Vol 23, No 1 (2021)

CLINICAL ONCOLOGY
Breast cancer
Zhukova L.G., Andreeva I.I., Zavalishina L.E., Zakiriakhodzhaev A.D., Koroleva I.A., Nazarenko A.V., Paltuev R.M., Parokonnaia A.A., Petrovskii A.V., Portnoi S.M., Semiglazov V.F., Semiglazova T.I., Stenina M.B., Stepanova A.M., Trofimova O.P., Tyulyandin S.A., Frank G.A., Frolova M.A., Shatova I.S., Nevol’skikh A.A., Ivanov S.A., Khailova Z.V., Gevorkian T.G.
Abstract

Breast cancer (BC) is a malignant tumor originating from the epithelium of the breast tissue. There is no single etiological factor in the development of breast cancer. In 3–10% of patients with breast cancer, the development of the disease is associated with the presence of mutations in the breast cancer gene (BRCA) 1, BRCA2, CHEK, NBS1, TP53. In other patients, breast cancer is sporadic.

Journal of Modern Oncology. 2021;23(1):5-40
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Second-line systemic therapy for metastatic colorectal cancer (Russian Translation of Cochrane Plain Language Summary – PLS)
Abstract

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Mocellin S, Baretta Z, Roqué i Figuls M, Solà I, Martin-Richard M, Hallum S, Bonfill Cosp X. Second-line systemic therapy for metastatic colorectal cancer. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD006875. DOI: 10.1002/14651858.CD006875.pub3.

Journal of Modern Oncology. 2021;23(1):42-42
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Systemic treatments for metastatic cutaneous melanoma (Russian Translation of Cochrane Plain Language Summary – PLS)
Abstract

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Pasquali S, Hadjinicolaou AV, Chiarion Sileni V, Rossi CR, Mocellin S. Systemic treatments for metastatic cutaneous melanoma. Cochrane Database of Systematic Reviews 2018, Issue 2. Art. No.: CD011123. DOI: 10.1002/14651858.CD011123.pub2

Journal of Modern Oncology. 2021;23(1):43-44
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Role and place of PARP inhibitors in the modern treatment algorithm of BRCA-associated HER2-negative metastatic breast cancer. Results of the educational and discussion events based on the “OncoForum” platform
Abstract

In 2020, within the framework of the educational project Talisman on BRCA-associated HER2-negative metastatic breast cancer (mBC), Pfizer with the support of TS Oncology held 4 educational and discussion events based on the OncoForum platform (virtual-platform developed and operated by TS Oncology). 44 key specialists from federal and regional cancer centers representing 7 federal districts took part in these events and shared their opinion on the current state of availability of molecular genetic research for germline mutations in BRCA genes and treatment approaches of BRCA-associated HER2-negative mBC in Russia. The results of these interactive discussions are represented in the current overview.

Journal of Modern Oncology. 2021;23(1):45-47
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Piqray – basic questions at the start: whom to test? whom to treat? how to treat? Event review of the satellite symposium. RUSSCO Big Conference «Breast Cancer» (online). January 29th, 2021
Abstract

A Satellite Symposium of Novartis Pharma was held on January 29th, 2021, within the framework of the RUSSCO Big Conference «Breast Cancer». It was dedicated to the diagnostics and treatment of patients with hormone-dependent HER2-negative advanced breast cancer (HR+ HER2- aBC) with a PIK3CA mutation using target drug Piqray (alpelisib). Experts-oncologists discussed the diagnostics of the PIK3CA mutation, data from clinical studies of alpelisib, characteristics of patients who may benefit from the alpelisib, prevention and control of adverse events that may develop during therapy with alpelisib. For planning anticancer therapy using alpelisib in combination with fulvestrant, all patients with HR+ HER2- aBC should be tested for PIK3CA mutation at the first signs of a metastatic process. Data from clinical trials demonstrate that this combination provides approximately 2-fold increase in median progression free survival compared to a placebo + fulvestrant combination. Alpelisib can be prescribed to patients with HR+ HER2- aBC with a PIK3CA mutation after progression on endocrine therapy, in a combined mode. The main adverse events – hyperglycemia and rash – are associated with the mechanism of alpelisib action, and are predictable and manageable.

Journal of Modern Oncology. 2021;23(1):48-52
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Don’t let it disappear: new opportunities to prolong the life of HR+ HER2- advanced breast cancer patients. Event review of the satellite symposium. RUSSCO Big Conference «Breast Cancer» (online). January 28th, 2021
Abstract

Increasing life expectancy and maintaining its quality are the main goals of the hormone-dependent HER2-negative advanced breast cancer (HR+ HER2- аBC) therapy. A Satellite Symposium of Novartis Pharma was held on January 28th, 2021, within the framework of the RUSSCO Big Conference «Breast Cancer». It was dedicated to the benefits of Risarg (ribociclib) therapy in combination with hormone therapy (HT). Experts-oncologists shared current data and their experience with ribociclib. The combination of CDK4/6 inhibitors with HT became a gold standard for the 1st line therapy for HR+ HER2- aBC. And the choice of a specific drug is based on the data of clinical studies and is made taking into account the individual characteristics of the patient. The results of ribociclib studies (MONALEESA-3 and MONALEESA-7) demonstrate a significant increase in the median overall survival and a decrease in the risk of death by 28 and 30%. The tolerance profile of ribociclib is well studied and controlled, therefore the risks of adverse events can be reduced by the competent monitoring, and the necessary dose modification can be made, which allows most patients to maintain highly effective therapy. The use of ribociclib allows to achieve the main goals of therapy – to prolong the patient’s life and maintain or improve its quality.

Journal of Modern Oncology. 2021;23(1):53-60
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The frequency and spectrum of PIK3CA mutations in patients with estrogen receptor-positive HER2-negative advanced breast cancer residing in various regions of Russia
Sokolova T.N., Aleksakhina S.N., Yanus G.A., Sultanbaev A.V., Menshikov K.V., Lysenko A.N., Zukov R.A., Zyuzyukina A.V., Murunova Y.N., Rossokha E.I., Bakharev S.Y., Basova E.A., Kasmynina T.A., Shumskaya I.S., Bakshun Y.I., Musaeva K.S., Khasanova A.I., Dmitriev V.N., Bolieva M.B., Gadzaova C.H., Petrenko O.L., Maksimov D.A., Vladimirov V.I., Goldberg V.E., Popova N.O., Kibisheva M.V., Khamgokov Z.M., Vasilyev A.E., Iyevleva A.G., Imyanitov E.N.
Abstract

Relevance. PIK3CA belongs to the top three most frequently mutated genes in breast cancer (BC), especially in estrogen receptor (ER) positive, HER2 negative BC subtype. With an approval of selective PI3K-alpha inhibitor, alpelisib, this alteration has become actionable in ER+HER2- tumors. The frequency and spectrum of PIK3CA alterations in various cohorts is affected by a number of factors, including the distribution of BC expression subtypes, histological types, patient age, and even ethnicity.

Aim. Aim of the current study was to characterize the frequency and spectrum of PIK3CA alterations in Russian BC patients.

Materials and methods. The analysis of PIK3CA exon 7, 9 and 20 mutations was performed in a cohort of Russian ER+HER2- BC patients by a combination of high-resolution melting analysis, allele-specific PCR, and digital droplet PCR.

Results. PIK3CA lesions were identified in 62/206 (30%) patients. Noteworthy, 59/62 (95%) of the identified variants were represented by the three most common p.E542K, p.E545K, and p.H1047R substitutions. The analysis of clinical and morphological characteristics revealed the trends towards association of PIK3CA mutations with older age and more frequent metastatic lung involvement.

Conclusion. The obtained data on the frequency and spectrum of PIK3CA somatic aberrations can be helpful when organizing molecular genetic testing of breast cancer patients and using PI3K inhibitors in Russian population.

Journal of Modern Oncology. 2021;23(1):61-67
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Analysis of the efficacy and safety of eribulin therapy in patients with HR+/HER2- metastatic breast cancer pretreated with CDK4/6 inhibitors in real Russian practice
Kolyadina I.V., Abidova N.R., Akopyan A.A., Antonova G.V., Arapova O.I., Bobrova E.A., Bolotina L.V., Valiakhmetova C.K., Vasilevskaya A.V., Vladimirova L.Y., Volkonskiy M.V., Ganshina I.P., Gudkova I.E., Dergunov A.S., Evstigneeva I.V., Egurenkova V.S., Emshanov A.V., Zhukova L.G., Zueva E.V., Karabina E.V., Kolokolov J.J., Kuzmicheva S.V., Kuchevskaya O.A., Luev I.A., Maistrenko K.S., Markizova E.V., Marfutov V.V., Medvedev S.P., Merzlikina Y.I., Nersesova T.A., Ovchinnikova E.G., Orlova S.A., Samaneva N.Y., Stativko O.A., Storozhakova A.E., Stroyakovskiy D.L., Sultanbaev A.V., Tekeeva A.I., Fadeeva N.V., Fedorova A.N., Shalaeva O.M., Shangina I.A., Shirokova O.N., Shumskikh A.R., Yakubova M.Z.
Abstract

Relevance. Data on the efficacy of endocrine and chemotherapy regimens in patients with hormone-resistant metastatic breast cancer (mBC) after progression with CDK4/6 inhibitors are limited; the search for an effective therapy regimen in this clinical situation is an urgent task of clinical oncology.

Aim. Evaluate the efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors; compare the results of the Russian study and the EMPOWER observational study in the USA.

Materials and methods. The Russian observational study included 54 patients (pts) with HR+/HER2- mBC, who were treated with eribulin after CDK4/6 inhibitors in 24 Russian Cancer hospitals. The median age of pts was 56 years; 75.9% of them had recurrent BC, 24.1% – de novo BC stage IV; 51.9% of pts had progression with CDK4/6 inhibitors in the first 6 months of therapy (primary endocrine resistance); 48.1% of patients had progression in the period from 6 to 38 months; 89.1% had visceral site of metastases (liver MTS – 65.5%, lung MTS – 52.8%, brain MTS in 7.5%). Eribulin was used after anthracyclines and taxanes in 94.4% of cases. The efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors was studied, as well as subgroup analysis according to age, sites of metastasis, and previously treatment options.

Results. Eribulin was prescribed in the standard regimen of 1.4 mg/m2 on days 1 and 8, the interval between cycles was 21 days, the number cyclys of chemotherapy was 1–44 (median – 8, the mean number of cycles – 10.5). With a median follow-up of 11.5 months (from 3 to 36 months), 30 patients (55.6%) continue therapy with eribulin at present; therapy was cancelled in 24 patients due to progression in 22 (40.7%) cases, and due to intolerable toxicity in 2 (3.7%) patients. The maximum response to eribulin therapy included partial response (in 11 cases, 24.4%), stable disease (in 30 cases, 66.7%) and progression in 4 (8.9%) patients. Median PFS with eribulin therapy was 10.0 months; the 6-month, 1-year, and 2-year PFS were 79.5%, 44.8% and 26.5%, respectively. Eribulin therapy was equally effective in different subgroups (p>0.05) and did not depend on the age of patients, the previously received treatment, the presence of visceral MTS and liver damage. The best response to chemotherapy with eribulin was observed in lung metastases: median PFS 24 months vs 9.1 months, p=0.056. The safety profile was favorable; adverse events were registered in 34.5% of patients, which required dose adjustment in 18.5% of cases. With a median follow-up of 11.5 months, 92.6% of patients remain alive.

Conclusion. Eribulin has demonstrated high efficacy and favorable safety profile in hormone-resistant HER2- mBC in patients with progression when receiving CDK4/6 inhibitor.

Journal of Modern Oncology. 2021;23(1):68-76
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Opportunities for metastatic triple negative breast cancer therapy
Ganshina I.P., Gordeeva O.O., Manukyan M.S.
Abstract

Metastatic triple negative breast cancer (mTNBC) is a difficult task for the chemotherapist in view of the disease aggressiveness, biological heterogeneity of the tumor, as well as the limit of therapy options. The approved modern drugs, such as immunotherapy and PARP inhibitors, have improved the treatment results in women with mTNBC. However, not all women are the candidates for this kind of therapy due to the lack of suitable points of application. In this context, high hopes are placed on the new treatment options currently being studied in clinical trials. The review summarizes data on advanced drugs that have demonstrated their efficacy in this multiplex group of women, but not yet registered at the territory of the Russian Federation Russian Federation, and will allow us to form an idea of the future algorithm of treatment of women with mTNBC.

Journal of Modern Oncology. 2021;23(1):78-81
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Prognostic role of clinical and biological factors and parameters of hormonal profile in patients with primary inoperable HER2-negative breast cancer
Samaneva N.I., Vladimirova L.I., Kolyadina I.V., Frantsiyants E.M., Storozhakova A.E., Bandovkina V.A., Kalabanova E.A., Kabanov S.N., Svetitskaya I.V., Tishina A.V., Ezhova M.O.
Abstract

Relevance. Breast cancer (BC) is among the most common cancers and the leading causes of cancer death in women worldwide. Much attention is paid to the problem of its hormoneresistance; however, the issues of using prognostic markers and predictors in routine cancer clinical practice remain unresolved.

Aim. Study and analysis of prognostic significance of clinical and biological factors and parameters of the hormonal profile in patients with primary inoperable HER2-negative breast cancer receiving neoadjuvant chemotherapy.

Materials and methods. The study included 162 patients with locally advanced primary inoperable HER2-negative breast cancer. Patients were divided into 2 groups. Group 1 included 58 patients with early disease progression within 6 to 12 months after radical surgical treatment. Group 2 included 104 patients with no disease progression within 2 years after radical surgical treatment. In all cases, diagnosis was verified histologically and immunohistochemically. Levels of prolactine, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone, testosterone and cortisol were measured by RIA. The blood plasma values in 20 healthy donors were used as reference one. The data were processed using the Statistica 7.0 and MedCalc (version 9.3.5.0) programs. All patients received combination antitumor treatment according to clinical guidance.

Results. An analysis of the overall (OS) and event-free (EFS) survival in group 1 showed that the median EFS in patients with luminal B BC was 9 months, with triple-negative BC (TNBC) – 8 months. 6-month EFS in luminal B subtype was 87.5%, in TNBC – 79.4%, p=0.37985. 1-year EFS was 1.72±1.7% regardless of the biological subtype. The median OS in luminal B BC was 25 months, in TNBC – 26 months. 1-year OS in luminal B BC – 100%, in TNBC – 93.9%, p=0.138. 2-year OS in luminal B BC – 54.2%, in TNBC – 55.9%, p=0.697. 3-year survival in luminal B BC – 37.5%, in TNBC – 41.2%, p=0.639. An analysis of OS and EFS in group 2 showed that the median EFS was not reached for all biological subtypes. 3-year survival in the group was 100% regardless of the biological subtype. The median OS was not reached for all biological subtypes. 3-year OS in the group was 100%. An analysis of the hormonal profile in the treatment dynamics showed decreased levels of estradiol in all groups of patients (by 1.6 times). In group 1, progesterone was decreased by 2.1 times, testosterone by 2.4 times and LH by 2.1 times in all BC subtypes (p≤0.05). Patients of group 2 showed 2 times reduced cortisol and 3 times reduced prolactin in all BC subtypes, while LH levels were elevated by 1.6 times in luminal A and B BC.

Conclusion. Aggressive course was observed similarly in triple-negative cancer as well as in luminal cancer with primary hormone resistance. Studying of pituitary and sex hormones and cortisol have a great clinical significance in patients with all biological subtypes of BC. This should be taken into account when predicting the course of the disease and developing further treatment options.

Journal of Modern Oncology. 2021;23(1):82-87
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Antiangiogenic therapy for breast cancer with triple negative phenotype
Ganshina I.P., Ivanova K.A., Gordeeva O.O., Arkhipov A.V., Zhukova L.G.
Abstract

Triple-negative breast cancer is 10–24% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

Journal of Modern Oncology. 2021;23(1):88-92
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Actual treatment options for locally advanced and metastatic cutaneous squamous cell carcinoma
Ignatova A.V.
Abstract

Squamous cell carcinoma of the skin, or cutaneous squamous cell carcinoma (CSCC), is the second most frequent type of skin cancer, and its incidence continues to rise all over the world. Usually has a benign clinical behavior, but it can be presented as locally invasive and metastatic aggressive tumor with 2% mortality rate. Nowadays, new risk factors for have appeared, that form pharmacologically-induced CSCC after immunosuppressant drugs used for organ transplantation, or BRAF inhibitors used for melanoma. In recent years we have got a new information about the role of mutational burden, signaling pathways involved in CSCC development and new possibilities and molecules for targeted therapy. Better understanding of the immune system functioning and benefits of immunotherapy with immune checkpoint inhibitors (PD-1) for CSCC that has changed the therapeutic approach. According to recent clinical trials data, new treatment options with PD-1 inhibitors achieved a response rate of 50% for locally advanced CSCC and 47% for metastatic CSCC, including 16.1% complete remissions. This review focuses on the molecular profile, targeted therapies and immunotherapy for locally advanced and metastatic CSCC.

Journal of Modern Oncology. 2021;23(1):94-98
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Endoscopic semiotics of metastatic bronchial tumors
Kontsevaya A.Y., Krylovetskaia M.A., Malikhova O.A., Komarov I.G.
Abstract

Aim. To study the possibilities of bronchoscopy in the detection and evaluation of metastatic lung tumors.

Materials and methods. From 2017 to September 2020, 3719 bronchoscopies, including 1081 biopsies during bronchoscopy were performed at the Blokhin National Medical Research Center of Oncology. According to the results of the morphological verification, 40 patients had been diagnosed with lung metastasis.

Results. Endobronchial metastatic tumors from extrapulmonary malignancies are quite rare. After had studying 40 cases of metastatic bronchial tumors, we found that the most commonly primary malignancies associated with endobronchial metastases were breast cancer (12 patients), colorectal cancer (6 patients) and thyroid cancer (4 patients). All patients who had been diagnosed with the pathology during the bronchoscopy had been required to make a biopsy for the purpose of morphological verification.

Conclusion. The value of bronchoscopy lies in the possibility not only of the detailed visual studying and detecting the tumor pathology of the bronchial tree, but also of obtaining material for morphological analysis. In this regard, the role of biopsy during bronchoscopy is extremely important. In the visual signs of tumor lesion, it is necessary to take multiple biopsies from different parts of the tumor.

Journal of Modern Oncology. 2021;23(1):100-104
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Serous borderline ovarian tumors: modern possibilities of ultrasound diagnostics in monitoring the course of the disease after organ-preserving operations
Davydova I.I., Chekalova M.A., Karseladze A.I., Kuznetsov V.V., Meshcheriakova L.A., Dedy T.V., Cherkasov E.I., Zharova A.S.
Abstract

Relevance. Borderline ovarian tumors (BOT) occur mainly in women of reproductive age and account for 20% of all neoplasms of the female genital organs. Currently, there is an increase in the incidence of ВОТ. One of the reasons for the increase in morbidity is the improvement of knowledge and experience in relation to the morphological diagnosis of tumors of low malignancy potential. Nevertheless, the results of a preliminary instrumental assessment of the nature of the disease and the final diagnosis formed by histological examination are not always satisfactory, since borderline tumors are a thin layer that occupies an intermediate position between benign and malignant tumors. And, in spite of the fact that ВОТ is an independent nosological form in the histological classification, nevertheless, they have signs of both benign and malignant neoplasms. In this regard, the complexity of both instrumental and morphological diagnostics of ВOT becomes understandable, and, therefore, difficulties arise in determining the tactics of treatment, choosing the optimal operation, and the need for drug therapy. All these issues are directly related to the patient’s quality of life, and, most importantly, to survival. Because an incorrectly established diagnosis entails incorrect treatment and unsatisfactory results. Thus, the study of the peculiarities of ВOT diagnostics is extremely important. The ultrasound computed tomography method is simple, relatively cheap and affordable. Considering that almost all patients with ovarian neoplasms undergo this type of examination, it is extremely important and interesting to assess the role of the ultrasound method in the diagnosis of ВОТ. Moreover, at present more and more gynecological oncologists are resorting to organ-preserving surgical interventions for ВOТ. Therefore, it is especially important to study the possibility of ultrasound diagnostics in monitoring the course of the disease after breast-conserving operations, identifying recurrences of the disease in the ovary, differentiating recurrence and cystic formations of the ovaries.

Aim. To determine the effectiveness of computer-assisted ultrasound diagnostics in monitoring the course of BOT after breast-conserving operations.

Materials and methods. At Blokhin National Medical Research Center of Oncology carried out a retrospective and prospective analysis of 405 patients with serous BOT for the period 1970–2013. The age of the patients varied in a wide range, the minimum was 15, the maximum was 78 years, the median corresponded to 38 years. Before the start of treatment, the patients underwent an ultrasound examination (ultrasound) of the abdominal organs, the pelvic organs and the retroperitoneal space. The studies were carried out on expert ultrasonic systems Siemens ACUSON S2000, Hitachi ARIETTA V70 and Philips EPIQ 5.

Results. We studied the capabilities of the ultrasound method for diagnosing serous BOT based on the analysis of morpho-ultrasound comparisons in patients after conservative and ultra-conservative operations.

Conclusion. It has been established that ultrasound diagnostics is of decisive importance both in the initial diagnosis and in the dynamic observation of patients with conservative and ultra-conservative surgery for serous BOT. Echography makes it possible to diagnose a tumor in the ovary in 83.3% of cases and to reject the diagnosis in 86.7% of cases.

Journal of Modern Oncology. 2021;23(1):106-111
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Treatment of advanced small cell lung cancer. Clinical case and literature review
Menshikov K.V., Sultanbaev A.V., Musin S.I., Menshikova I.A., Nasretdinov A.F., Sultanbaeva N.I.
Abstract

Lung cancer is one of the most common tumors in humans. The incidence is in one of the leading positions. In 2019 1327 patients with this pathology were identified in the Republic of Bashkortostan. Of these, with stage III of the disease – 28.7%, with stage IV 45.8%, which is higher. Small cell lung cancer (SCLC) is one of the most prognostically unfavorable malignant tumors in humans. About 15% of lung tumors are SCLC. The first combination for the treatment of advanced SCLC after etoposide and platinum preparations was the combination of the etoposide + carboplatin (EP) regimen with atezolizumab. In the IMpower133 study, after a median follow-up of 13.9 months. median overall survival in the atezolizumab group was 12.3 months, and in the placebo group – 10.3 months. In clinical observation, the effectiveness of the combination of the EP regimen with atezolizumab has been demonstrated. A patient with SCLC received 4 courses of EP therapy with atezolizumab and 14 injections of atezolizumab. The partial response achieved is retained. Case study efficacy and satisfactory safety profile of the combination of atezolizumab and the EP regimen.

Journal of Modern Oncology. 2021;23(1):112-115
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Comparison of the efficacy of first-line therapy with different generations of EGFR tyrosine kinase inhibitors in patients with advanced EGFR-associated non-small cell lung cancer: a network meta-analysis of overall survival data
Bogdanov A.A., Moiseenko F.V., Egorenkov V.V., Bogdanov A.A., Volkov N.M., Fedyanin M.Y.
Abstract

The lack of trials directly comparing 2nd and 3rd generation EGFR tyrosine kinase inhibitors (TKI) do not allows to determine the optimal treatment approach. The main objective of this study was to compare the survival advantage achieved with these options.

Materials and methods. As a result of a systematic search in the PubMed, ClinicalTrials.gov databases, as well as in the materials of international conferences American Society of Clinical Oncology and European Society for Medical Oncology data on the overall survival showed in 11 open randomized trials comparing different generation TKI monotherapy in TKI naïve EGFR mutated non-small-cell lung carcinoma (NSCLC), both in the general population and in subgroups including sex, age, mutational status, smoking status. Using the package netmeta for the programming language R, a network meta-analysis of the obtained data was carried out using a frequency framework.

Results. The 11 selected studies, including 3251 participants, had the following comparison groups: 6 studies (ENSURE, EURTAC, IPASS, NEJ002, OPTIMAL CTONG-0802, WJTOG3405) compared 1st generation TKIs and standard platinum-based drugs (CT); 2 studies (LUX-Lung 3, LUX-Lung 6) compared 2nd generation TKIs and CT; 2 studies (ARCHER 1050, LUX-Lung 7) compared 2nd generation TKIs and 1st generation TKIs; one study (FLAURA) compared 3rd generation TKI and the 1st generation TKIs. It was shown that for overall survival in comparison with CT, 3rd generation TKIs [hazard ratio – HR 0.84 (0.64; 1.08) and 2nd generation (HR 0.86 (0.74; 1.00)] have the same effectiveness. Subgroup analysis did not reveal significant differences in OS except for the subgroup of patients with a deletion in exon 19 of the EGFR gene, where the use of 2nd generation TKIs in comparison with CT had a statistically significant difference – HR 0.71 (0.37; 0.97).

Conclusions. The network meta-analysis of the overall survival data of clinical trials of the use of different generations TKIs as the first line treatment in patients with EGFR-associated NSCLC showed that the use of TKIs of the 3rd and 2nd generation has the same efficacy, and the TKIs of the 2nd generation increase the total survival in a group of patients carrying a mutation in exon 19 of the EGFR gene.

Journal of Modern Oncology. 2021;23(1):116-120
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Stomach cancer. Clinical significance of the expression of key components of PD-1/PD-L1 immune checkpoint
Kovaleva O.V., Podlesnaya P.A., Gratchev A.N., Chang V.L., Ognerubov N.A., Kushlinskii N.E.
Abstract

Stomach cancer is one of the most common tumors of the gastrointestinal tract. In Russia, stomach cancer is ranked fourth in incidence among malignancies and gives ground for lung, breast and colon cancers. Although the success of PD-1/PD-L1 inhibitors application in clinical practice has been proven in cases of many forms of malignancies, the advantages of application of these types of drugs in cases of stomach cancer has not yet been determined. The purpose of this review is to analyze modern studies concerning the clinical significance of PD-1 and PD-L1 expression in stomach tumors and to find the prospects of immunotherapy these tumors. The large number of studies are currently being described, concerning the analysis of the expression of PD-1, PD-L1 levels in tumor cells and soluble forms of these proteins sPD-1 and sPD-L1 in the serum in patients with stomach cancer. However, their clinical significance is unclear, and in many cases the predictive role of PD-L1 expression for the efficacy of immunotherapy is not yet clearly defined. Further accumulation of knowledge in this area can help to improve the efficacy of existing immunotherapy methods and to develop new predictive criteria.

Journal of Modern Oncology. 2021;23(1):122-127
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Differential diagnosis and treatment of rare forms of primary peritoneal tumors – solitary fibrous and desmoplastic small round cell tumors
Abdullaev A.G., Kozlov N.A., Schakhpazyan N.K., Tsigankova A.V.
Abstract

Solitary fibrous tumor and desmoplastic small round cell tumor are primary peritoneal malignant tumors. Despite their morphological differences, these diseases are united by low morbidity, the lack of pathogenic symptoms, similar radiological signs, and scant knowledge of prognostic factors. Considering the low morbidity, reliable differential diagnostic signs have not been established at present, which greatly complicates the timely formulation of the diagnosis. On the contrary, cases of choosing the wrong treatment tactics and the lack of a unified management algorithm are increasingly being identified. Radiation and instrumental diagnostic methods such as computed tomography, magnetic resonance imaging, laparoscopy are crucial in determining the extent of the tumor, it is necessary to take into account the biological characteristics of the tumor (morphological type), which affect the nature of tumor growth. With a solitary fibrous tumor and a desmoplastic small-round cell tumor, the computed tomography picture is characterized by the presence of isolated nodular formations in any part of the abdominal cavity, which can also be accompanied by a large omentum, ascites, an increase in retroperitoneal lymph nodes, and distant metastasis to the lungs and bones is possible. In general, the main task of diagnosing a primary peritoneal neoplasm is to take sufficient quality biological material, with the leading role in the diagnosis being given to histological and immunohistochemical studies. On the other hand, the independent experience of many clinics does not exceed single surveillance. This information does not allow doctors to confidently navigate the problem; accordingly, there is a need for multicenter and, possibly, prospective, randomized scientific research in order to develop a unified algorithm for managing patients with primary peritoneal tumors. The approaches to the treatment of these tumors are currently not standardized and not well studied due to the rarity of the pathology. According to the available information, the treatment of desmoplastic small round cell tumors is based on multimodal therapy, including systemic chemotherapy and surgery, and possibly radiation therapy. Traditional treatment algorithms for this pathology include the surgical stage and systemic or intracavitary chemotherapy, while the treatment sequence may be different and depends primarily on the prevalence of the disease. For solitary fibrous tumor, surgical treatment, by contrast, is the method of choice. Thus, when choosing a treatment strategy for a primary peritoneal tumor, it is first of all necessary to take into account the morphological type of the tumor and rely on known data on the benefits of a particular method. In this article, we tried to present modern information on the diagnosis and treatment of rare forms of primary peritoneal tumors.

Journal of Modern Oncology. 2021;23(1):128-132
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Assessment and correction of the geriatric status of patients with metastatic colorectal cancer during the first-line systemic therapy
Alekseeva Y.V., Semiglazova T.Y., Sharashenidze S.M., Tkachenko E.V., Kasparov B.S., Brish N.A., Teletaeva G.M., Filatova L.V., Sluzhev M.I., Semiglazov V.V., Protsenko S.A., Belyaev A.M.
Abstract

Humanity is rapidly aging, about 50% of all human malignancies develop in people over 65 years old. Cancer and antineoplastic therapy are potential pathophysiological stressors that worsen the course or intensify the development of previously compensated comorbidities and geriatric syndromes. At present, the role of assessment and correction of geriatric syndromes (CGS) for the purpose of effective first-line drug therapy in patients with metastatic CRC in the elderly and senile age, based on the use of a comprehensive geriatric assessment, has not been evaluated.

Aim. Improving the efficiency of the first-line systemic antineoplastic treatment of patients with metastatic colorectal cancer in the elderly and senile age against the background of assessment and correction of the gerontological profile.

Materials and methods. The study included data on 177 patients with metastatic colorectal cancer T1-4N1-2M1 (stage IV) who underwent first-line systemic therapy based on the FOLFOX-6 scheme at the Petrov National Medical Research Centre of Oncology from 2015 to 2021. The prospective group included 59 middle-aged and elderly patients who underwent assessment and CGS on the background of first-line systemic therapy. For analyzing the impact of assessment and CGS on the efficiency (objective response, disease control, event-free survival – EFS) and the toxicity of systemic treatment, a retrospective review of the medical histories of 118 middle-aged and elderly patients who did not undergo assessment and CGS was performed.

Results. Assessment and CGS allows to improve the results of patients with metastatic colorectal cancer, independently of age and treatment regimen: the toxicity is lower in the CGS group, neutropenia grade 3 was absent in the group with CGS, without CGS 10.7 and 14.8% for elderly and middle-aged, respectively; clinically significant response is also better in the group with CGS – 87.8%; without CGS – 69% (p<0.05); the median EFS is 9.9 [8.84–11.08] months in the group with CGS, and 7.2 [4.15–10.24] months without CGS (p=0.02).

Conclusion. In order to improve the efficiency of treatment of patients with metastatic colorectal cancer in the clinical practice of oncologists, it is advisable to conduct a comprehensive geriatric assessment and correction of geriatric syndromes.

Journal of Modern Oncology. 2021;23(1):133-140
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Sarcopenia, sarcopenic obesity, myosteatosis as factors of poor prognosis in gastrointestinal tract tumors: review
Dikova T.S., Zatsepina A.Y., Fedorinov D.S., Lyadov V.K.
Abstract

Over the past decade, there has been a noticeable increase in the number of publications devoted to the analysis of body composition in the treatment of gastrointestinal malignancies. Sarcopenia (skeletal muscle depletion), sarcopenic obesity and myosteatosis are shown to have a negative impact on the results of surgical and chemotherapeutic treatment of patients with gastrointestinal tumors. The review presents in detail data on clinical value of sarcopenia, sarcopenic obesity and myosteatosis along with methodological aspects of body composition analysis. Different cut-offs and diagnostic criteria exist between “Western” and “Eastern” patient populations which makes any comparison or meta-analysis not possible right now. The review presents data from Russian and foreign studies on the influence of body composition on postoperative outcomes and survival in patients with gastrointestinal tumors. The article also discusses the influence of body composition on dose-limiting toxicity of chemotherapy. We aimed at raising awareness of clinicians regarding the high prevalence of cancer cachexia and, precisely, sarcopenia, sarcopenic obesity and myosteatosis in patients with GI tract tumors. Deeper understanding of these syndromes is the key to developing measures for prevention as well as correcting the treatment of patients with gastrointestinal tumors.

Journal of Modern Oncology. 2021;23(1):141-147
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Detection and monitoring of minimal residual disease in acute megakaryoblastic leukemia in children
Palladina A.D., Popa A.V., Valiev T.T., Nikitaev V.G., Chernysheva O.A., Kupryshina N.A., Serebryakova I.N., Shvedova T.V., Kondratchik K.L., Tupitsyn N.N.
Abstract

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML), which is associated with poor prognosis for all patients except children with t(1;22) or Down syndrome. The frequency of complete remission in case of AMKL is comparable to the frequency of complete remission in other variants of AML, and the median survival is much lower. This determines the necessity to update criteria for assessment of the effect of treatment using flow cytometry definition of the level of minimal residual disease (MRD). Nowadays, there are no unified and standardized approaches for the measurement of MRD in case of myeloid leukemia, including AMKL, which prohibits adequate assessment of the therapy effect and in some cases – determination of the indications for allogeneic hematopoietic stem cells transplantation. The article identifies diagnostic features and describes approaches for the measurement of the level of MRD in case of AMKL.

Aim. The aim is to demonstrate the algorithms for diagnosing and measuring MRD in case of AML-M7 in children.

Materials and methods. The article analyzes the clinical and immunological profile of 10 boys and 4 girls with the initial diagnosis of AMKL between the ages of 3 months – 12 years old, 13 of them have received treatment in the FSBI «N.N. Blokhin National Medical Research Center of Oncology» and one – in the GBUZ «Morozovsky DGKB» between 1995 and 2020, The measurement of MRD was carried out in 6 patients. The measurement of MRD was carried out using both morphocytochemical method and multiparameter flow cytometry with megakaryocyte markers (CD61, CD42, CD41) in combination with other myeloid markers (CD13, CD33), CD34, CD117 and aberrant markers (mainly CD7).

Results. We showed that adequate measurement of the level of MRD had required detailed immunophenotyping during diagnosis to determine the aberration of megakaryoblasts. CD9 marker (100%), CD33 myeloid marker (69.2%), stem cell antigen CD34 (46.2%), CD13 (38.2%) in addition to megakaryocyte markers (100%) were most often expressed on blast cells in case of AMKL. The CD117 antigen was present on the blasts in 33.3% of cases. The expression of the T-cell-associated CD7 antigen (46.2%) was frequent. The measurement of MRD was carried out during the treatment (usually after an induction course) on the basis of the markers of megakaryocytic cell line (CD61, CD41, CD42a, CD42b), weak CD45 expression, as well as the immunophenotype characteristics during initial diagnosis. The level of MRD ranged from completely negative (0%; 0.006%) to evident (1.05%).

Conclusion. The detection of residual tumor megakaryoblasts in case of AML-M7 using flow cytometry is a promising method to evaluate the effect of therapy. The adequate measurement of the level of MRD requires detailed immunophenotyping during the diagnosis to determine the aberration of megakaryoblasts.

Journal of Modern Oncology. 2021;23(1):148-155
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Treatment of metastatic hepatocellular carcinoma with lenvatinib. Case report and literature review
Menshikov K.V., Sultanbaev A.V., Akhmetgareeva K.T., Lipatov D.O.
Abstract

Hepatocellular carcinoma (HCC) or liver cancer is the most common primary malignant tumor of the liver, which is characterized on the first place by a poor prognosis. HCC was diagnosed in 92 patients (62.6%) in 2019 and the period from January to April 2020 in the Republic of Bashkortostan, and among them, 68.47% had stage IV cancer. International professional guidelines suggest screening for early HCC detection. Systemic drug therapy is the treatment of choice for inoperable HCC according to professional guidelines. Inhibition of the VEGF pathway is one of the current methods of therapy for advanced HCC. Lenvatinib is a tyrosine kinase inhibitor for the treatment of advanced HCC that is not subject to local interventions. This article provides a description of a clinical case of successful treatment of a 67-year-old patient with advanced hepatocellular carcinoma. He was appointed for targeted therapy with lenvatinib for HCC that was not subject to local interventions, which led to long-term stabilization. There was a positive trend in the patient’s condition from the first weeks of therapy. The working capacity was restored. The therapy showed a satisfactory tolerability profile.

Journal of Modern Oncology. 2021;23(1):156-161
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Isolated splenic metastases from colon cancer: clinical observations
Ognerubov N.A., Antipova T.S., Ognerubova M.A.
Abstract

Isolated splenic metastases from colorectal cancer after radical surgical treatment are quite rare. This frequency of metastases is explained by the anatomical, functional and immunological characteristics of the spleen. The literature usually describes single clinical cases followed by accompanied systematic analysis and discussion. Most of the cases are asymptomatic and are accidentally diagnosed, during different types of imaging tests, including increased levels of tumor markers. The progression free survival was 3 – 144 months after surgical treatment of the primary tumor in most of the patients. By the nature of the lesion, metastases can be synchronous and metachronous, as well as solitary and multiple.

Aim. To discuss two clinical observations of isolated splenic metastases in patients after left colic flexure cancer surgical treatment.

Materials and methods. We observed 2 female patients, 68 and 70 years old, with isolated splenic metastatic after left colic flexure cancer radical surgical treatment.

Results. Both cases are considered to be metachronous and the interval of absence of disease manifestations are 21 and 10 months, respectively. The patients with stage IIB and IIC left colic flexure cancer underwent left hemicolectomy followed by adjuvant polychemotherapy using regimen with 6 cycles of FOLFOX. The histological study revealed a moderately differentiated adenocarcinoma with invasion into all layers of the wall and into the surrounding tissue. There were no lymph node metastases. In the course of dynamic observation, during the next examination with the help of ultrasound examination we revealed splenic metastasis, and confirmed this using positron emission tomography/computed tomography. The disease was without clinical picture. The time interval after the surgery before diagnosis was 21 and 10 months, respectively. Surgery was performed in the volume of splenectomy. Isolated splenic metastases in the absence of other manifestations of the disease were found intraoperatively. The histological study showed the splenic metastasis of the same type of cancer as the primary tumor. The polychemotherapy using regimen with 6 cycles of XELOX was performed during the postoperative period. Patients are alive without signs of the disease over the period of 5 and 26 months, respectively.

Conclusion. Isolated splenic metastases are extremely rare, more often when the primary tumor is located in the left side of the colon. The showed cases illustrate the need and importance of the monitoring the patients after surgical treatment for colon cancer. The use of positron emission tomography/computed tomography helps to understand the real prevalence of the tumor process, without using invasive methods. The surgery in the volume of splenectomy followed by chemotherapy are the main therapeutic options. In one clinical case, the metastases were multiple, and in the other one – was solitary metastasis. Patients are alive without signs of the disease over the period of 5 and 26 months, respectively.

Journal of Modern Oncology. 2021;23(1):162-166
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Modern approaches in the first line treatment of CD30-positive peripheral T-cell lymphomas
Poddubnaya I.V., Bariakh E.A., Voloshin S.V., Gorenkova L.G., Kaplanov K.D., Kovrigina A.M., Mikhailova N.B., Pospelova T.I., Ptushkin V.V., Tumian G.S., Falaleeva N.A., Khusainova G.N.
Abstract

Relevance. Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of aggressive lymphoproliferative malignancies that account for approximately 10% of adult non-Hodgkin’s lymphomas. Despite the variety of PTCL subtypes, CHOP-like regimens are the standard first-line therapy in most cases. At the same time, the level of complete remissions at the using these schemes is about 39%, the 2-year event-free survival rate does not exceed 45%. The possibilities of subsequent therapy of patients are very limited: the median overall survival after relapse is only 6.5 months. The most significant results were obtained only in patients with relapses of anaplastic large cell lymphoma after the use of the targeted drug brentuximab vedotin – BV (conjugate of a CD30-directed monoclonal antibody and an antitumor agent). Given the favorable safety profile of this drug, a phase 3, double-blind, randomized study (ECHELON-2) was initiated and conducted comparing the efficacy and safety of the combination of BV with CHP (cyclophosphamide, doxorubicin, prednisolone) (BV+CHP) and standard CHOP regimen in previously untreated patients with CD30-positive PTCL.

Aim. Discuss the entire spectrum of unmet medical needs in the treatment of patients with PTCL and adapt existing approaches taking into account new therapeutic options (results of the protocol ECHELON-2).

Results. The advantages of the BV+CHP regimen in the treatment of previously untreated patients with CD30-positive PTCL were recognized as convincing. Given the lack of real therapeutic options, it is recommended to register in Russia a “broad” indication for BV: “treatment of previously untreated CD30-expressing peripheral T-cell lymphomas (in combination with CHP)”. It was considered expedient to include the BV+CHP regimen in the updated Clinical Guidelines for the Treatment of Lymphoproliferative Diseases.

Journal of Modern Oncology. 2021;23(1):167-171
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New developments in the treatment of follicular lymphoma/ marginal zone lymphoma (according to the Congress of the American Society of Hematology – 2020)
Babicheva L.G.
Abstract

Relevance. Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are the most common variants of indolent non-Hodgkin lymphoma (iNHL). Despite the adequate choice of the first-line therapy, 10 – 15% of affected patients with iNHL develop refractory disease, and in most of the cases the relapse of the disease among the others patients is detected, and each subsequent remission is shorter than the previous. According to the data of the National LymphoCare Study Group, the relapses that can occur during the first 2 years (POD24) after the beginning of the first-line therapy with R-CHOP in patients with FL, as well as with MZL, have a negative impact on the prognosis: 5-year overall survival in these patients decreases from 90 to 50%. The arsenal of therapy options is actively expanding along with a deep understanding of the biological basis of the disease development. At present, the most topical problem remains the choice of the best approach for each patient – the personalization of the therapy. The review includes the data from clinical trials concerning FL and MZL treatment presented at the Congress of the American Society of Hematology in 2020. There are a large number of studies concerning new anticancer drugs in the world, such as monoclonal antibodies to different targets on the surface of B-cells, macrophages, bispecific antibodies, antibody conjugates, immunomodulators, BCR signaling pathway inhibitors (Bruton tyrosine kinase, PI3K inhibitors), immune checkpoint inhibitors and many others.

Conclusion. The development of weighting approach for the choice of therapy will give a chance to patients with FL and MZL to stay alive up to the «next era» of new effective anticancer drugs. Future strategies, according to the current studies, show the trend away from the cytotoxic chemotherapy in iNHL therapy.

Journal of Modern Oncology. 2021;23(1):172-184
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Hodgkin lymphoma. ASCO, EHA and ASH 2020 news
Demina E.A.
Abstract

The review shows the most interesting and promising studies presented at major international conferences of the American Society of Clinical Oncology, the European Hematology Association, and the American Society of Hematology in 2020. The main aim of the therapy for Hodgkin lymphoma (HL), which have been formulated over the past 20 years, is the highly effective therapy and high quality of life, and the main possibility to solve this task is positron emission tomography (PET). The studies presented at conferences this year have shown that PET-adapted therapy has become the basis of modern HL therapy. The second equally interesting direction presented at the conferences this year is the widespread use of targeted (brentuximab vedotin) therapy and immunotherapy (nivolumab, pembrolizumab) in combination with standard chemotherapy not only in patients with relapsed/refractory HL, but also as first-line therapy, including the patients of an elderly section. The combination of brentuximab vedotin and immunotherapy during all lines of HL treatment, as well as brentuximab vedotin and immunotherapy consolidation after high-dose chemotherapy and autologous stem cell transplantation are another direction to improve the efficacy of therapy in patients with HL.

Journal of Modern Oncology. 2021;23(1):185-191
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The role of positron emission tomography in different types of malignant lymphomas: the results of 2020
Sarzhevskiy V.O., Mukhortova O.V.
Abstract

The review presents the results of studies published in 2020 concerning the role of positron emission tomography (PET) in the diagnosis of different types of malignant lymphomas. The authors tried to highlight the current trends in the development of the PET method in case of Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and multiple myeloma. The topic concerning the use of PET in immunotherapy is highlighted separately. There was also an emphasis on the interpretation of quantitative imaging biomarkers used in PET. The concept of PET-adapted approach in Hodgkin lymphoma, the predictive significance of PET before high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with diffuse large B-cell lymphoma, predictive value of intermediate PET in case of follicular lymphoma, the application of methionine as PET tracer to diagnose tumor burden and to measure minimal residual disease in case of multiple myeloma, the variants of atypical tumor response to the immune checkpoint inhibitors therapy, PET in diagnosing immune-mediated adverse events are currently relevant for oncologists, hematologists, radiologists and discussed in this article. In the context of the topics the authors showed the results of PET imaging of Russian patients who had PET examination in the Bakulev National Medical Research Center for Cardiovascular Surgery.

Journal of Modern Oncology. 2021;23(1):192-200
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