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Gynecologic Oncology

Gynecologic Oncology 2020 #2

Content

FUNDAMENTAL ONCOLOGY
Shakiba Ya., Volskaya М.А., Tikhonova О.А., Vorobyov P.О., Lipatova А.V
Oncolytic Vaccinia Virus Strains For The Immunotherapy Of Malignant Diseases
4
Objective of the study is to carry out a systematic analysis of the data available in current literature on the creation of the novel therapeutic vaccinia virus strains for the treatment of various malignant neoplasms, including ovarian and breast cancer.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles found in Pubmed on the subject published over the past 10 years.
Results. Virotherapy of cancer is a novel approach to the treatment of malignant diseases, based on the viruses, which possess natural oncolytic properties or are improved by genetic engineering. Oncolytic viruses infect and lyse cancer cells without harming normal cells, herewith many of them exhibit an ability of targeted stimulation of the immune system to fi ght tumor cells. Recombinant viruses, created on the basis of vaccinia virus, are opening great prospects in antitumor therapy due to the large size of their genome and high tumor selectivity. Expression in such vector of proteins that possess immunomodulatory and proapoptotic properties, contributes to increased effi ciency of the cross-activation of T-cells which recognize tumor cell antigens, including those involving dendritic cells.
Conclusion. Vaccinia virus is a powerful tool for multimodal cancer therapy. Over the past decade the area of recombinant virus research and development has been undergoing rapid growth, and dozens of new therapeutic strains are at various stages of clinical trials, that should undoubtedly contribute to improved survival of cancer patients.
Keywords: virotherapy of cancer, oncolytic viruses, vaccinia virus.
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BREAST CANCER
Talipov O.A., Ryabchikov D.A., Tchulkova S.V., Vorotnikov I.K., Kazakov A.M., Loginov V.I., Kazubskaya T.P., Vinokurov M.S., Osipova A.A., Berdova F.K.
Methylation Of Suppressor MicroRNA Genes In Breast Cancer
14
Objective of the study is to determine the profi le of methylation of suppressor miR -203а, -375, -124а-1/2/3, -137, -127, -125b-1, -130b, -107 genes in breast cancer.
Materials and Methods. The change in the methylation status of 10 genes in promoter CpG-islets: miR-203a, miR-375, miR-124a-1/2/3, miR-137, miR-130b, miR-107, miR-125b-1 and miR-127 was determined using the method of DNA bisulfi te conversion with subsequent methylation-specifi c polymerase chain reaction (PCR). The study was performed on a sample of 70 paired (tumor/unaffected breast tissue) DNA specimens obtained from breast cancer patients. The results were analyzed using standard statistical programmes STATISTICA, v. 10 and SPSS, v. 21.
Results. The frequency of miR 124а-1, -124а-3, -125b-1, -127, -137, -130b gene methylation in a tumor compared to histologically intact tissue was reliably higher (р<0,05). miR 124а-1 (75,7%, n=53 against 27,1%, n=19, р<0,05) and miR125b-1 (48,6%, n=34, р<0,05) gene methylation was observed most commonly. miR-125b-1, miR-127 hypermethylation in breast cancer was observed for the fi rst time. Reliable correlation between the methylation of several miR (-127, 137, 125b-1) genes with breast cancer progression indicators (stage, tumor size, metastasis into lymph nodes) was demonstrated. Co-methylation of separate miR was identifi ed (р<0,05).
Conclusion. The fi ndings on epigenetic disorders complement the «molecular profi le» of breast cancer and contribute to understanding its pathogenesis. The relationship between the methylation of a number of microRNA genes and breast cancer progression was found. The features of methylation of the genes, revealed under this study, will further enhance the development of the novel approaches to breast cancer diagnosis and prognosis.
Keywords: gene methylation, microRNA, breast cancer.
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OVARIAN CANCER
Dmitriev V.N., Dobrokhotova Yu.E., Mukhina T.S., Shevchyuk A.S., Syromyatnikova A.A., Koshurnikov А.Yu., Zhernakov Е.V
Malignant Ovarian Germ Cell Tumors. Literature Review
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Objective of the study is to carry out a systematic analysis of current literature related to the issues of diagnostics, staging, recurrence risk assessment, treatment strategy, follow-up, long-term outcomes of the treatment, general and recurrencefree survival of patients with malignant ovarian germ cell tumors.
Materials and Methods. The review comprises the data of foreign and Russian academic articles found in Pubmed on the subject published over the past 10 years.
Results. The paper provides the latest fi ndings on morphological and molecular diagnosis, the most effective treatment strategies at different stages of malignant ovarian germ cell tumors, the responses to therapy are evaluated, the issues of fertility preservation and hormone replacement therapy are addressed as well.
Conclusion. Unilateral adnexectomy with further BEP chemotherapy regimen is the standard of treatment of malignant ovarian germ cell tumors. In cases of immature highly-differentiated teratoma stage IA and dysgerminoma stage IA further adjuvant chemotherapy after an adequate surgical staging is not required. BEP chemotherapy regimen is a golden standard of the fi rst -line chemotherapy for malignant ovarian germ cell tumors.
Keywords: malignant germ cell tumors, treatment, fertility.
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СERVICAL CANCER
Bagrova S.G.
Immunotherapy Of Cervical Cancer. Are There Any Hopes For The New Opportunities?
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Objective of the study is to carry out a systematic analysis of the data available in current literature on the possibilities of immunotherapy of cervical cancer.
Materials and Methods. The review includes the data of foreign and Russian academic papers found in Pubmed on the subject published over the past 5 years.
Results. As of today immunotherapy is an important new part of the treatment of solid tumors, however, an interaction between immune preparations and chemotherapy, targeted therapy, surgical intervention and, most signifi cantly, radiation has not been yet clearly defi ned. Adding of inhibitors of immune response blockers to the existing chemotherapy regimens show encouraging results. Synergy of the combination of radiation therapy and immunotherapy in preclinical and clinical studies has been described, many clinical trials are being conducted to examine the safety and effi ciency of this approach.
Conclusion. Immunotherapy is an important novel therapeutic strategy for many patients with progressing cancer. Considering cervical cancer resistance to cytostatic agents, the possibilities of the treatment of this category of patients are very limited. As the occurrence of responses to immuno-oncology agents in gynecological population is rather modest, novel combinatorial approaches to their application together with radiation therapy are currently being investigated.
Keywords: immunotherapy, cervical cancer, checkpoint inhibitors, bevacizumab, chemotherapy, radiation therapy.
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INTERDISCIPLINARY QUESTIONS
Bergen T.A., Fokin V.A., Trufanov G.E., Smagina A.V., Soynov I.A.
Prognosis Of The Course And Outcome Of The Disease Based On The Findings Of Magnetic Resonance Imaging (MRI) In Gynecologic Oncology
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Objective of the study is to evaluate the significance of diffusion techniques of magnetic resonance imaging (MRI) in the prognosis of the course and outcome of the disease based on the assessment of the perifocal infiltration area in pelvic organ disorders in females.
Materials and Methods. Retrospective analysis of the examinations of pelvic organs of females performed on magnetic resonance scanner (MRI scanner) with the field induction of 1,5 Tesla was carried out. Totally 1730 patients with pelvic organ pathology had undergone examination, to harmonize the groups propensity score matching analysis technique was applied, after which a group of cancer pathology (n = 165) was identified, and a group of non-tumor pathology was identified as a comparison group (n = 165).
Results. Intergroup comparison of magnetic resonance imaging (MRI) parameters of patients with pelvic organ diseases, using linear regression analysis and ROC-curve plotting, was conducted. In the course of this study it was discovered that the probability of unfavourable outcome in such pelvic tumors as ovarian cancer, endometrial and cervical cancer is related to the values of apparent diffusion coeffi cient (ADC) from the area of perifocal changes. Thus, in ovarian cancer worsening of prognosis is associated with the registration of the value of apparent diffusion coeffi cient (ADC) from the area of perifocal infiltration being higher than 0,7×10–3 mm2/sec (sensitivity 93,7%, specifi city 52,1%); in endometrial cancer — higher than 0,3×10–3 mm2/sec (sensitivity 88,7%, specifi city 54,8%). If in cervical cancer the value of apparent diffusion coefficient (ADC) from the area of perifocal infiltration makes up more than 1,1×10–3 mm2/sec, the likelihood of worsening increases (sensitivity 80,3%, specifi city 52,2%).
Conclusion. The protocols of pelvic organ magnetic resonance imaging (MRI) examinations in gynecologic malignacies must include diffusion-weighted imaging with mandatory apparent diffusion coeffi cient (ADC) mapping. Values of apparent diffusion coeffi cient (ADC) should be assessed not only from the main focal lesion, but from the area of perifocal changes as well. The probability of a favourable outcome in gynecologic malignancy declines with an increase in the values of apparent diffusion coeffi cient (ADC) from the area of perifocal infi ltration.
Keywords: magnetic resonance imaging, MRI, apparent diffusion coefficient, ADC, oncology, ovarian cancer, endometrial cancer, cervical cancer, colon cancer.
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Payanidi Yu.G., Vinokurova S.V.
HPV-Associated Tumors Of Female Reproductive System. Risk Factors. Harm Reduction Conceptual Approach
51
Objective of the study is to conduct a systematic analysis of the data available in current literature on HPV-associated tumors of female reproductive system, on the main risk factors of their occurrence and to consider the ways of their prevention.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles found in Pubmed on the subject published over the past 5 years.
Results. Human papilloma viruses (HPV) can manifest as benign lesions on the skin and mucous membranes, as well as they can induce the occurrence of malignant tumors in humans. HPV plays a lead, but not a unique role in carcinogenesis of the majority of tumors. In addition to the virus, the presence of other factors (infl ammatory processes, heredity etc.) which modulate the progression of HPV-atypia up to invasive disease, is necessary. Smoking is considered to be one of such exogenous impacts as well. Tobacco smoke consists of more than 700 chemical substances, of which at least 69 cause cancer. Moreover, smoking aggravates the course and prognosis of a wide range of oncologic diseases.
Conclusion. Smoking is one of the risk factors of occurrence of the majority of HPV-associated tumors of female reproductive system. Promoting smoking cessation should become an essential contributor to the treatment of cancer in all oncologic programmes. In cases when patients can’t quit smoking completely within the shortest possible period of time, doctors should focus on harm reduction strategies, that is, to discuss with a patient the possibility of switching in a postoperative period to an alternative product, the one with a reduced or modifi ed risk, which should serve as an intermediate link on the pathway to smoking cessation, since it does not entirely reverse an adverse health effect.
Keywords: HPV-associated tumors, risk factors, heredity, smoking, harm reduction strategy
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Kreynina Yu.M., Shevchenko L.N., Kaskulova M.Kh., Dykina A.V., Smyslov A.V., Trotsenko S.D., Khoronenko N.A.
Novel Technologies Of Conformal Radiation Therapy In Advanced Present-Day Programmes Of Treatment Of Recurrent Cervical, Endometrial And Ovarian Cancer
60
Objective of the study is to outline development strategies of the use of the newest technologies of conformal radiation therapy in the treatment programmes recommended for the recurrence of female genital cancers of major localizations.
Materials and Methods. The study used the materials of clinical observations of patients with recurrence and metastasis of cervical, endometrial and ovarian cancers who had received conformal radiation therapy at Federal State Budgetary Institution «Russian Research Center of Radiography and Radiology of the Ministry of Healthcare of the Russian Federation» in 2012-2019.
Results. In accordance with the current Russian national and international clinical recommendations the article addresses methodological aspects of the choice and introduction of the most available conformal, photon-beam irradiation technologies in Russia’s practical radiation oncology for the treatment of different patterns of gynaecological cancer progression including the treatment of previously irradiated zones.
Conclusion. The use of high-precision radiation therapy techniques based on the up-to-date latest technologies of medical visualization in the treatment of recurrence and metastases of gynecologic cancer provides new opportunities to ensure control over the disease.
Keywords: cervical cancer, endometrial cancer, ovarian cancer, radiation therapy, conformal radiation.
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Shamarakova M.V., Asaturova A.V., Tregubova A.V.
Malignant Tumors In Pregnancy: Regression Mechanisms And Diagnostic Peculiarities
71
Objective of the study is to carry out a systematic analysis of the data available in current literature on the peculiar properties of tumors in pregnant women.
Materials and Methods. The review comprises the data of recent studies, with their results published in the key international academic journals over the past 5 years.
Results. Some of the data presented suggest that hormones and growth factors necessary for embryonic development, can affect tumor angiogenesis, epithelial-mesenchymal transition (EMT) and modulate immune tolerance. Progression of highgrade neoplasms with hCG, PlGF expression was demonstrated in a number of clinical observations, while inductive effect of gestation on low-grade tumors was not identified. A number of authors note that less favourable course and prognosis of malignant tumors in pregnancy are attributed to the peculiarities of their diagnosis and histological structure, rather than to the specific features of humoral regulation in pregnancy.
Conclusion. Apparently, peculiarities of growth and metastasis of the tumor in pregnancy derive from its topical identity, and to a considerable extent, from its histological type and immunophenotype.
Keywords: pregnancy, chorionic gonadotropin, placental growth factor, carcinoma.
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Usmanova E.B., Obukhova O.A., Shchelkova O.Yu.
Quality Of Life And Sexual Health Of Patients With Malignant Ovarian Neoplasms
77
Objective of the study is to make up a systematic review of current literature related to the issue of the quality of life and sexual health of patients with malignant ovarian neoplasms.
Materials and Methods. The review includes the data of current foreign academic literature of Pubmed base.
Results. The data of current foreign academic literature indicate a decline in the quality of life and the presence of a number of sexual health disorders in patients with malignant ovarian neoplasms.
Conclusion. The fi ndings stated above suggest the need to develop a programme of comprehensive psychosocial rehabilitation of patients with malignant ovarian neoplasms both in early and advanced stages of the disease.
Keywords: quality of life, sexual health, malignant ovarian neoplasms, psychosocial rehabilitation.
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