Vol 16, No 4 (2014)


Press release

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Perjeta™ (pertuzumab) in combination with Herceptin® (trastuzumab) and docetaxel increases in life expectancy of patients with HER2-positive metastatic breast cancer (mBC) by 15,7 months compared with standard regimen Herceptin/docetaxel. The data from the phase III CLEOPATRA study.
Journal of Modern Oncology. 2014;16(4):5-6
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Press releaseThe resolution of the expert council for targeted therapy of radioactive iodine-refractory differentiated thyroid cancer

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В Москве 21 апреля 2014 г. состоялось первое заседание Экспертного совета по вопросам таргетной терапии дифференцированного рака щитовидной железы (ДРЩЖ), резистентного к терапии радиоактивным йодом. Рабочая группа экспертов с позиции доказательной медицины разработала критерии резистентности ДРЩЖ к терапии радиоактивным йодом, которые были озвучены и приняты 16 сентября 2014 г. в г. Казани в рамках VIII Съезда онкологов и радиологов стран СНГ и Евразии.
Journal of Modern Oncology. 2014;16(4):8-10
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Modern possibilities of HER2 positive breast cancer treatment (based on clinical trials)

Kolyadina I.V., Poddubnaya I.V.


This review includes the main steps of anti-HER2-therapy for breast cancer (BC). Up to 30% of breast tumors overexpress epidermal growth factor receptor HER2/neu, and this expression is correlated with poor prognosis and course of the disease. Determination of HER2-status in BC is mandatory for all stages, it is necessary to evaluate the prognosis and development of optimal therapeutic algorithm. The first targeted therapy developed in 1992 for the treatment of HER2-positive BC, has become trastuzumab (Herceptin). The unique mechanism of Herceptin (targeted blockade of HER-dependent signaling pathway, the blockade of the activation of PI3K and MAPK signaling pathway, activation of antibody-dependent cellular cytotoxicity, etc.) and high efficiency have significantly changed the prognosis of HER2-positive BC. The important role of 1-year adjuvant therapy with Herceptin has showed in large international trials (HERA, NSABP B-31, NCCTG 9831, BCIRG 006) for reducing the risk of recurrence (50%) and death (30%) in HER2-positive BC. Neoadjuvant chemotherapy with trastuzumab has studied in the large randomized trials (NOAH, GeparQuattro, GeparQuinto), which has been shown to benefit of Herceptin in the rate of pathological complete response and significant improvement of survival. The effectiveness of Herceptin in metastatic HER2-positive BC has showed in the large studies (M7701, HO648g, BCIRG 007, HERNATA, etc.) The advent of pertuzumab opened new perspectives for the treatment BC: pertuzumab inhibits HER2-receptor dimerization with other HER- receptors (HER1-3) and blocks the HER-mediated signaling pathways, activates of antibody-dependent cellular cytotoxicity. The combination of pertuzumab and trastuzumab blockade provides more HER2-mediated intracellular signaling pathways than either drug alone, which leads to a more pronounced anticancer response. In a large randomized study CLEOPATRA had shown unprecedented results of treatment of metastatic or recurrent BC: the increasing median of overall survival up to 56,5 months, regardless of age, race, the prior treatment, hormone receptor status and location of metastases. The benefit of pertuzumab has shown in old patients, patients with brain metastases, as well as a significant increase in progression-free survival. The new class of anti-HER2-agent - conjugates, appeared last time. Trastuzumab emtanzin (T-DM1) - the first conjugate the targeted monoclonal antibody trastuzumab, cytotoxic chemotherapy agent (DM1) and linker. Antitumor effect of T-DM1 sum of the effects of trastuzumab (targeted blockade of HER-dependent signaling pathway) and targeted delivery of high effective agent (DM1), which causes cell death by disrupting microtubule polymerization and cell cycle arrest. Efficiency T-DM1 has shown to increase disease-free survival, rate and duration of response and overall survival in patients with HER2-positive advanced BC pretreated with taxanes and Herceptin (EMILIA trial). Modern treatment options in HER2-positive BC perfectly combine high efficiency, safety and saved the quality of life.
Journal of Modern Oncology. 2014;16(4):10-20
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The effect of combinated treatment of a metastatic HER2-positive stomach cancer

Khvastunov R.A., Nenarokomov A.Y., Tolstopiatov S.E., Babina K.G.


Trastuzumab in combination with standard chemotherapy has shown its effectiveness in treating HER2-positive metastatic gastric cancer. The median overall survival in its application is 16,8 months compared with 11,8 months when chemotherapy using alone. Authors demonstrate the case of the successful using trastuzumab in the third line chemotherapy in patients with primary unresectable metastatic gastric cancer. As a result of the 12 courses of therapy almost complete tumor regression was achieved. It allowed to perform R0- gastrectomy. Currently, the patient continues trastuzumab treating in monoregime.
Journal of Modern Oncology. 2014;16(4):21-23
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Tumor biology or adjuvant systemic therapy: what determines the risk of recurrence in breast cancer stage I?

Kolyadina I.V., Poddubnaya I.V., Trofimova O.P., Frank G.A., Karseladze A.I., Komov D.V.


Aim: to study the prognostic value of clinical and morphological factors for the risk of recurrences in breast cancer stage I.Materials and methods: In study included 1341 women with breast cancer stage I (T1a-b-cN0M0), treated in the RCRC and RMAPE 1985-2012. We analyzed the clinical factors (age, volume of surgery, radiotherapy, type of adjuvant systemic therapy) and morphological factors (status of estrogen and progesterone receptors, HER2-status, proliferation activity index Ki-67, biological subtype, presence of lymph vascular invasion and intraductal component and the tumor size T1a-b-c). We assessed the risk of recurrence (median follow up - 96 months), the rate of relapse and disease-free survival in different subgroups using univariate and multivariate COX-regression analysis. Results: In univariate COX-regression analysis we found the prognostic value for the risk of recurrences of such morphological factors: grade of tumor ( p =0,034), histological type ( p =0,025), tumor size T1a-b-c ( p =0,004), presence of lymph vascular invasion ( p =0,03) and biological subtype of breast cancer ( p =0,002). The most favorable is the luminal A subtype with minimal rate of distant relapses (1,6%), the maximum time to progression (median - 48 months) and the best rate of the 5- and 10-year disease-free survival (97,2 and 93,8% respectively). The most important clinical factors were age ( p =0,001), the volume of surgery ( p =0,032), the using of «boost» after breast conservingtherapy ( p =0,007), and presence of adjuvant systemic therapy (chemotherapy, endocrine therapy or both therapy in accordance with the biological subtype, p <0,0001). In multivariate regression analysis, only two factors were significant for predicting the risk of recurrence of breast cancer stage I ( p <0,05): biological subtype and adjuvant systemic treatment. Compared with luminal A subtype the risk of relapse is significant higher in luminal B subtypes (HER2-negative: HR 1,393; HER2-positive: HR 1,321), in triple negative subtype - HR 2,297 and, especially, in hormone negative HER2-positive breast cancer - HR 6,001, p =0,04. Adjuvant systemic therapy reduce the risk of recurrence until 74% in breast cancer stage I (HR 0,276; p <0,0001).Conclusion: The tumor biology and adjuvant systemic therapy determines prognosis in breast cancer stage I.
Journal of Modern Oncology. 2014;16(4):24-30
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Male breast cancer: review of the literature

Nikolaev K.S., Semiglazov V.F., Semiglazov V.V.


Male breast cancer (MBC) is a rare condition that accounts for 0,1% of all male cancers. Our current evidence base for treatment is derived from female breast cancer (FBC) patients. Risk factors for MBC include age, genetic predisposition, race, sex hormone exposure, and environmental factors. Most patients present later and with more advanced disease than comparable FBC patients. Tumors are likely to be estrogen receptor and progesterone receptor positive, with the most common histologic type being invasive ductal carcinoma. Triple assessment remains the criterion standard for diagnosis. Primary MBC is mostly managed initially by simple mastectomy, with the option of breast conserving surgery, which carries an increased risk of recurrence. Sentinel node biopsy is recommended as the initial procedure for staging the axilla. Reconstructive surgery focuses on achieving primary skin closure, and radiotherapy largely follows treatment protocols validated in FBC. We recommend chemotherapy for men with more advanced disease, in particular, those with estrogen receptor negative histology. MBC responds well to endocrine therapy, although it is associated with significant adverse effects. Third-generation aromatase inhibitors are promising but raise concerns due to their failure to prevent estrogen synthesis in the testes. Fulvestrant remains unproven as a therapy, and data on trastuzumab is equivocal with HER2-receptor expression and functionality unclear in MBC. In metastatic disease, drug-based hormonal manipulation remains a first-line therapy, followed by systemic chemotherapy for hormone-refractory disease. Prognosis for MBC has improved over the past 30 years, with survival affected by disease staging, histologic classification, and comorbidity.
Journal of Modern Oncology. 2014;16(4):31-37
pages 31-37 views

Surgical results in patients 75 years and older with gastric cancer

Rokhoev G.A., Stilidi I.S., Nered S.N.


With the increase in life expectancy, the proportion of elderly patients with gastric cancer is constantly increasing.Objective: To research the clinical and morphological features and possibilities of surgical treatment of gastric cancer in patients 75 years and older.Materials and methods: A retrospective analysis of 839 patients with GC underwent to surgical treatment in the thoraco-abdominal department Russian cancer research center N.N.Blokhin during 1990-2010 years. 286 elderly patients (>75 years), including 62 patients over 80 years. Patients <75 years (n=553) in the control group.Results: The study of clinical and morphological characteristics of GC revealed a number of features in patients >75 years compared with patients in the control group: the more frequent lesion of the distal part of stomach, the prevalence of exophytic tumor growth and the nature of low-grade histological types, the high frequency of multiple primary tumors. The rate of surgical complications and mortality in the elderly group 40,2 and 5,2%, higher than in patients >75 years old 30,9 and 2,9%. Basically, increasing the number of the surgical complications and the mortality observed after palliative surgery. Overall 5-year survival as a reference to the stage, and in the analysis depending on the type and surgical volume was significantly worse in patients >75 years old. However, specific survival analysis revealed no statistically significant differences between groups. Expansion of surgical volume in elderly patients to total gastrectomy for cancer of the stomach antrum with the transition to the body did not improve the 5-year survival. Overall survival rate after D1-1,5- and D2-lymph node dissection in patients older than 75 years old do not have significant differences.Conclusion: Gastric cancer in elderly patients does not have aggressive course and the deterioration in overall survival in old age group is mainly due to mortality from comorbidities. Improvement in overall survival in patients >75 years old extended surgical treatment have been identified.
Journal of Modern Oncology. 2014;16(4):37-44
pages 37-44 views

Features of development of metachronous and synchronous tumors in the population of Belgorod region associated with the consequences of the Chernobyl accident

Kovalenko B.S., Golivets T.P., Podvyaznikov S.O.


The analysis of the prevalence of primary multiple malignant neoplasms (PMMN) in the Belgorod region (BR), one of the 14 regions ofRussia, officially referred to the victims of the Chernobyl radiation accident in 1986. The incidence of metachronous and synchronoustumors in the composition of PMMN was analyzed in the dynamics of the five-year observation periods. It is established that during the first four observation periods (1981-1985, 1986-1990, 1991-1995, 1996-2000) were recorded mainly PMMN with metachronous development. Moreover, before the emergency period (1981-1985) and in the first ten years after the accident (1986-1995) the emergence of second tumors was observed mainly after 10 or more years after treatment of the first tumor. In subsequent periods, including 1996-2010, the timing of detection of the second and subsequent metachronous tumors after treatment of the first tumor was reduced on average by 5-10 years. In 2001-2010 the vast majority of newly diagnosed preneoplasia had synchronous character development. It can be assumed that the peculiarities of the formation PMMN in the population BR, with the predominant development of synchronous tumors in 2001-2010 (15 years after the accident), can be caused by the reduction in biological latent period metachronous tumors, as a result of the remote effects of low doses of radiation due to the Chernobyl accident.
Journal of Modern Oncology. 2014;16(4):44-49
pages 44-49 views

Keratoacanthoma: possible management approaches. Case reports

Teterin K.A., Kizhaev Y.E., Bolotova N.P.


We report a 91-year-old male patient with keratoacanthoma (KA) of left temporal skin with atypia, treated with laser vaporization followed by radiation therapy. Also we report a 77-year-old female patient with KA of right temporal skin without atypia, treated with laser vaporization alone. The KA and squamous cell carcinoma similarity demands oncologist assistance for KA management.
Journal of Modern Oncology. 2014;16(4):49-52
pages 49-52 views

Radiation treatment of the primary vulvar Pagetʼs disease: case report

Razumova E.L., Kizhaev Y.E., Ukolova E.A.


We report a 69-year-old female patient with primary non-invasive isolated extra-mammary Pagetʼs disease of the vulva. EBRT resultedin full resorption of the lesion without auxiliary techniques, making EBRT to be considered as an alternative to surgery in some cases.
Journal of Modern Oncology. 2014;16(4):53-56
pages 53-56 views

Clinical case long-term care of the patient with mCRPC

Zaborskiy I.N., Karjakin O.B.


Patients with metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis, and those patients with metastases areexpected to survive ≤19 mo. As patientsʼ disease progresses, quality of life deteriorates, and until recently, few treatment options were available. Several new therapies have shown an improvement in overall survival for patients with mCRPC who have already received chemotherapy with docetaxel. The impact of these new data on daily clinical practice, treatment sequencing, and best care for individual patients is not yet fully understood. Early detection of castration resistance before the development of clinical symptoms and significant prevalence of tumor gives patients the opportunity to receive as many lines of drug therapy with a satisfactory quality of life, which, of course, leads to an increase in overall survival. Here we present clinical case long-term care of the patient with mCRPC.
Journal of Modern Oncology. 2014;16(4):58-60
pages 58-60 views

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