change occurs, which ultimately leads to the fact that the BRAF protein becomes constantly active, even in the absence of growth factors. Dabrafenib is an inhibitor of the BRAF protein, which is permanently overactive in mutated cells. The use of dabrafenib as monotherapy leads to the development of resistance after 6–7 months. Dabrafenib is used with trametinib, a MEK inhibitor that also blocks the Ras-Raf-MEK-MAPK kinase pathway, to prevent the resistance.

Prostate cancer is one of the most common neoplasms in men. It currently ranks second in Russian Federation amongst male population in overall number of cases after only lung cancer and third in cancer mortality. Prostate cancer is rarely diagnosed in patients younger than 40 years old, with overage age of diagnosis being between 50 and 70 years. A lot of different new treatment options were developed in the last decade for patients with metastatic prostate cancer (mPC). Despite androgen-deprivation remaining the standard of therapy, it has been proven that the addition of cytotoxic and hormonal drugs of new generation improves overall survival of patients with castration-sensitive and castration-resistant metastatic disease. Recently, enzalutamide became the new standard of care not only in castration-resistant mPC, but also in the setting of metastatic castration-sensitive prostate cancer, due to the data acquired in two large randomized trials ARCHES and ENZAMET. This article provides clinical examples demonstrating the effectiveness of enzalutamide in various forms of prostate cancer. In the first clinical case enzalutamide was used in the treatment of castration-sensitive mPC. Currently, patient continues to receive this therapy with progression-free interval exceeding 11 months. In the second clinical case, enzalutamide has shown its efficacy in the setting of castration-resistant PC. Stable disease was achieved and as of right now patient has shown no signs of progression for 9 months, which is already a significantly better result in comparison with previous lines of treatment.

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 <3 vs ≥3 lines of therapy for metastatic disease in the anamnesis was 9 months vs 4 months, respectively (HR = 4,216; 95% CI [1,334–13,327]; p = 0.0056). In the presence or absence of platinum-containing agents in previous lines of therapy 5 months vs 9.5 months, respectively (HR =1.484; 95% CI [0.48–4.582]; p = 0.4750).During the treatment with talazoparib adverse events of the 3rd-4th grades were observed in 5 patients (20,8%). These include moderate and severe anemia in 3 patients (12.5%), thrombocytopenia in 1 patient (4%), and neutropenia in 1 patient (4%). The majority of patients (79,5%), which received talazoparib, did not require dose adjustment. The need to reduce the dose to 0.75 mg was noted in 3 patients (12.5%), to 0.5 mg – in 2 patients (8%). Hemotransfusion was performed in 3 patients. For effective therapy safety management regular monitoring of blood parameters is necessary.Conclusion. Thus, targeted therapy with talazoparib is an effective treatment option for HER2-gBRCA+ mBC.

Although many currently known molecular targets are characterized by organ specificity, they can be found in various types of tumors. Molecular diagnostic techniques can be used to help select patients who are most likely to benefit from target therapy. Case presentation. We describe the case of a 38-year-old patient with advanced gastric cancer with peritoneal dissemination. On december 11, 2014, the patient underwent palliative subtotal gastrectomy followed by 18 cycles of chemotherapy (xelOx) and radiotherapy. On February 2, 2017, percutaneous transhepatic cholangiostomy of the left lobe bile duct was performed. in May 2017, the stent was inserted into the common bile duct due to bile duct stenosis. three months later, disease progression (multiple liver metastases) occurred, and chemotherapy with paclitaxel was given in a weekly schedule. therapy with crizotinib was administered 3 months after determining the alK mutation. the duration of treatment was 8 months with satisfactory tolerability. Conclusion. target therapy with krizotinib seems to be an effective treatment for alK-positive tumors.

Anaplastic thyroid cancer is one of the most aggressive and fatal human carcinomas. A significant experience in using various kinase inhibitors for anaplastic thyroid cancer therapy has been accumulated worldwide. The most encouraging results were obtained after using a combination of b-Raf and MEK kinase inhibitors (vemurafenib/dabrafenib and trametinib/cobimetinib, respectively) for the treatment of the unresectable BRAF V600E -positive anaplastic thyroid cancer. This drug combination makes it possible to perform surgery followed by chemoradiotherapy and other targeted therapies. Here we report a clinical case of anaplastic thyroid cancer in a 69-year-old woman, who was treated with neoadjuvant targeted therapy. The treatment was carried out on the basis of three medical institutions: the National Medical Research Radiological Centre (Moscow), the N.I. Pirogov Clinic of Advanced Medical Technologies (St. Petersburg) and the Endocrinology Research Center (Moscow). Since there is still no universal protocol for treating ATC patients, and only palliative therapy is used in most cases, we emphasized on diagnostic and treatment errors of this disease. Special attention was paid to the importance of using molecular diagnostics and modern medical imaging technologies.

Testicular cancer is a rare malignant tumor. In the structure of general cancer incidence, this nosology accounts for about 1–1.5% of cases. Among this pathology, about 90–95% is due to testicular germ cell tumors. Currently, testicular cancer is a potentially treatable solid tumor with a 10-year survival rate of more than 95% upon timely diagnosis and proper treatment. In this regard, early diagnosis and treatment of this pathology is an urgent task today. The article presents a clinical observation of the treatment of a patient with a testicular germ cell tumor. The presented clinical case demonstrates the successful conduct of neoadjuvant chemotherapy and further orchifuniculectomy in the presence of distant metastases namely in case of a non-seminomic form of a testicular germ cell tumor. The approach to treating patients with testicular tumors must be individualized and take into account both the potential gain and the potential risks of the treatment being performed.

The treatment of common forms of squamous cell carcinoma of the organs located on the head and neck that are not subject to surgical treatment is limited to the use of chemoradiotherapy with platinum derivatives or drug therapy with platinum-containing regimens. With the progression of the disease, ineffective 2‑line cytostatics were prescribed that did not fundamentally change the course of the tumor process. The introduction into clinical practice of drugs of the original mechanism of action has significantly increased the effectiveness of drug therapy during progression after platinum-containing chemotherapy. The article presents two clinical observations that demonstrate the relevance of the strategy of using inhibitors of immune response control points after platinum preparations.

Today, understanding the molecular mechanisms involved in the activation of signaling pathways that initiate intracellular proliferation, adhesion, invasion, and angiogenesis has led to the design and widespread clinical introduction of targeted drugs that enhance the efficiency of treatment and minimize its toxicity for other organs and tissues. The possibility of using targeted therapy is assuming a particular importance in previously treated patients. The present-day experience with Regorafenib allows the latter to be considered as an effective agent in the treatment of patients with advanced colorectal cancer.

Testicular cancer is a rare malignant tumor. In the structure of general cancer incidence, this nosology accounts for about 1–1.5% of cases. Among this pathology, about 90–95% is due to testicular germ cell tumors. Currently, testicular cancer is a potentially treatable solid tumor with a 10-year survival rate of more than 95% upon timely diagnosis and proper treatment. In this regard, early diagnosis and treatment of this pathology is an urgent task today. The article presents a clinical observation of the treatment of a patient with a testicular germ cell tumor. The presented clinical case demonstrates the successful conduct of neoadjuvant chemotherapy and further orchifuniculectomy in the presence of distant metastases namely in case of a non-seminomic form of a testicular germ cell tumor. The approach to treating patients with testicular tumors must be individualized and take into account both the potential gain and the potential risks of the treatment being performed.

Prostate cancer (PC) is now one of the most common malignancies among men. Radical prostatectomy is the most commonly used therapy option for patients with localized PC. The appropriateness of surgical treatment for locally advanced and lymphogenic metastatic PC remains controversial, as the probability of non-radical intervention increases significantly and the risk for disease progression becomes higher. At the same time, interest in surgical treatment in patients with PC at high risk of progression, including those with lymphogenic metastases has recently increased greatly. There are more and more studies demonstrating improved survival rates in patients with high-risk PC, including those with distant metastases, who have undergone radical prostatectomy and lymphadenectomy compared with a cohort of patients who have received only drug therapy In addition to the studies evaluating the efficiency of neoadjuvant therapy before surgery in patients with localized or locally advanced high-risk PC, there are also investigations considering this option in PC patients with lymphogenic metastases. The paper gives the results of a clinical observation that shows the high efficiency of a multimodal approach with neoadjuvant chemohormonal therapy, followed by surgical treatment in a patient with lymphogenic metastatic PC.

Objective: to assess safety, responses rate and duration, progression-free and overall survival in patients with advanced urothelial carcinoma receiving vinflunine as second-line therapy in routine clinical practice, after additional patient recruitment.Materials and methods. This retrospective observational multicenter study included medical data of 34 patients with verified advanced urothelial carcinoma receiving vinflunine for tumor progression after first-line chemotherapy in 11 Russian clinical centers from March 23, 2013 to June 3, 2017. The median age of the patients was 60 (44–81) years. ECOG performance status was 0 in 2 (5.9 %), ECOG 1 – in 21 (61.7 %), ECOG 2 – in 9 (26.5 %), and ECOG 3 – in 2 (5.9 %) patients. Visceral metastases were present in 14 (41.2 %), non-visceral – in 20 (58.8 %) cases. Anemia was recorded in 20 (58.8 %) patients. According to Bellmunt scale 2 (5.9 %) patients had none risk factors, 6 (17.6 %) had 1 risk factor, 18 (52.9 %) and 8 (23.5 %) had 2 and 3 risk factors, respectively. Initial vinflunine dosage was 320 mg/m2 in 6 (17.6 %) patients, 280 mg/m2 in 22 (64.8 %) or 250 mg/m2 in 6 (17.6 %). Patient received a median of 4 (1–10) cycles of therapy.Results. Adverse events (AE) were recorded in 33 (97.1 %) cases. The most frequent were general (70.6 %), hematologic (58.8 %), and gastrointestinal AE (41.1 %). Most AE were grades I–II and well-controlled. There were no deaths caused by adverse events. The best response was assessed as complete in 1 (2.9 %), partial – in 5 (14.7 %), stabilization – in 19 (55.9 %), and progression – in 9 (26.5 %) of the 34 patients. Complete response duration was 9.0 months, median partial response duration was 8.0 months (95 % confidence interval (CI) 5.5–13.0); median stabilization duration – 3.5 months (95 % CI 0.7–12.8). Median progression-free and overall survival were 3.9 (95 % CI 3.5‒4.3) and 6.4 (95 % CI 0.1–17.0) months, respectively. Univariate analysis indicated that the low somatic ECOG status and the initial vinflunine dosage of 250 mg/m2 had adverse impact on overall survival.Conclusion. The efficacy and safety of vinflunine as second-line therapy for first-line chemotherapy-resistant advanced urothelial carcinoma in unselected patients are similar to the results of Phase III randomized trial and early results of the Russian observational study.