nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2021-8-3-30-42nodgo-741Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESЛечение рецидивов саркомы Юинга у детей и подростков: современный взглядTreatment of Ewingʼs sarcoma in children and adolescents: new visionhttps://orcid.org/0000-0002-2310-0106РоманцоваО. М.RomantsovaO. M.

Ольга Михайловна Романцова,  врач-детский онколог детского онкологического отделения хирургических методов лечения с проведением химиотерапии № 3 (опухолей опорно-двигательного аппарата)

SPIN-код: 4629-6784   

115478 Москва, Каширское шоссе, 23

Pediatric Oncologist of Pediatric Oncology Department of Surgical Methods of Treatment with Chemotherapy No. 3 (Tumors of the Musculoskeletal System) of Research Institute of Pediatric Oncology and Hematology

SPIN-code: 4629-6784 

23 Kashirskoe Shosse, Moscow, 115478

dr.roma1986@gmail.comhttps://orcid.org/0000-0002-2839-5222НисиченкоД. В.NisichenkoD. V.

к.м.н., старший научный сотрудник детского онкологического отделения хирургических методов лечения с проведением химиотерапии № 3 (опухолей опорно-двигательного аппарата)

SPIN-код: 2597-1880 

115478 Москва, Каширское шоссе, 23

Cand. of Sci. (Med.), Senior Researcher of Pediatric Oncology Department of Surgical Methods of Treatment with Chemotherapy No. 3 (Tumors of the Musculoskeletal System) of Research Institute of Pediatric Oncology and Hematology

SPIN-code: 2597-1880 

23 Kashirskoe Shosse, Moscow, 115478

nisichenko@gmail.comhttps://orcid.org/0000-0002-8149-254XХестановД. Б.KhestanovD. B.

к.м.н., старший научный сотрудник детского онкологического отделения хирургических методов лечения с проведением химиотерапии № 3 (опухолей опорно-двигательного аппарата)

SPIN-код: 9756-1732 

115478 Москва, Каширское шоссе, 23

Cand. of Sci. (Med.), Senior Researcher of Pediatric Oncology Department of Surgical Methods of Treatment with Chemotherapy No. 3 (Tumors of the Musculoskeletal System) of Research Institute of Pediatric Oncology and Hematology

SPIN-code: 9756-1732 

23 Kashirskoe Shosse, Moscow, 115478

hestanov@mail.ruhttps://orcid.org/0000-0003-0883-7801ХайрулловаВ. В.KhairullovaV. V.

врач-детский онколог детского онкологического отделения хирургических методов лечения с проведением химиотерапии № 3 (опухолей опорно-двигательного аппарата)

115478 Москва, Каширское шоссе, 23

Pediatric Oncologist of Pediatric Oncology Department of Surgical Methods of Treatment with Chemotherapy No. 3 (Tumors of the Musculoskeletal System) of Research Institute of Pediatric Oncology and Hematology 

23 Kashirskoe Shosse, Moscow, 115478

vini999_999@mail.ruhttps://orcid.org/0000-0002-2839-5222ДзампаевА. З.DzampaevA. Z.

к.м.н., заведующий детским онкологическим отделением хирургических методов лечения с проведением химиотерапии № 3 (опухолей опорно-двигательного аппарата) НИИ детской онкологии и гематологии 

115478 Москва, Каширское шоссе, 23

Cand. of Sci. (Med.), Head of Pediatric Oncology Department of Surgical Methods of Treatment with Chemotherapy No. 3 (Tumors of the Musculoskeletal System) of Research Institute of Pediatric Oncology and Hematology 

23 Kashirskoe Shosse, Moscow, 115478

dzampaev@list.ruhttps://orcid.org/0000-0002-2945-284XКиргизовК. И.KirgizovK. I.

к.м.н., заместитель директора по научной и образовательной работе НИИ детской онкологии и гематологии

SPIN-код: 3803-6370 

115478 Москва, Каширское шоссе, 23

Cand. of Sci. (Med.), Deputy Director for Scientific and Educational Work of Research Institute of Pediatric Oncology and Hematology 

23 Kashirskoe Shosse, Moscow, 115478

k.kirgizov@ronc.ruФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of RussiaRussian Federation202117102021833042Copyright © Романцова О.М., Нисиченко Д.В., Хестанов Д.Б., Хайруллова В.В., Дзампаев А.З., Киргизов К.И., 20212021Романцова О.М., Нисиченко Д.В., Хестанов Д.Б., Хайруллова В.В., Дзампаев А.З., Киргизов К.И.Romantsova O.M., Nisichenko D.V., Khestanov D.B., Khairullova V.V., Dzampaev A.Z., Kirgizov K.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/741

Введение. За последние десятилетия удалось достичь существенно большего понимания в морфологии и молекулярно-биологических особенностях опухолей семейства саркомы Юинга (ОССЮ). Более 70 % рецидивов происходят в течение 2 лет от момента постановки диагноза. Примерно в 2/3 случаев рецидив возникает в отдаленных местах, этот тип рецидивирования особенно часто встречается у пациентов, изначально имеющих метастазы. Напротив, изолированный местный рецидив наиболее часто (в 1/5 случаев) возникает у пациентов с локализованной формой заболевания. У половины пациентов рецидив заболевания был выявлен при плановом обследовании, протекал бессимптомно и был случайной находкой.Цель исследования – оценить эффективность противорецидивного лечения у больных с ОССЮ, выработать алгоритм персонифицированного подхода, улучшить результаты общей и безрецидивной выживаемости у детей и подростков с ОССЮ.Материалы и методы. В наше исследование вошли пациенты с подтвержденным диагнозом саркомы Юинга (СЮ), получавшие лечение с 2008 по 2019 г. Анализ катамнестических данных закрыт 19.02.2021. В исследование вошли 274 пациента в возрасте от 6 месяцев до 18 лет, средний возраст составил 11,6 года. Два ребенка на момент исследования были младше 1 года. Двенадцать (4,3 %) пациентов вышли из-под наблюдения в срок от 2 до 9 мес после начала лечения, в последующий анализ мы их не включали. Прослежены и проанализированы 262 больных с диагнозом СЮ, получившие лечение по протоколам в НИИ детской онкологии и гематологии ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России. У 48 (18,3 %) пациентов из 262 выявлен рецидив заболевания – группа исследования; у 58 (22,1 %) – прогрессирование заболевания на фоне программного лечения. В 70,8 % (34/48) случаев был выявлен изолированный рецидив, в 14 (29,2 %) – комбинированный. Поражение только легочной ткани при рецидиве заболевания встречалось в 19/48 (39,6 %) случаях, местный рецидив без метастазирования – в 7/48 (14,5 %) наблюдениях. В целом метастатическое поражение легких встречалось в 66,6 % случаев. Поражение головного мозга и лимфатических узлов встречалось в 4 % наблюдений. Больше всего больных было в возрастной группе с 11 до 17 лет включительно – 38/48 пациентов, что составило 79 %. Все 48 больных из группы исследования получали противорецидивную терапию в зависимости от срока развития рецидива заболевания. При поздних рецидивах использовалась схема первичного лечения: альтернирующие курсы химиотерапии (ХТ) препаратами винкристин/доксорубицин/циклофосфамид и этопозид/ифосфамид. При ранних рецидивах наиболее часто использовались 2 схемы: винкристин/топотекан/циклофосфамид и винкристин/иринотекан/темозоломид (VIT). Частота положительного ответа при использовании противорецидивной схемы лечения VIT составила 60 %, а время до прогрессирования – 7,6 мес. При использовании схемы с топотеканом частота ответа составила 45 %, а время до прогрессирования – 7 мес.Результаты. Общая выживаемость (ОВ) пациентов при выявлении рецидива была достоверно (p £ 0,05) выше по сравнению с группой больных, у которых возникло прогрессирование заболевания, что связано с эффектом противорецидивной ХТ. При анализе ОВ пациентов с СЮ следует отметить, что 5-летняя выживаемость всех пациентов (n = 262) составила 66,3 ± 3,3 % по сравнению с группой больных с подтвержденным рецидивом (n = 48) – 53 ± 8,1 %. Медиана в группе пациентов с рецидивом составила 39,3 мес. Время наблюдения в группе с рецидивом СЮ (n = 48) составило в среднем 52,2 ± 32,3 мес (от 12,6 до 142 мес). Также была проанализирована ОВ больных в зависимости от интервала рецидива заболевания. За интервал № 1 мы приняли срок от начала основного лечения до выявления 1-го рецидива, медиана составила 37,2 мес. Интервал № 2 – от даты выявления 1-го рецидива заболевания до выявления 2-го рецидива. При времени наблюдения 58,8 ± 29,1 мес (от 28,6 до 108 мес) медиана не была достигнута. Второй рецидив возникал достоверно реже по сравнению с первым рецидивом (р = 0,000001).Заключение. Исход для пациентов с рецидивами СЮ остается неблагоприятным, а стандартный подход к их лечению еще не установлен. Стандартная ХТ 1-й и 2-й линий может быть эффективной у большинства больных с точки зрения уменьшения симптомов и увеличения времени до дальнейшего прогрессирования, но полная ремиссия остается труднодостижимой. Требуется дальнейшее мультидисциплинарное изучение факторов прогноза, эффектов различных схем и протоколов противорецидивного лечения, а также включение в программу терапии высокодозной ХТ с аутологичной трансплантацией.

Introduction. Over the past decades, a significantly greater understanding of the morphology and molecular biological characteristics of tumors of the Ewing sarcoma family (ESFT) has been achieved. More than 70 % of relapses occur within 2 years from the date of diagnosis. In about 2/3 of cases, relapse occurs in distant places; this type of relapse is especially common in patients who initially have metastases. On the contrary, isolated local metastasis most often (in 1/5 of cases) occurs in patients with a localized form of the disease. In half of the patients, a relapse of the disease was detected during a routine examination, was asymptomatic and was a chance find.Purpose of the study – to evaluate the effectiveness of anti-relapse treatment in patients with ESFT, to develop an algorithm for a personalized approach, to improve the results of overall and relapse-free survival in children and adolescents with ESFT.Materials and methods. Our study included patients with a confirmed diagnosis of Ewing sarcoma (ES), who received treatment from 2008 to 2019. The analysis of follow-up data was closed on 19.02.2021. The study included 274 patients aged 6 months to 18 years, the average age was 11.6 years. Up to 1 year in our study there were 2 children. Twelve (4.3 %) patients went out of follow-up within 2 to 9 months from the start of treatment; we did not include them in the subsequent analysis. Analyzed were 262 patients with ES who received treatment according to the protocols at the Research Institute of Pediatric Oncology and Hematology of the N.N. Blokhin National Medical Research Center of Oncology. A relapse of the disease was revealed in 48 (18.3 %) children out of 262 – the study group; 58 (22.1 %) patients showed disease progression during treatment. In 70.8 % (34/48) patients had an isolated relapse, in 14 (29.2 %) cases – a combined one. The defeat of only the lung tissue with a relapse of the disease occurred in 19/48 (39.6 %) cases, local relapse without metastasis – 7/48 (14.5 %) cases. In general metastatic lung disease occurred in 66.6 % of cases. The defeat of the brain and lymph nodes occurred in 4 %. Most of the patients were in the group from 11 to 17 years, inclusive – 38/48 patients, which amounted to 79 %. All 48 patients from the study group received anti-relapse therapy depending on the duration of the disease relapse. For late relapses the primary treatment regimen was used: alternating courses of chemotherapy with vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. In early relapses two regimens were most used: vincristine/topotecan/cyclophosphamide and vincristine/irinotecan/temozolomide (VIT). The positive response rate with the antirelapse VIT regimen was 60 %, and the time to progression was 7.6 months. With the topotecan regimen the response rate was 45 % and the time to progression – 7 months.Results. The overall survival (OS) rate of patients when a relapse was detected was significantly (p £ 0.05) higher when compared with the group of patients who had progression of the disease, which is associated with the effect of anti-relapse chemotherapy. When analyzing OS of patients with ES it should be noted that the 5-year survival rate of all patients (n = 262) was 66.3 ± 3.3 %, compared with the group of patients with confirmed relapse (n = 48) – 53 ± 8.1 %. The median in the group of patients with relapse was 39.3 months. The follow-up time in the group with recurrent ES disease averaged 52.2 ± 32.3 months (from 12.6 to 142 months). OS of patients was analyzed depending on the interval of disease recurrence. The Interval No. 1 was from the beginning of the main treatment to the first relapse, with a median of 37.2 months. Interval No. 2 – from the date of the first relapse to the date of the second relapse with a follow-up time of 58.8 ± 29.1 months (from 28.6 to 108 months), the median was not reached. The second relapse occurred significantly less frequently than the first relapse (p = 0.000001).Conclusion. The outcome for patients with recurrent ES remains poor, and a standard approach to their treatment has not yet been established. Standard first and second lines chemotherapy can be effective in most patients in terms of reducing symptoms and increasing the time to further progression, but complete remission remains hard to reach. Further multidisciplinary study of prognostic factors, effects of various treatment regimens and protocols, study of the inclusion of targeted drugs in the therapy program is required.

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The authors declare that there are no conflicts of interest present.