Vol 21, No 2 (2019)


Lung cancer in the Tomsk region (epidemiological aspects)

Choynzonov E.L., Zhuikova L.D., Ananina O.A., Odintsova I.N., Pikalova L.V.


Aim. To study the incidence and mortality of lung cancer (LC) in the Tomsk region and to assess the economic damage. Materials and methods. The population-based cancer registry data collected at Tomsk Regional Cancer Center and the Federal State Statistics for 2007-2017 were used. The extensive, intensive and standardized variables were analyzed. Results. LC was the 4-th most common cancer, comprising 10.4% (10.1% in the RF) of all cancer cases in the Tomsk region in 2017. It ranked as the first most prevalent cancer for men (17.0%) and the 6-th for women (4.7%). The LC incidence rate decreased by 19.6%, reaching 29.5±1.3 per 100 000 (р=0.0149). It decreased in men (р=0.0006) but was stable in women. In 2017, the lifetime risk of cancer was higher in the Tomsk region than that in the RF, being 7.3% for men and 1.5% for women. LC was the most common cause of mortality from cancer for both sexes (18.9%), being the most common in men (28.1%) and the 4-th most common in women (8.0%). The mortality rate was higher in men than in women (55.6 versus 6.0; р=0.0012). In 2016, the total loss of the life potential in men amounted to 8.4 thousand, for women - 2.5 thousand man-years. Economic damage in the form of conditionally non-produced national income was growing and in 2016 amounted to 263.7 million rubles. Conclusion. Epidemiological analysis of LC in the Tomsk region indicates the relevance of improving the anticancer struggle with the development and implementation of ideas aimed at increasing the cancer literacy of the population and the alertness of primary care physicians, the formation and monitoring of risk groups, the timely routing of patients with suspected cancer.
Journal of Modern Oncology. 2019;21(2):6-9
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Unresectable hepatocellular carcinoma: new opportunities and prospects for therapy

Abdurakhmanov D.T., Breder V.V., Bolotina L.V., Kosyrev V.I., Medvedeva B.M., Petkau V.V.


Hepatocellular carcinoma (HCC) is the most common liver malignancy and ranks sixth for cancer prevalence and fourth place among the causes of cancer mortality. Despite the improvement of diagnostic techniques, the diagnosis of HCC is still determined in the late stages. The absence of screening programs in groups of risk of HCC (cirrhosis) and the late diagnosis of HCC show the mortality rate exceeds incidence rate in the Russian Federation. It is important to improve the diagnostic methods for early detection of HCC and to use the multidisciplinary approach in diagnosis and treatment of HCC in association with different specialists (hepatologist, oncologist, chemotherapist, surgeon, transplantologist, interventional radiologist). Systemic therapy should be used in all patients with unresectable HCC and compensated liver function. Since 2007 sorafenib has represented the only approved drug for treatment of unresectable HCC. In 2017, according to the results of REFLECT trial lenvatinib was registered for the treatment of unresectable HCC in the first line therapy. For the first time in the last 10 years the efficiency of lenvatinib application in comparison with sorafenib was practically the same, concerning the overall survival rate. Lenvatinib also demonstrated the statistically significant and clinically meaningful benefit in terms of improvement of survival without progression, the time to progression and frequency of objective response rate compared with sorafenib.
Journal of Modern Oncology. 2019;21(2):10-16
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The potential of using eribulin in patients with breast cancer, associated with brain metastasis: the scientific background and the Russian clinical experience

Kolyadina I.V., Bulavina I.S., Petkau V.V., Strakhova N.V., Gorbunova V.A., Kovalenko E.I., Manziuk L.V., Artamonova E.V., Zhukova L.G., Bolotina L.V., Gan'shina I.P., Semiglazova T.I., Manikhas A.G., Raevskaia N.A., Itkin I.M., Khokhlova S.V., Filonenko D.V., Gol'dberg V.E., Popova N.O., Ponomarenko D.M., Shikina V.E., Vladimirova L.I., Tikhanovskaia N.M., Karabina E.V., Mukhametshina G.Z., Khasanova A.I., Safina S.Z., Shaidorov M.V., Orlov A.E., Kostalanova I.V., Levchenko N.V., Osipov M.A., Karandeeva T.V., Evstigneeva I.V., Chernov I.S., Kolokolov D.D., Povyshev A.I., Shatokhina A.S., Cherniakova E.M., Shkodenko O.N., Kuz'mina E.S.


Aim. Eribulin is an active cytostatic, associated with a wide range of mechanisms of antitumor effects, but eribulin efficiency and safety in patients with breast cancer (BC), associated with cerebral metastases are still poorly understood. Materials and methods. We analyzed the combined Russian experience of eribulin application in BC patients associated with brain metastases; the analysis included 459 Russian women with advanced BC who had received at least 2 course of eribulin during the period from 2014 to 2018; 35 of 459 patients had brain metastases (40.0% - luminal HER2-negative subtype, 31.4% - triple negative subtype and 28.6%h - HER2-positive BC). The median age was 52 years (39 - 80 years of age). In most cases, the patient had two or more metastatic brain lesions (68.6%; the median was - 3); brain radiotherapy was used in 62.8% of patients before eribulin treatment and in 5.8% of patients was held stereotactic radiation therapy during eribulin chemotherapy. We analyzed the efficiency of eribulin application (the therapy continued until disease progression, the development of unacceptable toxicity, or impossibility to apply the drug for any other reason). Results. The results showed that clinical efficacy (objective response rate + stabilization of disease lasting for more than 6 months) was 48.6%: partial response - in 20% of patients and stabilization of disease - 62.9%; tumor growth control was in 82.9%. Median PFS in all group of patients with brain metastases was 4.1 months and was similar to median PFS in patients who received radiotherapy before eribulin treatment or without eribulin - 4.1 vs 3.47 months; p=0.798. Conclusions. The application of eribulin in BC patients with brain metastasis are absolutely justified, the drug demonstrates the efficiency in a retrospective analysis in a Russian population. The determination of the optimal algorithm for the treatment of patients with metastatic BC associated with brain metastasis requires a multidisciplinary approach and further research.
Journal of Modern Oncology. 2019;21(2):17-24
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Successful experience of combined immunochemotherapy at refractory course of primary cutaneous peripheral T-cell lymphoma, unspecified

Gorenkova L.G., Kravchenko S.K., Belousova I.E., Babicheva L.G., Kalashnikova D.D., Poddubnaya I.V.


Primary cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of T-cell lymphoproliferative diseases that involve mainly the skin and are characterized by features of their diagnosis, clinical course and therapeutic approach. They include mainly fungal mycosis and CD30 + lymphoproliferative skin diseases (primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis) which account for >50% of CTCL and primary cutaneous peripheral T-cell lymphoma, unspecified/ /not otherwise specified (PTL NOS) which occurs extremely rare. Activation antigen CD30 is a cell membrane glycoprotein that belongs to tumor necrosis factor (TNF) superfamily. Tumor cells in primary skin CD30-positive skin lymphomas express CD30 in more than 75%; in other nosological units it also can be detected but to a lesser extent. Most patients with cutaneous CD30 + lymphoproliferative diseases have an indolent the disease course of the disease with a favorable prognosis. Refractory course occurs in approximately 30% patients, and in 8% of cases lymphoma results in deaths. Recently monoclonal antibodies have been included in clinical practice for the treatment of T-cell lymphomas, one of which is brentuximab vedotin, a CD30 monoclonal antibody conjugated to monomethyl auristatin E. This article provides the clinical case of a patient with a refractory form of PTL NOS.
Journal of Modern Oncology. 2019;21(2):25-28
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The cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab

Rudakova A.V., Strugov V.V.


Background. Current treatment of relapsed/refractory chronic lymphocytic leukemia implies the use of regimens that include innovative drugs such as ibrutinib and a combination of venetoclax with rituximab. Herewith the combination of venetoclax with rituximab provides a high rate of eradication of minimal residual disease and, in contrast to ibrutinib, in the standard version it is canceled after 2 years from the start of therapy. Aim. Evaluation of the cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax + rituximab and ibrutinib. Materials and methods. The evaluation was carried out from a position of the health care system using the Markov model. The study’s time horizon was 4 years. There were no statistically significant differences in overall and progression-free survival according to data of an indirect comparison of the study MURANO for the combination of venetoclax + rituximab and the studies RESONATE and HELIOS for ibrutinib. Venetoclax price (excluding VAT) used for calculation was corresponded to the manufacturer's price list and it was: film coated tablets, 10 mg №14 - 5830.2 rubles; 50 mg №7 - 14 576.86 rubles; 100 mg №7 - 29 152.65 rubles; 100 mg №14 - 58 306.37 rubles; 100 mg №112 - 466 446.67 rubles. Prices for rituximab and ibrutinib were corresponded to a median of the prices quoted. In all cases the analysis considered VAT and weighted average wholesale surcharge given population size in the Russian Federation. In the base case, costs of therapy after a transition to progression were not considered. When carrying out the sensitivity analysis, the option of monotherapy with venetoclax in patients who had progression on ibrutinib and monotherapy with ibrutinib in patients who had progression on venetoclax + rituximab was also evaluated. As part of the sensitivity analysis, a decrease and increase in the price of venetoclax by 15% and a decrease in the price of ibrutinib by 30% were also evaluated. In addition, an increase in a proportion of patients who moved to progression followed venetoclax withdrawal after 2 years of therapy was evaluated, by 15% per year, as well as a change in a frequency of progression by 15% compared with the base case and a decrease in the study’s time horizon to 3 years. The analysis was performed with discounting at 3.5% per year. Results. The analysis showed that the use of a regimen that includes venetoclax reduces the cost volume by on average of 31.3% compared to ibrutinib (the cost volume for 1 patient per 4 years - 13.341 million rubles and 19.413 million rubles, respectively). The sensitivity analysis demonstrated a reliability of the data obtained (with all analyzed modeling options, including options with an increase in venetoclax price by 15%, a decrease in ibrutinib price by 30% and a decrease in the study’s time horizon to 3 years, the combination of venetoclax + rituximab reduces costs by 1.9-41.0%). Conclusions. Treatment of relapsed / refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab is comparable in clinical efficacy with ibrutinib monotherapy and can reduce the cost and, therefore, increase the availability of innovative therapy for this group of patients. The main contribution to cost reduction is made by the fact that treatment with venetoclax and rituximab in the absence of progression stops 2 years after the start of treatment, and is not performed until the response is lost, as in the case of ibrutinib.
Journal of Modern Oncology. 2019;21(2):29-32
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The use of regorafenib in colorectal cancer

Sekacheva M.I., Bagmet N.N., Guryanova A.A., Rashi D.A.


Colorectal cancer is the third most common type of cancer in men and the second in women worldwide. The data demonstrate the increase in the annual incidence of colorectal cancer, but still the significant number of patients is detected having late-stage cancer. Regorafenib is an oral multi-kinase inhibitor that targets kinases VEGF1, VEGF2, VEGF3, PDGFR, and FGFR involved in the regulation of tumor angiogenesis, and KIT, RET, RAF-1, BRAF involved in oncogenesis. The application of regorafenib has shown statistically significant increase of progression-free survival and overall survival, thus regorafenib been approved for the treatment of metastatic colorectal cancer, associated with resistance to fluoropyrimidine, oxaliplatin or irinotecan-based therapy in combination with the VEGR inhibitor and anti-EGFR-antibodies in patients with wild type KRAS gene. The article deals with the results of major studies carried out to explore the characteristics and efficacy and safety evaluation of regorafenib. We have analyzed in the review the results of recent studies on changes in indicators of overall survival, progression-free survival, and the efficacy of regorafenib therapy, safety and objective response.
Journal of Modern Oncology. 2019;21(2):33-36
pages 33-36 views

Management of the patients with stage I germ cell ovarian tumors

Nechushkina I.V., Nechushkina V.M., Boychenko E.I., Susuleva N.A.


The goal of the treatment of children and adolescents with germ cell ovarian tumors is to save both life and its quality. One of the quality of life issue in pediatric patients is fertility preservation. The removal of the ovary on the affected side allows saving the ovary on the opposite side. The single ovary is able to save further full development of female secondary sexual characteristics and will play important role as psychological value. In addition, the reproductive function will be stored. Chemotherapy may badly impact the function of a single ovary. To find out in advance how chemotherapy will affect ovarian function is impossible, so it is necessary for patients with Stage I ovarian germ cell tumors to decide the possibility of dismissing chemotherapy from the treatment. Under certain conditions unilateral salpingo-oophorectomy may be sufficient for stage I disease. Risk factors which should be considered when refusing chemotherapy are discussed.
Journal of Modern Oncology. 2019;21(2):37-39
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Modern ultrasound diagnostics for locally advanced cervical cancer

Ovodenko D.L., Khabas G.N., Makarova A.S., Pirogova M.S., Seregin A.A., Golitsyna Y.S., Ashrafyan L.A.


Aim. To determine the diagnostic characteristics of ultrasound when evaluating the response to neoadjuvant chemotherapy in patients with locally advanced cervical cancer. This assessment is very important and necessary to define further treatment policy. Materials and methods. The survey data of 142 patients with locally advanced cervical cancer of stages IB2-IIIB, who underwent neoadjuvant chemotherapy at the first stage of complex treatment, was analyzed. Evaluation of the effectiveness of treatment was carried out using clinical methods of research, as well as a comprehensive ultrasound. Complex ultrasound study was conducted before treatment initiation and after each chemotherapy cycle. Results. After neoadjuvant chemotherapy in patients with locally advanced cervical cancer, the volume of the primary focus, as determined by clinical examination and ultrasound (B-mode), decreased by more than 50%. Doppler ultrasound revealed a significant decrease in the velocity parameters of blood flow in the uterine arteries and the cervical stroma. Radical surgery after chemotherapy was performed in 133 (93.7%) cases. Conclusions. Dynamic ultrasound monitoring is quite informative when assessing the effectiveness of neoadjuvant chemotherapy in patients with locally advanced cervical cancer. The main ultrasound response criteria for treatment is the dynamics of the tumor volume, as well as functional parameters of blood flow in the tumor tissue.
Journal of Modern Oncology. 2019;21(2):40-45
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Relevance of endosonography in diagnosis of tumor and pretumor pathology of the larynx, oropharynx and laryngopharynx

Allakhverdieva G.F., Sinyukova G.T., Malikhova O.A., Tumanian A.O., Cherkes L.V., Gudilina E.A., Danzanova T.Y., Opekunova V.V.


Aim. The study objective is studying the possibility of endosonography in the diagnosis of tumor and pretumor pathology of the larynx, oropharynx and laryngopharynx. Materials and methods. Endosonographic study was conducted in 20 patients with tumors and suspected tumors of the larynx, laryngopharynx and oropharynx. Results. The use of endoscopic ultrasound (EUS) method was useful and important in determining the thickness and structure of the tumor, with hyperplasia of the lingual and palatine tonsils. Endosonographic picture of fibrous changes after surgery and post-radiation changes, lack of blood flow in the fibrous tissue and blurred contours gave additional information in the differential diagnosis of tumor and non-tumor changes. The results of the ultrasound examination performed in the standard B-mode for the presence of tumors, cysts and formations, suspicious of the tumor of the submucosal layer of the oropharynx and larynx, which were not determined by endoscopic examination, were confirmed. Conclusion. Obtaining a sonographic image simultaneously with endoscopic examination of the formations in the submucosal layer of the oropharynx and larynx will shorten the diagnostic algorithm of the study in patients with pathological changes in this area. The use of endosonography made it possible to confirm the data obtained by ultrasound examination in B-mode and which were not confirmed by endoscopic examination.
Journal of Modern Oncology. 2019;21(2):46-50
pages 46-50 views

Effective use of the endoscopic vacuum system in the comprehensive treatment of a patient with a defect in the abdominal segment of the esophagus after gastrectomy

Abu-Khaidar O.B., Vodoleev A.S., Pirogov S.S., Khomiakov V.M., Riabov A.B.


In oncosurgery esophago-intestinal anastomotic leak as well as defects of the abdominal segment of the esophagus are serious complications associated with prolonged hospital stay and increased mortality rate. A choice of management tactics for each patient is individual. Treatment of esophageal anastomotic leak without separation provides the best result by reducing the time of rehabilitation, improving the quality of life and reducing mortality. Conservative treatment requires an adequate drainage when conducting enteral feeding and adequate antibiotic therapy. The indications for separation of the anastomosis include a large defect size, necrosis of the graft uncontrolled purulent-septic complications and a failure of conservative therapy. In recent decades a number of methods for endoscopic treatment of anastomotic leaks in the gastrointestinal tract have been elaborated, including the use of adhesive agents, self-expanding stents, clipping, and endoscopic vacuum system. These methods have several advantages over surgical and conservative management. Despite the accumulated experience, at present there is no single systemic approach to the use of endoscopic methods for closure of defects of anastomosis as well as defects of the abdominal segment of the esophagus. This is mainly due to a relatively small number of publications. One of the promising methods for endoscopic treatment of anastomotic leak is currently the Endoscopic Vacuum System (EndoVAC therapy). The article provides the clinical case of a patient with stomach cancer who was given transperitoneal gastrectomy with D2-lymphadenectomy which was complicated by a defect in the abdominal segment of the esophagus with peritonitis. To treat those complications relaparotomy, sanitation and drainage of the abdominal cavity was performed. In order to achieve closure of the fistula more quickly the vacuum system was used resulting in a marked decrease in fluid exudation, which in turn contributed to closure of the fistula.
Journal of Modern Oncology. 2019;21(2):51-54
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Quality of life and psychological status of thoracic and abdominal pediatric cancer survivors

Mikhailova S.N., Sachuk O.V., Sukhanovskaya E.N., Valiev T.T., Kazantsev A.P., Rubanskaya M.V., Pimenov R.I., Malakhova A.A., Babij E.S.


Relevance. The integrated approach in the treatment of malignant tumors in the chest or abdomen combined with achievements of surgery, chemotherapy and accompanying therapy significantly increased survival rate and recovery in paediatric patients and then specialists faced the new challenge - to improve indicators of the quality of life (QOL) in cured patients. The aim. To study indicators of the QOL and psychological characteristics of personality development in patients cured in childhood of tumors in the chest or abdomen. Materials and methods. The study included 184 patient aged between 8 and 18 years, cured of tumors in the chest or abdomen in RAMS N.N.Blokhin RCRC Pediatric Oncology and Hematology Research Institute of Ministry of Health of Russia from 1979 to 2015. The follow-up period was 3-25 years after the end of the complex antitumor treatment. The QOL analysis was held in 92 (50%) of patients. The QOL analysis was performed according to the examining children’s questioning in the PedsQL questionary. In addition, we assessed the psychological state and social adaptation measures in patients cured of tumors in the chest or abdomen. Results. The analysis demonstrated the reduction of the indicators of the QOL and psychosocial adaptation in patients cured of tumors in the chest or abdomen. Most often the reduction of adaptation occurred in adolescents (78%). We marked the increase in the frequency of medical care encounters of non-oncological profile, the decrease in cognitive function, hypererethism, indecisiveness and low self-confidence. Conclusions. We showed guidelines for the individual rehabilitation of patients cured of tumors in the chest or abdomen: sanatorium resort therapy, psychocorrective work, psychological rehabilitation for family of the patient.
Journal of Modern Oncology. 2019;21(2):55-60
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Laser irradiation of blood as a method of prevention of oral mucositis

Gusev L.I., Pritiko D.A., Lukash E.N., Ivanova N.M., Sergeenko E.Y.


Aim. Study the effectiveness of oral mucositis (OM) prevention by the stimulation of white cells phagocytic activity and activation of endogenous keratinocyte growth factor production by laser blood irradiation method (LBI). Materials and methods. This study covers 44 patients with malignant tumors. 29 patients have already passed the high-dose polychemotherapy complicated by OM development. 15 patients have not passed the high-dose polychemotherapy yet before this admission. In the study we applied the method of identification of the white cells phagocytic activity state using the test sheet of latex microparticles. The study was performed before high-dose polychemotherapy, after LBI and after chemotherapy. Blood exposure to laser irradiation was made by placing the emitter on skin above the large vessels: areas of carotid arteries and veins, cubital, subclavian or popliteal. Results. LBI technique was used in 92 courses of high-dose polychemotherapy. Stimulation of phagocytes by LBI method showed that application of this method before chemotherapy leads to the positive result in all cases. All children (n=44), that were subject to white cells phagocytic activity stimulation, had not OM. Conclusion. Blood test for white cells phagocytic activity gives a chance to determine the actual readiness of the body to resist infections. If it was impossible to predict oral mucositis development before, now implementation of white cells phagocytic activity determination method improves the effectiveness of such prognosis. Thus, first in the world, all results that we obtained became possible only due to implementation of the white cells phagocytic activity test and stimulation of the white cells phagocytic activity and activation of the endogenous keratinocyte growth factor production by laser blood irradiation method.
Journal of Modern Oncology. 2019;21(2):62-67
pages 62-67 views

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