Vol 21, No 3 (2019)


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Effect of starting dose of regorafenib on overall survival of patients with metastatic colorectal cancer: a systematic review and meta-analysis

Fedyanin M.Y., Polyanskaya E.M., Tryakin A.A., Pokataev I.A., Tjulandin S.A.


Aim. To conduct a systematic review and meta-analysis of studies on the effect of starting dose of regorafenib on overall survival (OS) of patients with chemorefractory metastatic colorectal cancer. Materials and methods. We searched for research data in the PubMed. The analysis included all publications till 08.20.2019 which compared OS depending on the starting dose of regorafenib (160 mg or less) in the 1st course of therapy. Meta-analysis was conducted using Review Manager Ver. 5.3. Results. Two studies demonstrated decreased OS at starting dose of less than 160 mg (A. Adenis et al., 2016: risk ratio - RR 1.26, 95% confidence interval - CI 1.01-1.56; A. Aljubran et al., 2019: RR 2.25, 95% CI 0.93-5.43). Two studies showed an improvement in OS with a starting dose of less than 160 mg in the 1st course (T. Bekaii-Saab et al., 2018: RR 0.72, 95% CI 0.47-1,11; J. Gotfrit et al., 2017: RR 0.46, 95% CI 0.17-1.22). In two other studies, there was no effect of a starting dose of regorafenib on OS (K. Yamaguchi et al., 2019: RR 0.95, 95% CI 0.82-1.1; G. Argiles et al., 2019: RR 0,86, 95% CI 0.65-1.13). The meta-analysis did not reveal the effect of starting dose of the drug on OS: RR 0.97, 95% CI 0.78-1.21; p=0.79; I2=64. Conclusions. Reducing the starting dose of regorafenib in the 1st course does not decrease OS and can be recommended for routine clinical practice.
Journal of Modern Oncology. 2019;21(3):10-15
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Osimertinib for the first-line treatment of EGFR-positive non-small cell lung cancer

Reutova E.V., Laktionov K.P., Iudin D.I., Neliubina L.A., Gorokhova G.K., Egorova A.V.


In the past century, lung cancer has become one of the most prevalent malignant neoplasms. The prognosis for patients with metastatic and locally advanced non-small cell lung cancer (NSCLC) was extremely pessimistic. The overall survival on standard platinum-based chemotherapy did not exceed 10 months. The treatment tactics choice, namely choice of specific chemotherapeutic regimen, was empirical. The situation has changed dramatically with the study of molecular-genetic disorders that contribute to a tumor development and targeted therapy availability. Until recently, the main approach to the treatment of patients with NSCLC with activating mutations was the use of first-generation tyrosine kinase inhibitors (TKI), then, in the case of disease progression, the administration of next generations drugs or chemotherapy. However, this trend has been changing lately, new generation of targeted drugs have a significant advantage in time till progression, better intracranial control, a more favorable safety profile, that establish them as first-line treatment. Recent data confirms also an improvement of overall survival. This article discusses the situation in EGFR-postive NSCLC.
Journal of Modern Oncology. 2019;21(3):17-20
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Durvalumab in the treatment of locally advanced non-small cell lung cancer after chemoradiotherapy in a real practice

Sakaeva D.D., Ruchkin V.V., Goncharova O.V., Abbasova R.R., Mufazalov F.F.


In 2017 the first published PFS results of PACIFIC study demonstrated new opportunities of immunotherapy in locally-advanced unresectable non-small-cell lung cancer (NSCLC) after chemoradiation (CRT). The positive overall survival results in this trial were received next year. This trial has become the first positive study in the more then 10 years after failure of all trials which investigated different approaches for improvement efficacy of standard CRT (induction therapy, consolidation therapy, target therapy, increased RT dose). The PACIFIC trial has opened new opportunities to improve outcomes in this patient’s population. Durvalumab was registered in Russia in July 2019, however clinical experience of durvalumab administration is still limited and we need to build expertise in this field. In this article we present the first example of durvalumab therapy in post CRT period in Bashkortostan real clinical practices. Patient with IIIB st NSCLC started durvalumab therapy after standard CRT. The complete response was registered after 4 months of therapy and currently after 9 months of therapy it is still remain.
Journal of Modern Oncology. 2019;21(3):21-25
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Complex radiologic imaging of early breast cancer (literature review)

Aliyeva G.S., Korzhenkova G.P., Kolyadina I.V.


Clinicoroentgenological diagnosis of early breast cancer - BC (non-invasive or invasive small-sized cancers) is difficult due to the absence of any characteristic clinical symptoms and pathognomonic roentgenological signs of the malignant process. Screening of BC has shown to be one of the most successful projects for early diagnosis of malignancies, but the probability to receive false negative results using screening mammography reaches 12%, and, on the one hand, this is due to interval cancers, and on the other hand - to defects in the primary screening. Among the factors associated with the likelihood of ineffective screening of BC, the most authors highlight such as high breast density, preceding the breast biopsy for a benign process, young age, as well as the use of hormone replacement therapy. The main methods of instrumental BC diagnostics are mammography, ultrasound (US), magnetic resonance imaging (MRI) and positron emission tomography (PET). Mammography is the "gold standard" for both screening and best diagnostics, but is characterized by a high proportion of both false positive and false negative results, and this can be partially solved by the use of digital mammography with tomosynthesis (performing a series of mammography images obtained at different angles and producing the focused 3-D images). Contrast enhanced mammography allows to identify angiogenesis in the area of the predicted malignancy, but is characterized by a high radiation exposure. Breast ultrasound is characterized by low specificity of the method and the high dependence of the result of data interpretation depending on physician qualifications. MRI of the breast for screening is characterized by high sensitivity, but also high cost and high proportion of false positive results. The role of PET/computer tomography in the diagnosis of early BC remains unclear, and the informative value of research in patients with nonpalpable tumors is extremely low. The roentgenological picture of early BC is widely variable; characteristic features include the presence of clustered calcifications, lumps with jagged edges, rough multinodular lumps. However, in a significant proportion of women the only manifestation of early BC is the presence of microcalcinates. Careful analysis of the localization and the shape of microcalcinates and basic characteristics allows correctly interpret the roentgenological diagnosis and helps to choose the optimal diagnostic and treatment algorithm.
Journal of Modern Oncology. 2019;21(3):26-32
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Immunotherapy in combination with chemotherapy in triple-negative breast cancer - the first “target” therapy for the “target” patients’ population

Grechukhina K.S., Zhukova L.G.


The only option of systemic therapy for triple-negative breast cancer (TNBC) was cytotoxic chemotherapy until recently, moreover the unitary standard of care for metastatic forms was not strictly defined. That is why paradigm of the treatment remains at the discretion of the doctor and it is empirical, consisting of precise combination of drugs. TNBC is infamous as the worst prognostic subtype. The absence of estrogen and progesterone receptors expression and HER2 amplification in this subtype of tumors made the usage of target therapy impossible, which is essential for successful treatment of luminal and HER2 positive breast cancer subtypes. The data about potential immunogenicity of tumor in TNBC launched the investigation of immunotherapy efficacy in this subtype of breast cancer. International clinical trial Impassion130 has not only created the basis in this field of TNBC treatment but also identified and determined the “benefiters”-cohort of patients concerning one of the most important goals - improving overall survival, that is so significant for patients with this subtype of breast cancer.
Journal of Modern Oncology. 2019;21(3):33-37
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The predictive value of digital mammography, breast ultrasound and their combination in the diagnosis of early breast cancer

Alieva G.S., Korzhenkova G.T., Kolyadina I.V.


Aim. To assess the predictive value of digital mammography, breast ultrasound and a combination of these methods in the diagnosis of early breast cancer - BC (carcinomas in situ and invasive tumors up to 1.0 cm in size). Outcomes and methods. We retrospectively reviewed clinical records of 110 patients of the FSBI “N.N. Blokhin National Medical Research Center of Oncology» of the Ministry of Health of Russia Federation who were examined and treated for early BC (ductal carcinoma in situ, lobular carcinoma in situ, and invasive breast cancer no larger than 1.0 cm in size without regional or systemic tumor spreading). All patients were examined using digital mammography across two projections, with targeted magnification if it was necessary, as well as breast ultrasound with B-mode, Doppler ultrasound and elastography. We analyzed a frequency of establishing various BI-RADS categories according to data of mammography and breast ultrasound. We also assessed breast tissue density, a presence of nodules and calcifications and their radiological characteristics, as well as a frequency of false-negative results of mammography and breast ultrasound, their radiological characteristics, and causes of obtaining the false-negative results. According to the data of mammography and breast ultrasound, the study group was divided into 2 subgroups: patients who were diagnosed with BC (BI-RADS 5) and patients with changes in the breast which were not clearly interpreted as malignant (BI-RADS 0-4). Statistical analysis was carried out using the SPSS 20.0 program; differences were considered statistically significant with p<0,05. Results. According to the data of mammography, BI-RADS category 5 and 4 were determined in 80 (75,5%) and 9 (8.5%) patients, respectively; in other cases, the findings were interpreted as BI-RADS category 0-3. BC diagnosis (BI-RADS 5) was established significantly more often compared to BI-RADS 4 at a low breast tissue density (82.6% vs 50%, p=0.004), the presence of breast nodules (70% vs 7.7%, p<0.0001) and calcifications (68.8% vs 30.7%, p=0.002) and malignant changes in the microcalcifications (52.7% vs 25%, p=0.002). According to the data of breast ultrasound, BI-RADS category 5 and 0-4 were determined in 78 (73.6%) and 28 (26.4%) patients, respectively. The most pathognomonic ultrasound signs of early BC in the study group included: the presence of irregular hypoechoic masses with uneven not circumscribed margin, of non-parallel orientation, with an echogenic halo, acoustic shadowing and diffuse vascular changes. In 8 out of 26 patients whose BI-RADS category, based on mammography data only, was interpreted as 0-4, additional breast ultrasound increased the BI-RADS category to 5. The findings that allowed to establish a correct radiological diagnosis were: irregular shape of masses, uneven not circumscribed margin, hypoechoic structure, non-parallel orientation, presence of an echogenic halo and acoustic shadowing. Conclusions. The combination of mammography and breast ultrasound increased the likelihood of the identification of malignant breast neoplasms and increased the frequency of interpretation of the revealed findings as BI-RADS category 5 from 75,5 to 83%. Along with this, the frequency of determining BI-RADS category 4-5 increased from 85.6 to 93.5%. The rationale of using this combination of diagnostic methods for screening BC in Russia can be assessed by conducting a larger study and after an analysis of its economic efficiency.
Journal of Modern Oncology. 2019;21(3):38-45
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The efficacy of neoadjuvant chemotherapy and survival in older patients with stages II to III triple-negative breast cancer

Gordeeva O.O., Kolyadina I.V., Zhukova L.G., Gan'shina I.P., Komov D.V., Meshcheriakov A.A.


Background. Breast cancer (BC) maintains the leading position in the structure of the morbidity and mortality from malignancies. Triple-negative BC (TNBC) is the most aggressive subtype among all types of BC. The adequate and timely initiation of neoadjuvant chemotherapy (NAC) determines the further prognosis of the disease in case of early and locally advanced TNBC. Patients over 60 years old are the special subgroup, but it has not been previously considered separately. Aim. To determine the efficacy of NAC and survival in elderly patients with stages II to III TNBC. Materials and methods. Since 2014, 92 patients with histologically verified early and locally advanced TNBC have received NAC, followed by surgery ± adjuvant therapy. NAC was conducted under the following scheme: cisplatin 75 mg/m2 on day 1, paclitaxel 80 mg/m2 on days 1, 8 and 15 of 28-day cycle, for six cycles. After the end of NAC, patients underwent surgery and a follow-up assessment of the degree of therapeutic pathomorphism in the primary tumor and regional lymph nodes. Further on, the correlation analysis was carried out between clinical characteristics and the degree of therapeutic pathomorphism. Results. We analyzed the data from the 92 patients, 22 (23.9%) patients of them were in older age group. At the time of disease diagnosis, the patients older than 60 years of age had a greater involvement of regional lymph nodes (N3: 40.9% vs. 20.0%, p<0.05). Women older than 60 years of age received statistically and significantly less volume of the planned NAC (65.7% vs. 22.7%, p<0.05). This could be due to the significantly more frequent toxicity: nephropathy (54.5% vs 17.1%, p<0.05) and polyneuropathy (22.7% vs. 17.1%, p=0.054). We noted the lower frequency of the achieving complete clinical (28.6% vs. 41.4%, p=0.654) and pathomorphological response (51.6% vs 71.7%, p<0.05), that could be associated with both late diagnosis of the disease and incomplete volume of planned NAC. The local progression (45.5% vs. 22.9%, p<0.05), as well as the visceral metastases (36.4% vs. 17.1%, p<0.05) were more common identified characteristics in women older than 60 years of age. Women older than 60 years of age had worse survival rate (both, relapse-free and overall survival, p<0.05). We also received data concerning different localizations of metastasis in patients of different age groups: the predominant lesion of the central nervous system (50%) in patients younger than 60 years of age and liver damage (40%) in patients 60 years of age and older. Conclusions. The results of our analysis show significant differences in the efficacy, tolerability and long-term results of the treatment of older patients and require the conversion of the views on the course of the disease in patients over 60 years of age.
Journal of Modern Oncology. 2019;21(3):46-51
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Neuroendocrine carcinoma of the prostate (review of the literature)

Abbasova D.V., Polikarpova S.B., Kozlov N.A., Baranova M.P., Kovalenko I.P., Ignatova E.I.


Neuroendocrine neoplasia (NEC) of the prostate gland is a rather rare extrapulmonary neuroendocrine carcinoma and makes up only 0.5 to 1% of all malignant neoplasms of this localization. NEC of the prostate gland is a tumor of epithelial origin, histologically and immunohistochemically identical to analogues in the lungs and digestive system. When stained with hemotoxylin-eosin, neuroendocrine cells cannot always be visualized; they are best recognized by the immunohistochemical method of investigation using specific markers. Currently, a number of neuroendocrine markers are used, the expression of which may indicate a neuroendocrine nature. Androgen neuroendocrine cells themselves are independent and do not cause an increase in the concentration of prostate-specific antigen. Prostate NECs are represented by some histological forms according to WHO classification (2015): 1. Adenocarcinoma with focal neuroendocrine differentiation. 2. Well-differentiated neuroendocrine tumor. 3. Small cell neuroendocrine cancer is a high - grade tumor with high malignant potential. 4. Large cell neuroendocrine cancer is a high - grade tumor. Due to the rarity of NEC of the prostate, a specific algorithm for diagnosis and treatment has not been developed, as a rule, they are similar to methods of other malignant forms of prostate cancer and neuroendocrine tumors.
Journal of Modern Oncology. 2019;21(3):52-55
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Modern ultrasound technologies in monitoring the effectiveness of chemotherapy for cervical cancer

Musaeva Z.R., Chekalova M.A., Mesheryakov A.A.


Cervical cancer remains one of the most important social and medical problems worldwide due to the increase in morbidity and mortality. Improvement of existing and development of new options for diagnosis and treatment of common stages of cervical cancer is an urgent problem of modern Oncology. In accordance with the standards of treatment for advanced cervical cancer, drug, radiation therapy and surgical treatment in various modifications are used. Neoadjuvant chemotherapy can reduce the volume of tumors, which helps to achieve optimal resectability of the tumors, increases the ablasticity of the operation. In addition, it improves survival. An accurate assessment of the effectiveness of treatment is one of the important factors in the overall treatment. Complex ultrasound diagnostics is the most affordable and common imaging method, possessing a number of important technologies, allowing you to get the most objectively visualized tumors, uterus, prevalence, blood flow features and to receive timely information about tumor regression. In connection with the introduction of new technologies, a significant expansion of the capabilities of ultrasound diagnostics in oncology as a whole is observed today. The most promising of them are ultrasound elastography and contrast-enhanced ultrasound. The review is devoted to the possibilities of these methods in assessing the effectiveness of neoadjuvant chemotherapy.
Journal of Modern Oncology. 2019;21(3):56-61
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