Vol 23, No 4 (2021)


Gastric cancer: Russian clinical guidelines

Besova N.S., Kalinin A.E., Nered S.N., Triakin A.A., Gamaiunov S.V., Kozlov N.A., Stilidi I.S., Karachun A.M., Kononets P.V., Malikhova O.A., Riabov A.B., Khomiakov V.M., Fedenko A.A., Bolotina L.V., Falaleeva N.A., Nevol'skikh A.A., Ivanov S.A., Khailova Z.V., Gevorkian T.G., Butenko A.V., Gil'mutdinova I.R., Eremushkin M.A., Ivanova G.E., Kondrat'eva K.O., Konchugova T.V., Krutov A.A., Obukhova O.A., Semiglazova T.I., Filonenko E.V., Khulamkhanova M.M., Romanov A.I.


Gastric cancer remains one of the most common malignancies in Russia. Despite steady decrease of gastric cancer incidence it still reaches 24.65 per 100 000 population (crude rate) in 2019 with about 36 000 new cases annually. More than 29 000 people die of gastric cancer every year. High mortality rate is mostly caused by an extremely significant proportion of patients with metastatic disease which reached 40.1% in 2019. The majority of cases is related to Helicobacter pylori infection, salty diet, tobacco exposure as well as hereditary syndromes. Staging of locally advanced gastric cancer includes contrast-enhanced computed tomography of the thorax, abdomen and pelvis as well as diagnostic laparoscopy with peritoneal washings. In patients with inoperable or disseminated cancer of the stomach additional analysis for HER2, microsatellite instability and PD-L1 status is recommended. Endoscopic or laparoscopic resection remains the mainstay of treatment in patients with early cancer. Laparoscopic gastrectomy in patients with locally advanced cancer is reserved for high-volume centers with extensive experience with the procedure. Recently, perioperative cytotoxic therapy became the standard of treatment in patients with locally advanced gastric cancer. FLOT regimen is recommended while FOLFOX6 or XELOX are considered possible in the elderly or frail patients. Drug therapy includes standard doublet or triplet chemotherapy regimens for metastatic disease with trastuzumab for HER2(+++) patients. Patients with MSI-H tumors can be treated with pembrolizumab starting with 2nd line while nivolumab is reserved for the 3rd and further lines regardless of PD-L1 status. Importantly, this year guidelines include multimodal prehabilitation including physical exercise, nutritional support and psychological counselling as a possibility in all patients in need of surgery. Also standardized enhanced recovery protocols are recommended for usage during the perioperative period.

Journal of Modern Oncology. 2021;23(4):541-571
pages 541-571 views

The consensus on the prevention and correction of rash in patients with HR+ HER2- metastatic breast cancer treated with alpelisib

Shlivko I.L., Garanina O.E., Artamonova E.V., Ganshina I.P., Zhukova L.G., Koroleva I.A., Michenko A.V., Semiglazova T.Y., Filonenko D.A.


The consensus on the prevention and correction of rash in patients with HR+ HER2- metastatic breast cancer treated with alpelisib was developed by the experts of the Russian Society of Clinical Oncology and dermatovenerologists. PIK3CA mutation is a poor prognostic factor for HR+ HER2- metastatic breast cancer. Alpelisib demonstrates efficacy in patients with PIK3CA mutation, but treatment might be associated with adverse events that include rash. All-grade rash was reported in 35.6% patients in SOLAR-1 trial (n=284). According to the published real-world data, for Russian population (n=19) all-grade rash was reported for 37% patients. The consensus contains practical recommendation on management of patients with rash of different grade.

Journal of Modern Oncology. 2021;23(4):572-576
pages 572-576 views

The era of immuno-oncology in onco-urology: what have we achieved? The review of the symposium of the alliance between Merck and Pfizer held within the framework of the XXV Russian Oncology Congress. November 9, 2021


On November 9, 2021 in the framework of the XXV Russian Oncology Congress the symposium was held where the various issues of approaches of drug treatment and surgical treatment of metastatic renal cell carcinoma and urothelial cancer were discussed. New drugs are being appeared, large clinical studies are being conducted, new prospects for immunotherapy of malignant neoplasms are being developed, nowadays. One of the new options is immune checkpoint inhibitors. In the framework of the symposium were presented the results of two trials – the JAVELIN Renal 101 and the JAVELIN Bladder 100, showing the efficacy and safety of the PD-L1 inhibitor avelumab. The symposium was supported by the alliance between Merck and Pfizer.

Journal of Modern Oncology. 2021;23(4):578-587
pages 578-587 views

Innovations in practice. 5 years of palbociclib experience in the Russian Federation. Overview of web-conference took place on 8 October 2021


The educational cycle "Venus of The Future: the discoveries and new traditions in the treatment of mBC" was initiated by Pfizer with the support of TS Oncology. During several web-conferences planned in 2021–2022 key experts discussed implementation in clinical practice and availability of innovative approaches for treatment patients with HER-negative mBC in the Russian Federation. The first web-conference of the cycle - "Innovations in practice. 5 years of palbociclib experience in the Russian Federation" took place on October 8, 2021 and was dedicated to the 5th anniversary since registration in the Russian Federation of palbociclib – 1st CDK4/6 inhibitor (CDK4/6i) in our country. Key Russian experts in oncology, who were at the forefront of introducing CDK4/6i into routine clinical practice, took part in the event and outlined the importance of considering the differences among iCDK 4/6 in terms of the tolerance profile and monitoring requirements, as well as taking into account practical experience when making desicion to choose specific product. Experts agreed that palbociclib have a great advantage over other products in the class due to significant amount of RCT and RWE data, as well as broad practical experience (more than 5 years) in the Russian Federation and in the world.

Journal of Modern Oncology. 2021;23(4):588-592
pages 588-592 views

Malignant neoplasms in HIV patients in Russia: the story over a 20-year period

Nekrasova A.V., Rassokhin V.V., Falaleeva N.A., Grivtsova L.Y., Gusev D.A.


According to the official statistics, by the beginning of 2021, the overall number of registered HIV cases in Russia exceeded 1.1 million. For about 100 000 new HIV-infected patients have been registered annually in Russia recent years. Russia occupies one of the leading places in the incidence of HIV infection, and the growth rate of new HIV cases is not decreasing. HIV-infected patients have higher incidence of malignant neoplasms (MN) in comparison with the overall population and have the highest cancer mortality rates. The problem of HIV-associated malignancies is at the junction of two socially significant issues, and this situation especially taking into account in Russian Federation. The problems of diagnosis and treatment of MN are becoming topical, and it is extremely important to study HIV-associated malignancies epidemiology in the Russian Federation. This will help to create effective algorithms for organizing dispensary observation for HIV infected people, will help to early diagnosis of the disease, timely initiation of treatment and, as a result, will help to achieve the best oncological results.

Journal of Modern Oncology. 2021;23(4):593-597
pages 593-597 views

Disseminated Kaposi sarcoma with osseous metastases in patients with HIV infection. Case report

Ognerubov N.A., Antipova T.S.


Background. Kaposi sarcoma is a low-grade vascular tumor affecting blood and lymphatic vessels associated with the human herpes virus type 8 (HHV-8). As a rule, the skin of the lower extremities is involved in the process first of all, and then other organs and lymph nodes are involved. There are 4 various types of the disease with different clinical picture: the classic, the endemic, the epidemic and immunosuppression subtype. The epidemic subtype is the most common and has the most aggressive course, with specific lesions of a multiple kind, including the skin, mucous membrane layers, the lymph nodes, the gastrointestinal tract, the lungs and the spleen. Osseous metastases are extremely rare.

Aim. Show the case of Kaposi sarcoma with osseous metastases in patient with the human immunodeficiency virus (HIV) infection.

Results. We observed a 43-year-old patient with HIV infection and stage 4b Kaposi sarcoma against the background of the irregular antiretroviral therapy in the progression stages. The duration of the anamnesis was 32 months. The clinical debut of the cancer process was noted with skin lesions on the shoulder. Histological and immunohistochemical analysis of skin biopsies showed the morphological picture of Kaposi sarcoma. HHV-8 was expressed in tumor cells. During the endoscopic examination the lesions of oral mucosa, stomach and proximal colon were confirmed morphologically, and spiral computed tomography of the chest revealed the lesions in the lungs. On this point, the patients received oxaliplatin-based chemotherapy and aetoposidum for 6 months and against the background of this treatment we observed the disease progression associated with the involvement of the retroperitoneal lymph nodes, the left adrenal gland and the penis. Circumcision was performed in the case associated with the involvement of the penis. The treatment was continued. The lytic left iliac bone lesion, the retroperitoneal lymph nodes, the iliac lymph node groups, as well as the left inguinal lymph nodes, the left adrenal gland and the lungs were characterized by a high F-18 FDG uptake after 3 months of the treatment, according to the results of Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography combined with computed tomography (PET/CT).

Conclusion. Kaposi sarcoma in patients with HIV infection had an aggressively course with disseminated skin lesions and internal organ involvement, including bones as showed in this clinical case. In this case, the axial skeleton was more commonly involved. PET/CT is a diagnostic imaging method in the differential diagnosis and determination of the prevalence of the cancer process.

Journal of Modern Oncology. 2021;23(4):598-602
pages 598-602 views

Features of response to modern neoadjuvant chemotherapy with dual anti-HER2 blockade (trastuzumab and pertuzumab) in the patients with HER2-positive breast cancer stage II–III

Morozov D.A., Kolyadina I.V., Poddubnaya I.V., Ganshina I.P., Khokhlova S.V., Kоmetova V.V., Rodionov V.V.


Background. Neoadjuvant chemotherapy (NACT) with dual anti-HER2 blockade has become a priority in the treatment of patients with HER2+ breast cancer (BC) stages II–III. However, the question of the accordance of various systems for assessing tumor response to NACT, as well as identifying predictor factors for achieving a complete pathomorphological response (pCR) in HER2+ BC remains open.

Aim. To assess the accordance of various systems for assessing tumor response to neoadjuvant chemotherapy (NACT) in patients with HER2+ BC and to identify predictor factors for achieving pCR and residual cancer burden.

Materials and methods. The study included 49 women with HER2+ BC stage II–III, who underwent NACT with anti-HER2 blockade, followed by surgical treatment and morphological analysis of the results. The median age of the patients was 47 years; 91.8% had tumor size ≥T2, N+ status – 71.4%; tumor grade G3 – 73.5%, luminal and non-luminal HER2+ subtype – 44.9 and 55.1% of patients, respectively. Ki67≥30% was observed in 93.9% of cases, the level of TILs in the tumor was <10%, 10–20% and >20% – in 38.1, 9.5 and 52.4% of cases, respectively. The patients received combinations of anthracyclines and taxanes or the anthracycline-free regimen of docetaxel + carboplatin; 87.8% of patients received a dual blockade of trastuzumab + pertuzumab, and 12.2% – trastuzumab. After the end of NACT, all patients underwent a radical surgery (mastectomy or breast-conserving) with an assessment of the pathomorphological response, the pathomorphological stage of ypTN, and the residual cancer burden according to the RCB system.

Results. The rate of complete pathomorphological response (tpCR/RCB-0/ypT0N0) in HER2+ BC was 61.2%; significant predictors of achieving tpCR were only 3 factors: primary operable BC stages (T1–3N0–1) – the rate of tpCR was 71.4%, the level of TILs>20% – the proportion of tpCR reached 95.5%, and the dual anti-HER2 therapy (trastuzumab + pertuzumab) – tpCR was 65.1%. Residual tumor was presented by classes RCB-I, RCB-II, RCB-III in 10.2, 24.5, 4.1%. The RCB-I class included of patients with a residual tumor less than 1.0 cm in the absence of regional lymph node involvement (80% of cases); class RCB-II was represented by the presence of a residual tumor less than 2.0 cm in combination with the absence or presence of residual metastases in 1–3 lymph nodes (83.4%), and class RCB-III was presented the residual tumors ≥2.0 cm and N1–2 status in 100% of cases (p<0.0001).

Conclusion. Modern NACT with dual anti-HER2 blockade (trastuzumab + pertuzumab) are highly effective – the rate of tpCR is 61.2%, and in the presence of high TILs>20% reaches 95.5%. Residual tumor in most cases was presented by class RCB-I or RCB-II, only 4% of patients had massive residual tumor load (class RCB-III).

Journal of Modern Oncology. 2021;23(4):603-609
pages 603-609 views

The therapy for early relapsed chronic lymphocytic leukemia: the development of the problem The results of the project with the discussion concerning the possibility of optimization approaches for the therapy


The Russian Oncohematology Society with the support of AbbVie completed the project that allows Russian hematologists to discuss the possibilities of optimization approaches for the therapy for early relapsed chronic lymphocytic leukemia, during 2021. The consolidated opinion of the specialists for several clinical situations was formulated at the final meeting.

Journal of Modern Oncology. 2021;23(4):610-611
pages 610-611 views

Pharmacoeconomic analysis of acalabrutinib in patients with chronic lymphocytic leukemia

Nedogoda S.V., Salasyuk A.S., Barykina I.N., Lutova V.O., Popova E.A.


Aim. Pharmacoeconomic analysis of new Bruton tyrosine kinase inhibitor for the treatment of high-risk adult patients with chronic lymphocytic leukemia (CLL) within the framework of health state budget.

Materials and methods. In the course of this study, an analytical decision-making model was built in MS Excel, which allows to provide pharmacoeconomic analysis and analysis of the budget impact of acalabrutinib in comparison with the combination of venetoclax with obinutuzumab in the first line of therapy for high-risk CLL, as well as acalabrutinib and the combination of venetoclax with rituximab in the treatment of high-risk relapses and refractory forms of CLL. The model took into account only direct medical costs per patient (drug therapy costs).

Results. The “cost minimization” analysis showed that the use of the drug acalabrutinib in the 1st line and for the treatment of relapses and refractory forms of high-risk CLL is the preferred option compared to comparators, having comparable efficacy and lower cost. The cost reduction in the first-line therapy of high-risk CLL and the treatment of relapses and refractory forms of high-risk CLL compared with ibrutinib amounted to 0.8 million rubles or 15.4%, in the first-line therapy of high-risk CLL compared with the combination of venetoclax + obinutuzumab – 1.2 million rubles or 21.0%, in the treatment of relapses and refractory forms of high-risk CLL in comparison with the combination of venetoclax + rituximab – 0.9 million rubles or 17.6%. Budget impact showed that in the case of initiation of first-line acalabrutinib and treatment of relapses and refractory forms in high-risk CLL patients, the burden on the health care system budget can be reduced by 0.813 billion rubles or 16.0% for 1 year of therapy and by 1.219 billion rubles or 9.1% over 3 years of therapy, taking into account only the costs of drugs.

Journal of Modern Oncology. 2021;23(4):612-620
pages 612-620 views

Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review

Valiev T.T., Semenova V.V., Ikonnikova A.Y., Petrova A.A., Belysheva T.S., Nasedkina T.V.


Methotrexate (MTX) is one of the main chemotherapeutic agents that has determined the high effectiveness of protocols for the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphomas. The reverse side of the high anti-tumor activity of MTX is the adverse reactions, which require accompanying preventive therapy. But even modern accompanying therapy in some cases does not avoid severe toxicity from the skin and mucous membranes, nervous system, kidneys, liver. MTX pharmacokinetics exhibits significant individual variability, which may be a reflection of genetic variability. Numerous pharmacogenetic studies have evaluated the effect of polymorphism of various genes involved in MTX metabolism on MTX pharmacokinetics and the development of toxic manifestations in order to improve patient outcomes and decrease drug toxicity. This review presents impact of key metabolic MTX genes (ATIC, DHFR, GGH, FPGS, MTHFR, MTR, MTRR, TYMS) and transporter proteins genes (ABCB1, ABCG2, ABCC2, ABCC4, SLC19A1, SLCO1B1) in the development of MTX side effects. Polymorphic markers in SLCO1B1 gene have the most influence with MTX pharmacokinetic.

Journal of Modern Oncology. 2021;23(4):622-627
pages 622-627 views

Epidemiology and status of specialized medical care for patients with cutaneous T-cell lymphomas: A survey of 163 patients of Russian Federation

Kubanov A.A., Karamova A.E., Bogdanova E.V., Znamenskaya L.F., Vorontsova A.A.


Background. In the Russian Federation, there are currently no official statistical data concerning the incidence of cutaneous T-cell lymphomas (CTCL) and the prevalence of CTCL due to the absence of isolation rubrics in the headings of lymphoproliferative diseases of the federal state statistical observation of the separate neologies.

Aim. To obtain and analyze the results of the number of patients with CTCL (mycosis fungoides and Sézary syndrome) who were on the dispensary observation in medical organizations of dermatovenereological profile in the period 2015 to 2020, the demographic and clinical-epidemiological characteristics, the applied methods of diagnosis and the therapy.

Materials and methods. To conduct the study, the questionnaire was developed to obtain the information of the number of patients observed with diagnoses of "mycosis fungoides" and "Sézary syndrome" in medical organizations of the dermatovenereological profile of the Federal Subjects of the Russian Federation in the period 2015-2020, were researched the demographic characteristics, the diagnostic methods and the therapy in the studied group of patients.

Results. From 24 Federal Subjects of the Russian Federation were obtained the data concerning 163 patients with CTCL under the observation in medical organizations in the period 2015–2020. From 35 Federal Subjects of the Russian Federation the information showed the absence of patients with CTCL under the observation in medical organizations of dermatovenereological profile. We did not receive the data from 10 Federal Subjects of the Russian Federation. Among 163 patients in 144 (89%) were diagnosed mycosis fungoides, in 17 (10%) – Sézary syndrome and in 2 (1%) patients were diagnosed other variants of CTCL. The data concerning the demographic characteristics, the diagnosis and the therapy of CTCL were obtained in 155 of 167 patients. We showed that in 44% of cases, the disease was detected by dermatovenerologists, and the diagnosis was most often (39%) determined by oncologists. In 49% of cases the diagnosis was determined only on the basis of the results of histological study, the immunohistochemical study and the polymerase chain reaction were used in 33% and in 3% of cases, respectively. From 155 patients, 52% were under dispensary observation by oncologists, 41% by hematologists, 26% of patients were observed by dermatologists; 99 patients were under dispensary observation by only one specialist: 50 (32%) of patients – by oncologist, 40 (26%) of patients – by hematologist, 9 (6%) of patients – by dermatovenerologist. Nine (6%) of patients were under dispensary observation by three specialists. The information concerning the therapy was available in 92 (59%) of 155 patients. The most commonly applied method of treatment was chemotherapy – 72%, phototherapy was received by 26%, the same percentage (18%) was received in two groups: the application of interferon α2b and the application of methotrexate, 1% of patients received radiation therapy. The lethal outcome was registered in 53 (34%) patients. Median duration of the disease from the time of diagnosis to death was 3.5±5.0 years, the median – 2 years, the mode – 1 year.

Conclusion. For the first time, the attempt was made to summarize the data of the number of patients with CTCL, to describe the demographic, clinical and epidemiological characteristics, the data concerning diagnostics and the therapy. The obtained preliminary results are required further detailing investigation in close cooperation with the professional specialists such as hematologists and oncologists.

Journal of Modern Oncology. 2021;23(4):628-634
pages 628-634 views

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review (Russian Translation of Cochrane Plain Language Summary)


This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Desborough MJR, Hadjinicolaou AV, Chaimani A, Trivella M, Vyas P, Doree C, Hopewell S, Stanworth SJ, Estcourt LJ. Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review. Cochrane Database of Systematic Reviews 2016, Issue 10. Art. No.: CD012055. DOI: 10.1002/14651858.CD012055.pub2

Journal of Modern Oncology. 2021;23(4):635-636
pages 635-636 views

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation (Russian Translation of Cochrane Plain Language Summary)


This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Crighton GL, Estcourt LJ, Wood EM, Trivella M, Doree C, Stanworth SJ. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database of Systematic Reviews 2015, Issue 9. Art. No.: CD010981. DOI: 10.1002/14651858.CD010981.pub2

Journal of Modern Oncology. 2021;23(4):636-637
pages 636-637 views

Surgical treatment of recurrent ovarian cancer: A review

Egenov O.A., Stilidi I.S., Tyulyandina A.S.


Aim. To analyze the data available in the modern literature on the role of repeated cytoreduction in the complex treatment of relapses ovarian cancer (OC).

Materials and methods. Sources were searched in the following systems Clinicaltrials.gov, PubMed, Medline, NCCN, Scopus, Gynecol Oncol, Elibrary. After analyzing the literature review, 31 sources were used, published from January 1989 to December 2020.

Results. The main method of treatment relapses of ОС is administration of systemic chemotherapy. The role of surgical treatment has been actively discussed for several decades. According to the available data of retrospective, prospective, randomized trials, performing surgery following chemotherapy had a favorable effect on the long-term results of treatment just in case of achieving complete cytoreduction in comparison with only chemotherapeutic treatment of platinum-sensitive recurrence of ОС. A validated prognostic model helps to perform the selection of suitable patients for surgical treatment, therefore, the correct selection for secondary cytoreduction allows to identify the patients with a high chance of achieving сomplete cytoreduction, which reduces the number of ineffective operations in patients with residual tumors.

Conclusion. Complete cytoreduction of all macroscopically detectable recurrent tumor lesions in combination with subsequent systemic chemotherapy leads to an improvement in progression-free survival and life expectancy in a carefully selected group of patients with platinum-sensitive recurrent OC. Secondary cytoreduction in platinum-refractory and platinum-resistant relapses deteriorates the prognosis and doesn't lead to an increase in survival rates. Patient selection is the key point in secondary cytoreductive surgery. The choice of the methodology of selection of patients is in the process of discussion. When planning treatment, all patients with recurrent OC should be discussed at multidisciplinary teams with the participation of specialists in related specialties. Considering a surgical treatment option should be performed it in large centers with extensive experience in the surgical treatment of OC, relapses, performing complex multi-organ resections.

Journal of Modern Oncology. 2021;23(4):638-644
pages 638-644 views

Endoscopic esophageal stenting in combination with chemoradiation therapy: A review

Ivanov A.I., Popov V.A., Burmistrov M.V.


Esophageal stenting is undoubtedly an effective method of choice for resolving malignant dysphagia in the presence of esophageal cancer. Nevertheless, the implantation of esophageal stents for malignant pathology is only a way to achieve adequate oral nutrition, which, unfortunately, does not increase the life expectancy in incurable patients. Early studies on the combination of chemoradiation therapy and stent implantation reported a relatively high rate of complications. Therefore, such therapeutic combinations have not been introduced into widespread practice. Nevertheless, to date, there is no convincing clinical data on the results of a combination of stenting methods and chemoradiation therapy, as well as their effect on the incidence of possible complications. Recent research has shown a very encouraging prospect. The combination of these techniques can increase life expectancy in incurable patients through continuous improvements in stent materials and designs.

Journal of Modern Oncology. 2021;23(4):645-648
pages 645-648 views

Comparative analysis results of surgical treatment, chemoradiotherapy and chemotherapy with assessment of prognostic factors in cervical esophageal cancer

Radzhabova Z.A., Kotov M.A., Girshovich M.M., Ponomareva O.I., Tkachenko E.V., Mitrofanov A.S., Radzhabova M.A., Levchenko E.V.


Aim. To analyze the results of treatment and prognostic factors of survival in patients with cervical esophageal cancer (CEC) who received surgical treatment, chemoradiation therapy and chemotherapy.

Materials and methods. The retrospective study included patients with a verified diagnosis of CEC treated at the Petrov National Medicine Research Center of Oncology from 2009 to 2018 and divided into three treatment groups: surgical treatment, chemoradiotherapy and chemotherapy. The endpoints of the study were overall survival (OS) and relapse-free survival (RFS).

Results. Ninety-seven patients were included in the study: 48 in the surgical group, 30 in the chemoradiotherapy group and 17 patients in the chemotherapeutic treatment group. The average age of patients was 59.2±10.4 years. The median OS in the surgical group was 39.1 months, in the chemoradiotherapy group – 23.9 months and 8.9 months in the chemotherapy group; the overall 3-year survival rate was 51.0% (95% CI 36.4–71.7), 44.9% (95% CI 26.9–74.9) and 26.0% (95% CI 9.9–68.2), respectively. The overall 5-year survival rate for the surgical group and the chemoradiotherapy group was 40.0% (95% CI 25.8–62.0), and 44.9% (95% CI 26.9–74.9), respectively. The presence of coronary heart disease is associated with a significant decrease in OS. The median disease-free survival in the surgical group was 19 months, in the chemoradiotherapy group – 11.5 months and 3.4 months in the chemotherapy group; the relapse-free 3-year survival rates were 44.1% (95% CI 30.2–64.4), 25.0% (95% CI 11.7–53.4) and 14.3% (95% CI 4.0–51.5), respectively. The relapse-free 5-year survival rate for the surgical treatment group and the chemoradiotherapy group was 34.6% (95% CI 21.6–55.3), and 25.0% (95% CI 11.7–53.4). The presence of peptic ulcer disease was statistically significantly associated with higher overall and RFS regardless of the treatment received.

Conclusion. In our study, surgical treatment of the CEC showed better overall and RFS rates compared with chemoradiotherapy. The presence of coronary heart disease and peptic ulcer disease are prognostic factors for overall and RFS.

Journal of Modern Oncology. 2021;23(4):649-654
pages 649-654 views

Influence of retroelements on oncogenes and tumor suppressors in carcinogenesis: A review

Mustafin R.N.


Analysis of scientific literature data has revealed several ways in which retrotransposons, when activated, are involved in carcinogenesis. First, retroelements can encode oncogenic proteins. For example, the Np9 protein is translated from HERV-K endogenous retrovirus transcript. Second, retroelements are used as alternative promoters of protooncogenes. Accordingly, their activation contributes to the enhanced expression of oncogenes (e.g. CSF1R, IRF5, MET, RAB3IP, CHRM3). Third, retroelements are located in the introns of some genes, and upon their activation, they form chimeric transcripts, such as LTR2-FABP7, LTR-ALK, LTR-ERBB4, LINE1-MET, which have pronounced oncogenic activity. Fourth, retroelements are transposed into tumor suppressor genes (e.g. APC, NF1, MSH2, PTEN, RB1, TSC2, STK11, VHL) and inactivate them, which is associated with the presence of hot spots of insertional mutagenesis in them. As a result, the growth of tumors and the survival of their cells are stimulated. It is important to note that protein products of tumor suppressor genes, such as TP53, RB1, VHL, BRCA1, ATM, are characterized by the ability to inhibit the activity of retroelements. Accordingly, when even one oncosuppressive gene is inactivated, a kind of "vicious circle" can be triggered when the control of expression of retroelements is weakened. The latter, in turn, inactivate other tumor suppressors containing hot spots of insertional mutagenesis. This stimulates new pathways of carcinogenesis and the production of oncogenes associated with transposons. Thus, it is possible to explain in a new way the mechanisms of tumor formation in hereditary tumor syndromes. This is due to the fact that the weakening of the function of an oncosuppressor in a germinal heterozygous mutation may be sufficient to trigger a “vicious circle” involving retroelements, oncogenes and other oncosuppressors. Similar mechanisms are likely for sporadic malignant tumors. However, the initiating event in them can be the direct activation of transposons under the influence of stressors, chemical and physical carcinogens. In addition to the events described, activation of retroelements causes genomic instability, which contributes to complex genomic rearrangements often observed in malignant tumors. MicroRNAs and long noncoding RNAs, the sources of which are retroelements, also play an important role in the evolution of tumors. Their study is promising for the development of targeted therapy for neoplasms.

Journal of Modern Oncology. 2021;23(4):666-673
pages 666-673 views

Solitary fibrous tumor: features of the clinical course, radiation and laboratory diagnostics, therapy: A review

Kozlov N.A., Tsygankova A.V., Abdullaev A.G.


Solitary fibrous tumor (SFT) is a relatively rare mesenchymal neoplasm, mainly affecting serous membranes and soft tissues.It is distinguished by a long-term course, a variable risk of metastasis, the possibility of occurrence in any anatomical region, as well as a low-specific histological structure.Moreover, the last two features of SFT are the main causes of diagnostic errors in morphological verification of a neoplasm. Despite the fact that in the twentieth century SFT was mentioned in the scientific literature quite rarely and, as a rule, in the form of single observations, in the last two decades, due to the widespread use of new molecular genetic research methods and the identification of specific mutations in mesenchymal tumors, the quality and accuracy have significantly increased. making a diagnosis. In addition, the clinical observations accumulated in recent decades in a considerable number of cases made it possible to assess in more detail the clinical and morphological parameters of the SFT associated with the risk of local recurrence and the appearance of distant metastases. This article analyzes the modern literature on epidemiology, molecular pathology, features of radiation and morphological diagnostics, aspects of the genesis of solitary fibrous tumor, as well as the choice of optimal treatment for patients.

Journal of Modern Oncology. 2021;23(4):655-659
pages 655-659 views

Activation of the PI3K-AKT-mTOR cascade in uterine leiomyosarcoma: a retrospective study of 31 patients

Rozonova O.A., Artamonova E.V., Kozlov N.A., Delektorskaya V.V., Egorova A.V., Stilidi I.S.


Background. Taking into account the literature data, the activation of the PI3K-AKT-mTOR cascade plays a role in the development of leiomyosarcoma (LMS), and the expression of markers of this signaling pathway in the tumor is associated with a more aggressive course of the disease. In addition, there is some data on the effective use of mTOR inhibitors in LMS.

Aim. To study the frequency of expression of mTOR and phospho-mTOR markers in relapse of high-grade uterine LMS and to evaluate the effect of phospho-mTOR expression on the immediate and long-term results of the use of doxorubicin-containing chemotherapy regimens and the combination of gemcitabine + docetaxel.

Materials and methods. The study included 31 patients with high-grade uterine LMS operated on for relapse. IHC was performed using mTOR and phospho-mTOR antibodies on ready-made histological preparations of the surgical material. The expression level of these markers was estimated as a percentage from 0 to 100%. The immediate and long-term results of the most commonly used drug treatment regimens (doxorubicin-containing regimens and gemcitabine + docetaxel combinations) were analyzed depending on the level of phospho-mTOR expression in the tumor.

Results. The expression of mTOR in the tumor was detected in 4 patients with an expression level from 1 to 2%, and the expression of phospho-mTOR was detected in 20 patients with an expression level from 1 to 70%. Median OS in the group without phospho-mTOR expression was 135 months, in the group with expression – 104 months, p=0.732. When using doxorubicin-containing regimens in the group with phospho-mTOR expression, 12% of patients had a partial response (PR), median PFS was 26.7 months, in the group without expression there was no PR, median PFS was 8.7 months, p=0.67. When using a combination of gemcitabine + docetaxel, in the group with phospho-mTOR expression, 24% of patients had PR, median PFS was 11.1 months, in the group without expression, 14% of patients had PR, median PFS was 12.4 months, p=0.372.

Conclusion. Phospho-mTOR expression was detected in 2/3 of patients with high-grade uterine LMS. There was no effect of the expression of this marker on the OS of all included patients and on PFS in patients who received chemotherapy according to the gemcitabine + docetaxel regime. There was a tendency to an increase in PFS in the group with phospho-mTOR expression in patients who received doxorubicin-containing chemotherapy regimens.

Journal of Modern Oncology. 2021;23(4):660-665
pages 660-665 views

Preliminary assessment of the possibility of using urokinase uPA and urokinase receptor uPAR as universal diagnostic criteria in patients with colorectal and gastric adenocarcinoma

Klimovich P.S., Rubina K.A., Mironov N.A., Kakotkin V.V., Oleynikova N.A., Mal`kov P.G., Kubyshkin V.A., Galliamov E.A., Agapov M.A., Semina E.V.


Background. Lack of universal diagnostic parameters that can accurately and reliably diagnose presence of a malignant neoplasm, anticancer drug effectiveness or metastasis development including dormant ones and also to detect the progression or relapse of the disease at an early stage put on the first place studies related to the identification of such markers. Increased secretion and activity of the urokinase type plasminogen activator (uPA), its receptor (uPAR) accompany many types of malignant neoplasms, contributing their progression and metastasis, as well as the emergence of chemoresistance. So today these proteins are promising diagnostic targets in oncology.

Aim. To evaluate the diagnostic significance of the expression levels of uPA and uPAR in blood serum of patients with colorectal and gastric adenocarcinoma and uPA/uPAR distribution in samples obtained from the primary tumor node, to assess the possibility of their use as universal diagnostic indicators in cancer patients at the stage of primary treatment.

Materials and methods. The study included patients with colorectal and gastric adenocarcinoma in the amount of 50 people and 25 healthy volunteers. The content of uPA and uPAR in blood serum was assessed by enzyme-linked immunosorbent assay, the level of expression of the studied proteins in tumor tissue was assessed using immunohistochemical staining with antibodies to uPA and uPAR.

Results. It was found that in comparison with healthy donors uPA serum concentration was significantly higher in all patients with adenocarcinoma, regardless of gender, and the uPAR content in the blood serum was significantly higher in women. Immunohistochemical staining data showed that the expression of these two proteins in tumor tissue significantly exceeds their expression in normal tissue.

Conclusion. Based on the obtained data the possibility of using uPA in blood serum as a universal diagnostic criterion in patients with colorectal and gastric adenocarcinoma regardless of gender was shown and uPAR in female patients.

Journal of Modern Oncology. 2021;23(4):674-679
pages 674-679 views

Metastatic gastrointestinal stromal tumor of the greater omentum. Case report

Yugay V.V., Nikulin M.P., Mazurenko N.N., Mochal'nikova V.V., Filonenko D.A., Meshherjakov A.A., Bugaev V.E., Arhiri P.P., Stroganova A.M., Stilidi I.S.


Gastrointestinal stromal tumors (GIST) are the most common type of mesenchymal malignancies of the gastrointestinal (GI) tract. Almost 10% of them are originated outside of the GI tract (extra-GIST), while GIST of the greater omentum constitutes about 1% among stromal tumors. More than 80% of GIST have mutations in c-KIT and PDGFRA genes. Herein we demonstrate the case of successful treatment of patient with giant omental GIST with c-KIT exon 11 mutation. 64-years-old woman, was admitted to the Department of abdominal oncology with complaints of shortness of breath and abdominal enlargement in volume. CT-scan revealed a large tumor in the abdominal cavity with tumor size of 54×34×22 cm. The patient underwent left thoraco-abdominal approach. It was found that the tumor was originated from the greater omentum with several metastases located on the peritoneum of the left lateral channel. Resection of the large omentum, splenectomy, liver resection and was done. Postoperative immunohistochemical study showed the expression of CD117, CD34 in tumor cells. Ki-67 index was 12–15%. Genetic study revealed c-KIT exon 11 mutation. Treatment with imatinib 400 mg per day was started. Patient has been treated with imatinib for 12 years. On control examination we have found a metastasis in the anterior abdominal wall 3,5×3×2,5 cm in diameter. Afterwards we performed resection of anterior abdominal wall with metastasis on 9 November 2017. Immunohistochemical study confirmed metastasis of GIST. The index of tumor proliferation activity (Ki-67) was 45%. Patient prolonged imatinib treatment at the dose of 400 mg per day after operation. No signs of progression have been revealed on control examination 72 months after the operation. 12-year progression-free survival during imatinib treatment is unique in our practice. Moreover, in the case of further progression, we have second and third-line targeted therapy (sunitinib and regorafenib) and surgery treatment in local progression.

Journal of Modern Oncology. 2021;23(4):680-684
pages 680-684 views

Targeted therapy of brain metastases in patients with ALK-positive non-small cell lung cancer: A review

Sakaeva D.D., Bulavina I.S.


The data of recent years indicate the steady increase in the frequency of incidence of brain metastases in many localizations of malignant tumors. Non-small cell lung cancer (NSCLC) is the most common cause, that can affect the central nervous system (CNS). The study of prognostic factors for NSCLC patients with brain metastases, the development of prognostic models, and taking into account the molecular changes can help to approach the development of treatment tactics for this category of patients. The main prognostic factors are age, gender, the Karnofsky’/ECOG status, localization and the number of metastatic foci in the brain, the presence of extracranial metastases, and the histological type of tumor. The discovery of driver mutations and stratification of the cohort of patients with lung adenocarcinoma can open up new potential therapeutic effects in this group of patients, both with primary damage of the CNS and with brain metastases against the background of the therapy. The article deals with the analyzing the literature data and the results of international studies in a group of ALK+ NSCLC patients with brain metastases as well as the mechanisms of lung cancer metastases to the central nervous system and the structure of the blood-brain barrier. The comparative analysis of the treatment of this category of patients using third-generation ALK-inhibitors (alectinib, brigatinib, lorlatinib, crizotinib), the frequency of intracranial response and the possible decision-making algorithm in real clinical practice are presented in detail.

Journal of Modern Oncology. 2021;23(4):685-694
pages 685-694 views

Multicenter prospective observational post-approval study of safety and efficacy of bevacizumab (Avegra®, BIOCAD) in patients with metastatic colorectal cancer in real world practice: APOLLON-11 and SOYUZ-APOLLON

Tryakin A.A., Fedyanin M.Y., Moiseenko F.V., Mironov O.V., Stroyakovskiy D.L., Sokolov N.I., Orlova S.A., Mantsyrev E.O., Sultanbaev A.V., Teterich A.A., Babina K.G., Yukalchuk D.Y., Borzyanitsa S.M., Isyangulova A.Z., Saidullaeva A.F., Chernova Y.A., Bobrova E.A., Fadeeva N.V., Chobanu D.Y.


Aim. To evaluate the safety and efficacy of long-term continuous use of Avegra® BIOCAD (international nonproprietary name – INN: bevacizumab) as a targeted therapy in patients with metastatic colorectal cancer in real-world practice.

Materials and methods. The paper presents the interim results of a multicenter prospective observational post-approval study of the safety and efficacy of Avegra® BIOCAD (INN: bevacizumab) combined with chemotherapy in patients with metastatic colorectal cancer. Inclusion criteria: histology verified diagnosis of metastatic colorectal cancer; therapy with bevacizumab (by JSC BIOCAD, Russia) to all patients included in the study, as part of real-world clinical practice, at a dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks in combination with standard cytotoxic regimens (FOLFOX 6, XELOX, etc.). The main safety criteria are the incidence of adverse reactions to bevacizumab and the rate of treatment withdrawal due to the development of adverse reactions to bevacizumab. Additional criteria are objective response rate (complete and partial response to therapy), disease control rate (ORR and stable disease), and rate of disease progression.

Results. At the time of the interim analysis, 441 patients with metastatic colorectal cancer in 28 research centers of the Russian Federation (Moscow, Saint Petersburg and regional clinics) were included in the study. Median age of patients is 62 (28–87) years. Patients had an ECOG performance status of 0–1, with a median follow-up of 7.3 months. After the therapy, the disease control rate was 79.5%. The median PFS was 8 months (95% CI 7.04 to 9.00). The median OS was not reached. Toxicity associated with bevacizumab manifested predominantly as arterial hypertension (3%), diarrhea (1,1%) and asthenia (0.9%). Nine (2.1%) SARs were observed; three (0.6%) of them (COVID-19, intestinal obstruction, multiple organ failure) resulted in mortality. The obtained results are well consistent with the previously known bevacizumab safety profile characteristics.

Conclusion. The interim analysis results confirm the favorable safety profile and high efficacy of Avegra® BIOCAD (INN: bevacizumab) combined with standard cytotoxic regimens (FOLFOX, XELOX, etc.) as first-line therapy in patients with metastatic colorectal cancer. The real-world data for ORR and PFS are comparable with clinical trials results. At the time of the interim analysis publication, the study is ongoing. Final conclusions on the safety and efficacy of bevacizumab (by JSC BIOCAD, Russia), will be made after the study is completed.

Journal of Modern Oncology. 2021;23(4):695-702
pages 695-702 views

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