No 41 (2015)

Rationale: Analysis of the cancer incidence and mortality in the population is of major importance for planning of measures aimed at improvement of organization of medical care to cancer patients, ensuring high quality and availability of this type of medical care.
Aim: To evaluate cancer-related incidence and mortality rates and structure among the population of the Moscow Region depending on patient gender and tumor localization.
Materials and methods: The estimation and analysis of incidence and mortality rates was performed based on the Reporting Form of the Federal Statistic Surveillance #7 “Information on disorders related to malignant tumors” in the Moscow Region in 2014. For mortality analysis, including that among pediatric patients, we used data from the State Statistics Service of the Moscow Region.
Results: In 2014, there were 25 600 new cases of malignancies diagnosed in the Moscow Region, that corresponded to the incidence rate of 363.2 per 100,000 of the population. The leading types of newly diagnosed tumors in men were prostate cancer, as well as tracheal, bronchial and lung cancers (54.2 and 47.0 per 100,000 of male population, respectively). In women, the highest incidence rates were found for breast and skin cancers (86.0 and 58.9 per 100,000 of female population, respectively). According to the data from Rosstat, in 2014, the overall cancer mortality rate in the Moscow Region was 228.1 per 100,000 of the population. Among the causes of cancer mortality in men, the leading one was tracheal, bronchial and lung cancer (22.2%), followed by stomach cancer (13.3%) and prostate cancer (8.1%). In women, the leading cause of cancer mortality was breast cancer (16.6%), followed by ovarian, uterine and cervical cancers (14.1%) and stomach cancer (11.4%).
Conclusion: Based on the results of medical and statistical analysis of cancer incidence and mortality rates, the main direction of improvement of medical care to cancer patients and the ways for further development of specialized medical care in the Moscow Region were chosen.

Background: The insulin-like growth factor (IGF) signaling system plays a major role in development and progression of various malignancies including ovarian cancer, and its components are considered as potential diagnostic and prognostic markers and the objects of molecular targeted therapy.
Aim: Comparative evaluation of IGF-I and IGF-II, and IGF-binding proteins (IGFBP)-1, 2 and 3 content in blood serum and tumors of ovarian tumor patients, analysis of their associations with key clinical pathologic characteristics of ovarian cancer and evaluation of clinical value of these markers for disease diagnostics and prognosis.
Materials and methods: IGF-I, II, IGFBP-1, 2 and 3 levels were measured with standard ELISA kits (Mediagnost, Germany) in blood serum and tumor extracts of 74 patients with ovarian cancer, 16 patients with benign and 14 with borderline ovarian tumors. The control group comprised 77 healthy women.
Results: Three potential serological markers of ovarian cancer, namely IGF-I, IGFBP-1, and IGFBP-2 were revealed. The best sensitivity to specificity ratio was demonstrated for IGFBP-2: at a 370 ng/ml cut-off level, these indices were 87 and 79%, respectively. The diagnostic markers found in our study were also associated with the prognosis of overall survival in ovarian cancer. In the multivariate analysis, low IGF-I serum levels retained its independent unfavorable prognostic value. The disease prognosis is influenced also by IGF-II and IGFBP-1 content in the tumor tissue.
Conclusion: In ovarian cancer patients, there is a disbalance of IGFs/IGFBPs. Some components of this system could be potentially used as diagnostic and prognostic markers of the disease.

Background: Neuroendocrine tumors (NET) is a heterogeneous group of neoplasms characterized by hypersecretion of biologically active sub- stances that manifests by specific syndromes and determines the clinical course of the disease. The most common NET types are those of gastrointestinal tract. The obligatory biochemical marker used in the examination of NET patients is chromogranin A (CgA).
Aim: Evaluation of the CgA value for diagnostics and monitoring of gastrointestinal NETs.
Materials and methods: A comparative study of plasma CgA levels was performed in 146 patients with gastroenteropancreatic neuroendocrine tu- mors and 66 healthy individuals using the enzyme immunoassay “Chromogranin A ELISA kit” (Dako A/S, Denmark).
Results: CgA levels were significantly higher in patients with NETs of all localizations, such as pancreas, stomach, gut, small and large bowel, than in the healthy subjects (р < 0.000001). In NET patients, CgA secretion was highly variable, with the highest value in the group of patients with gastric NETs (102000 U/l). The highest CgA medians were detected in patients with small intestinal (183.9 U/l), colon (148.4 U/l) and pancreatic (135.9 U/l) NETs. There was an association between CgA secretion and extension or activity of NETs, with the highest median values in patients with hepatic metastases (395 U/l) and those with carcinoid syndrome (352 U/l). The clinical significance of CgA as a NET marker was assessed using the cut-off value of 33 U/l, calculated according to the results in the control group. Overall diagnostic sensitivity of CgA in NET patients was high (85.8%) with a specificity of 98.5%. Conclusion: The results obtained confirm a high sensitivity of CgA as a NET marker whose determination helps to improve accuracy of diagnostics and to assess NET prevalence.

Background: The rationale for distant gamma therapy (DGT) in prostate cancer patients is the data of its effectiveness in combination with modern planner devices, as well as lower costs, compared to the use of a linear accelerator.
Aim: To access the impact of DGT based on a 3D planning software “Amphora” on the 5-year survival rate depending on the main predictors of treatment efficacy in prostate cancer patients.
Materials and methods: The study included 34 prostate cancer patients who received low-dose DGT (total focal dose of 62 to 70 Gr). Androgen deprivation was used in 73.5% of patients for 6 to 12 months.
Results: The patients with a baseline pros tate-specific antigen level < 20 ng/ml had the highest 5-year survival rate of 86%. There was no significant difference in a 5-year survival that depending on a total focal dose (< 64 Gr; ≥ 64 Gr) of DGT if used in combination with androgen deprivation. Conclusion: This data represents only the first step in establishment of the criteria to choose the type of DGT in prostate cancer patients. The optimization of a treatment strategy based on a thorough analysis of data, including that on comorbidities and their severity, would make the use of DGT more rational that will reduce costs of treatment.

Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.
Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.
Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib) and second line (nilotinib), overall survival was 100%.
Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse) or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

Background: Studies of biological effects of low dose radiation are important due to exposure of large patient groups to low radiation doses during therapeutic and diagnostic procedures. Details of biological effects of neutron irradiation have been poorly studied, including cytogenetic effects of its low doses, although they could be important during neutron therapy and for development of normatives on radiation protection with ion accelerators, including therapeutic ones.
Aim: To study patterns of structural chromosomal damage in mammalian cells exposed to 14.5 MeV neutrons at doses up to 1 Gy.
Materials and methods: Cytogenetic effect of 14.5 MeV neutrons was evaluated in human blood lymphocytes and Chinese hamster ovarian cells CHO-K1 in the dose range of 0.1–1.2 Gy, dose rate range 0.3–60 mGy/min, pulse frequency 50, 5, and 0.017 Hz. Chromosome preparations were conventionally prepared. All types of chromosomal aberrations were included into the analysis.
Results: In the 14.5 MeV neutron dose range studied, both cell cultures demonstrated the same dose-effect pattern: a drastic increase of chromosomal aberrations frequency at doses of 0.12–0.15 Gy, with a somewhat lower increase of the number of aberration in the dose range 0.3–0.5 Gy and regular linear dose dependence thereafter. This pattern was found both on the total chromosome aberrations frequency and on dicentric (lymphocytes) and paired fragments (CHO-K1) frequencies.
Conclusion: The results obtained indicate the existence of a phenomenon of hypersensitivity and induced radio-resistance in human lymphocytes and Chinese hamster ovarian cells (CHO-K1) following irradiation with 14.5 MeV neutrons.

The review describes the current views on urothelial carcinoma carcinogenesis. Based on the up-todate genetic studies, molecular pathways determining the development of superficial and invasive bladder cancers are considered. It was demonstrated that the development of noninvasive bladder tumors occurred predominantly through oncogenes activation, while the genesis of invasive cancer is based on inactivation of tumor suppressor genes. Principal mechanisms of multiple and recurrent bladder tumors development are discussed including its monoclonal and oligoclonal models.
One of the most promising nowadays approaches is the determination of new generation markers, such as molecular genetic abnormalities in the hereditary apparatus of the cell underlying its malignant transformation. Molecular markers' panels used for diagnostics, prognosis, and monitoring of urothelial carcinoma patients are analyzed.

The risk of pulmonary embolism (PE) in cancer patients  is 4–7-fold, compared to other  patient  categories. PE is the  second  most frequent  cause of death  in the first year after cancer diagnosis. PE is diagnosed in 7.5% of patients with malignant brain tumors, in 1 to 25% of those  with gastrointestinal tumors, in 4.5 to 17.5% of those with breast cancer and in 4 to 10% of lung cancer patients. The risk of PE is higher with surgical interventions and chemotherapy, as well as in metastatic tumors. In 13% of cases, PE may be the first symptom of cancer manifestation. For prevention and treatment of PE low molecular weight heparin (LMWH) and warfarin are   used. The risk of recurrent  PE is 2-fold lower with LMWH. The frequency of bleeding with LMWH and warfarin treatment is from 14 to 19%. Placement of a cava filter is indicated  only if anticoagulation is inefficient.  New oral anticoagulants,  which act as selective thrombin  or Factor Xa inhibitors, are not used in cancer patients. Thus, diagnostics and treatment of PE is a very urgent  problem in oncology that requires new approaches to be looked for.

Rationale: Orbital metastases comprise about 15% of all orbital malignancies. An orbital metastasis is to be suspected if there is a mass in the orbit of a cancer patient. Nevertheless, a non-tumor process in the orbit of cancer patients is also possible, as well as occurrence of a second cancer of the primarily multiple tumor type.
Aim: To identify characteristic signs of a metastatic tumor of the orbit to perform differential diagnosis with other tumor and non-tumor orbital disorders and to establish an algorithm for a correct diagnosis and perform an adequate treatment of an orbital disease.
Materials and methods: We retrospectively analyzed case histories of 81 patients with malignant tumors of various organs and an orbit abnormality. Seventy four (74) of them had orbital metastases (64 women and 10 men aged from 18 to 87 years; median age, 45 years); the second malignant orbital tumor was represented by a non-Hodgkin's lymphoma in 5 patients (4 women and 1 men aged from 55 to 78 years, median age 61 year). Two men of 64 and 66 years had orbital inflammation imitating a metastatic tumor. In addition to ophthalmological assessment and orbital CT, assessment of visceral organs and systems was performed in all patients to exclude any relapse of primary tumors and metastases in other organs.
Results: The most prevalent among orbital metastases was a focal form of the tumor growth adjacent to the orbital wall (mainly, the upper one), with gradual development of a non-painful exophthalmos and abnormalities of eye movements. The same clinical manifestation was typical also for a non-Hodgkin's lymphoma of the orbit. An acute inflammation of orbital tissues in cancer patients did not have a clear clinical manifestation and simulated an orbital metastasis.
Conclusion: For a nearly diagnosis of orbital metastasis it is necessary to perform a combined analysis of past history, clinical manifestation and results of morphological assessment of a tumor biopsy sample.