Vol 22, No 1 (2020)

CLINICAL ONCOLOGY

Solitary (extramedullary) plasmocytoma. Clinical recommendations

Falaleeva N.A., Terekhova A.I., Ptushkin V.V., Osmanov E.A., Poddubnaya I.V., Nevol’skikh A.A., Ivanov S.A., Khailova Z.V., Gevorkian T.G.

Abstract

Solitary (extramedullary) plasmocytoma. Clinical recommendations

Journal of Modern Oncology. 2020;22(1):7-15
pages 7-15 views

Hairy cell leukemia. Clinical recommendations

Al’-Radi L.S., Baikov V.V., Kovrigina A.M., Krivolapov I.A., Moiseeva T.N., Nikitin E.A., Pivnik A.V., Stadnik E.A., Nevol’skikh A.A., Ivanov S.A., Khailova Z.V., Gevorkian T.G.

Abstract

Hairy cell leukemia. Clinical recommendations

Journal of Modern Oncology. 2020;22(1):16-30
pages 16-30 views

ELEVATE-TN Study. New data of acalabrutinib in first-line treatment of chronic lymphocytic leukemia. Resolution

Poddubnaya I.V., Al-Radi L.S., Byalik T.E., Kaplanov K.D., Molostvova V.Z., Nikitin E.A., Pospelova T.I., Ptushkin V.V., Samoilova O.S., Stadnik E.A., Tumyan G.S.

Abstract

Over the past decade, we have seen a significant change in modern approaches in the first-line treatment of chronic lymphocytic leukemia (CLL). The CLL-10 study data established the FCR regimen as the treatment of choice for younger patients with limited comorbidities, while for patients older than 65 years, the BR regimen is more often considered as less toxic one. According to published data, 46% of patients with newly diagnosed CLL have comorbidities. Moreover, high-risk patients with del(17p) and/or TP53 mutation do not have response on immunochemotherapy (ICT) most often. Thus, about 1/2 of the patients cannot be treated or will not respond to standard ICT regimens. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors is an important option of the first-line treatment of patients with CLL. Acalabrutinib is a highly selective second-generation BTK inhibitor that does not inhibit EGFR, ITK or TEC targets. Acalabrutinib in combination with obinutuzumab or as monotherapy can be considered as a highly effective and safe option of the first line of CLL therapy. Based on the hight selectivity of the agent, acalabrutinib can be considered as the preferable option for patients who are not eligible for ICT, including patients with commodities, such as cardiovascular diseases or risk factors for their development.

Journal of Modern Oncology. 2020;22(1):31-33
pages 31-33 views

Surgical treatment of trophoblastic disease. Modern concept and contradictions (literature review)

Maslennikov A.F., Meshcheriakova L.A., Kuznetsov V.V., Kozachenko V.P., Komarov I.G.

Abstract

A review of studies on the comparison of the effectiveness of surgical treatment of malignant trophoblastic tumors before the start of standard chemotherapy and in terms of combination treatment is presented. According to Russian and foreign studies, surgical treatment is relevant for patients with primary or metastatic tumor resistance. The article presents the results of treatment of patients after various types of operations. The most common volume of surgery was a hysterectomy. The article also discusses the results of treatment of benign forms of trophoblastic disease. Surgical treatment of a malignant trophoblastic tumor before the start of standard chemotherapy was performed according to vital indications or in connection with a tumor determined by imaging methods. And the analysis carried out in Blokhin National Medical Research Center of Oncology showed expected prognoses for patients who underwent surgical treatment prior to the start of standard chemotherapy regimens. Such patients were admitted to the clinic with a resistant or disseminated form of the tumor. During their treatment, high-dose chemotherapy or additional surgical interventions were required, which significantly worsened the prognosis of the disease. In the opposite case, when removing a localized resistant primary tumor or its metastasis, in the postoperative period, chemotherapy was not carried out in connection with marker remission.

Journal of Modern Oncology. 2020;22(1):34-39
pages 34-39 views

Possibilities of per-oral transpapillary cholangioscopy in oncological practice

Yurichev I.N., Timofeev M.E., Malikhova O.A., Savosin R.S.

Abstract

Relevance. Diagnosis of malignant diseases causing bile duct strictures is a big challenge. At admission, patients with suspected biliary tract stricture, initially undergo endoscopic retrograde cholangiopancreatography (ERCP) as a diagnostic and treatment method. The morphological diagnosis of bile duct stricture based on ERCP with brush biopsy or intraductal forceps biopsy is limited by their low sensitivity. Consequently, a significant proportion of strictures remains undiagnosed, which led to the development of methods based on cholangioscopy.

Aim. To determine the role of per-oral transpapillary cholangioscopy (TCS) in a specialized cancer clinic.

Materials and methods. SpyGlass direct visualization system for per-oral intraductal examination from Boston Scientific was clinically tasted in Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. Using this electronic system, TCS was performed in 4 patients with various malignant diseases.

Results. In all cases, TCS was successful. In all patients, the diagnosis was confirmed with a forceps intraductal biopsy using Spybite forceps.

Conclusion. Single-use electronic direct visualization system for per-oral intraductal examination and interventions like SpyGlass can be recommended for use in specialized cancer centers.

Journal of Modern Oncology. 2020;22(1):40-45
pages 40-45 views

Modern view on the issues of diagnosis and verification of axillary lymph nodes involvement in early breast cancer

Kolyadina I.V., Danzanova T.Y., Khokhlova S.V., Trofimova O.P., Kovaleva E.V., Rodionov V.V., Poddubnaya I.V.

Abstract

The involvement of axillary lymph nodes is one of the most important prognostic factors, significantly affecting the treatment strategy for early breast cancer (BC). The risk of axillary lymph node metastases depends directly on a number of factors (age of women, size of tumor, presence of lymphovascular invasion and biological characteristics of cancer). The evaluation of regional lymph node status in patients with early BC includes the clinical examination of regional zones and the ultrasound study (US), using these methods can help to study lymph nodes shape, borders, margins and structure. The sensitivity of ultrasound in the evaluation of regional lymph nodes status directly depends on the biological subtype of the tumor; the minimum level of ultrasound sensitivity in the evaluation of lymph nodes status is detected for luminal HER2-negative cancer (less than 40%), and maximum sensitivity is detected for triple negative and HER2-positive subtypes (68–71%). Clinical examination and modern ultrasound are the most accessible methods for the evaluation of regional lymph nodes status, but the possibility to misjudge metastatic process can be detected in 1/4 of patients. Verification of the diagnosis in the preoperative phase (fine-needle aspiration biopsy/core-needle biopsy under ultrasound guidance) allows minimize the number of errors for the regional staging. The sentinel lymph node biopsy (SLNB) is the «gold standard» of regional treatment in patients with early stage BC, nowadays. The randomized trials (NSABP B-32, ACOSOG q0011) show the safety of recession of performing regional lymph node dissection in favor of SLNB not only in case of clinically negative lymph nodes, but also in patients with metastases in ≤2 sentinel lymph nodes, upon condition that organ-conservative treatment and subsequent radiation therapy will be used. High-quality regional staging, the choice of the therapeutic algorithm in accordance with the biological characteristics of carcinoma, the application of the most effective modern drug regimes, the optimal radiation therapy allow not only minimize the extent of surgery, but also achieve high long-term survival results, provide excellent functional results and high quality of life in patients with the involvement of axillary lymph nodes.

Journal of Modern Oncology. 2020;22(1):46-52
pages 46-52 views

The efficacy of the combination of eribulin and trastuzumab in advanced HER2-positive breast cancer: the results of Russian observational study

Kovalenko E.I., Artamonova E.V., Karabina E.V., Andreiashkina I.I., Prokof’eva E.A., Popova N.O., Gaisina E.A., Evstigneeva I.V., Shaidorov M.V., Zhiliaeva L.A., Ponomarenko D.M., Khasanova A.I., Mukhametshina G.Z., Koziakov A.E., Vorotilina L.V., Povyshev A.I., Simolina E.I., Marfutov V.V., Kozlov D.V., Suslova I.R., Shikina V.E., Karandeeva T.V., Shepel’ A.O., Kramskaia L.V., Oskirko D.A., Frolova O.S.

Abstract

The article presents the experience of 19 Russian medical institutions on the use of eribulin in combination with trastuzumab in various treatment lines of metastatic HER2+ breast cancer in routine clinical practice.

Aim. The main objective of this retrospective observational study was to evaluate the efficacy and tolerability of eribulin and trastuzumab combo in HER2+ breast cancer patients pretreated with anthracyclines and taxanes. The analysis included 60 patients who received at least 2 cycles of eribulin in combination with trastuzumab. 2 patients (3.3%) received treatment as the 1st line, as the 2nd – 14 (23.3%), as the 3rd – 16 (26.7%), and as the 4th and more – 28 (46.7%).

Materials and methods. Complete response was achieved in 2 (3.3%) patients, partial response in 9 (15%), stable disease in 33 (55%), stabilization for more than 6 months in 11 (18.3%), disease progression was detected in 16 (26.7%) patients. The objective response rate was 18.3% in the whole group, the clinical benefit rate – 36.7%.

Results. The objective response rate in the group of the luminal subtype (ER/PR+HER2+) was 26.9%, in HER2-overexpressed subtype (ER-PR-HER2+) – 8.8% and 64.7%, respectively, disease progression was recorded 2.3 times more often – 35.3% versus 15.5% in the luminal subtype group. The median progression-free survival in patients with HER2+ breast cancer was 4.95 months (95% confidence interval – CI 3.04–8.29 months), in luminal subtype – 6.38 months (95% CI 3.33–8.54 months), in non-luminal – 4.44 months (95% CI 2.4–7.96 months); p=0.306. The treatment was well tolerated, the spectrum of adverse events corresponded to the eribulin toxicity profile.

Conclusions. The uniqueness of this study lies in the fact that on a large clinical material from the standpoint of real clinical practice, a very promising treatment regimen that is not used routinely in a number of countries has been studied, its effectiveness and satisfactory tolerance have been confirmed.

Journal of Modern Oncology. 2020;22(1):53-59
pages 53-59 views

The effect of local immunity on gastric cancer prognosis

Khakimova G.G., Tryakin A.A., Zabotina T.N., Borunova A.A., Malikhova O.A., Juraev F.M., Peregorodiev I.N., Zaharova E.N., Tabakov D.V.

Abstract

Aim. To study the state of local immunity in patients with gastric adenocarcinoma.

Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 with stage I–III, 20 with stage IV) received surgical/combined treatment or chemotherapy, respectively, at the Blokhin Scientific Research Center of Oncology. Tumor tissue was taken before treatment. By using flow cytometry there were evaluated the percentage of tumor tissue infiltration by lymphocytes (CD45+CD14-TIL); T cells (CD3+CD19-TIL); B cells (CD3-CD19+TIL); NK cell (CD3-CD16+CD56+TIL); effector cells CD16 (CD16+Perforin+TIL) and CD8 (CD8+Perforin+TIL) with their cytotoxic potential – active CD16TIL and active CD8TIL; subpopulations of regulatory T cells – NKT cells (CD3+CD16+CD56+TIL), regulatory cells CD4 (CD4+CD25+CD127-TIL) and CD8 (CD8+CD11b-CD28-TIL). The prognostic value of immune cells for overall survival (OS) and progression-free survival (PFS) was assessed.

Results. A favorable prognosis factor for progression-free survival in patients with local and locally advanced forms of gastric cancer was an increase in the number of CD3-CD19+TIL (HR 0.862, 95% CI 0.782–0.957, p=0.005), and an unfavorable prognosis was an increase in NK cells (CD3-CD16+CD56+TIL); HR 1.382, 95% CI 1.087–1.758, p=0.008. The negative effect of the relative content of NK cells (CD3-CD16+CD56+TIL) and NKT cells (CD3+CD16+CD56+TIL) on OS of patients with metastatic gastric cancer noted (HR 1.249, 95% CI 0.997–1.564, p=0.053; HR 1.127, 95% CI 1.025–1.239, p=0.013). At the same time, an increase in the percentage of tumor tissue infiltration by lymphocytes (CD45+CD14-TIL) and an increase in the age of patients (HR 1.005, 95% CI 1.002–1.008, p=0.003; HR 1.098, 95% CI 1.031–1.170, p=0.004) reduce the incidence of PFS in patients with metastatic gastric carcinoma.

Conclusion. Indices of local immunity can serve as additional prognostic factors for gastric carcinoma.

Journal of Modern Oncology. 2020;22(1):60-65
pages 60-65 views

Treatment of children with medulloblastoma without metastatic involvement in the age group older than 3 years: international experience and results of intercenter trial

Levashov A.S., Zagidullina S.R., Stroganova A.M., Khochenkov D.A., Ryzhova M.V., Gorelyshev S.K., Kadirov S.U., Babelyan S.S., Grigorenko V.A., Sidel’nikov D.A., Subbotina N.N., Daylidite V.V., Mentkevich G.L.

Abstract

Background. During the past 20 years, some large international studies have been conducted that evaluated the effectiveness of treatment programs for children with medulloblastoma. At the same time, in the standard risk group, fairly high rates of 5-year overall survival (OS) and event-free survival (EFS) were achieved, which amounted to 85% and 80%, respectively. At the present time some risk-adaptive therapeutic programs are developed according to molecular-biological features of tumor cells and possibility of chemotherapy and craniospinal radiation (CSI) therapy dose reduction.

Materials and methods. From 2008 to 2018 fifty one pediatric patients with primary diagnosed medulloblastoma in the age group 3–18 years were included in trial, 38 in standard risk group, 13 in high risk group (without metastatic disease). Treatment program consisted of surgical removal of the primary tumor site with subsequent chemotherapy (with high-dose cyclophosphamide or thiophosphamide) and radiation therapy (with CSI of 23.4 Gy or 36 Gy, depending on the risk group). In order to detect morphological and molecular biological distinctive features of tumor cells, the following criteria were evaluated: histological variant, molecular subgroup, methyltransferase status by DNMT and MGMT proteins expression, presence of C-MYC/N-MYC gene amplification, Iso17q and TP53 gene mutation.

Results. As a result of this study, sufficiently high rates of overall survival and progression/relapse-free survival (PRFS) were achieved in standard and high-risk groups patients, which amounted to 76.0±8.8% and 83.3±10.8% with median follow-up 62.9±6.2 months and 52.2±7.8 months, respectively. There was revealed patients group in the age 3–7 years with 100% PRFS and median follow-up 66.9±8.9 months. At the same time, morphological and molecular biological factors of an unfavorable outcome of the disease were absent in the tumor samples (large cell – anaplastic histology, C-MYC/N-MYC gene amplification, Iso17q and TP53 gene mutation). We have also achieved 100% PRFS in patients with desmoplastic tumor histology and in patients, who were treated with thiphosphamide-based chemotherapy regimen. Molecular-biological characteristics analysis of tumor cells showed a negative effect on PRFS of DNMT-positive status (Score >4, by 3 markers) and presence of N-MYC gene amplification (SHH molecular subgroup).

Conclusion. There was identified a group of patients aged 3 to 7 years, for whom the possibility for reducing of CSR dose down to 18 Gy opens. Understanding of tumor cells methyltransferase status creates the prerequisites for using of epigenetic demethylating therapy. It is necessary more observations to assess the effect of the chemotherapy regimen with high-dose thiophosphamide on the PRFS.

Journal of Modern Oncology. 2020;22(1):66-76
pages 66-76 views


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