nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2022-9-4-11-26nodgo-879Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESПротонная лучевая терапия у пациентов детского возраста с опухолями центральной нервной системы: особенности метода, анализ клинических данныхProton beam therapy in pediatric patients with central nervous system tumors: method features, clinical data analysishttps://orcid.org/0000-0002-5293-9568СмирноваА. Ю.SmirnovaА. Yu.

врач-детский онколог

отделение химиотерапии онкогематологических заболеваний и трансплантации костного мозга для детей

197341

ул. Аккуратова, 2

Санкт-Петербург

Pediatric Oncologist

Department of Chemotherapy for Hematologic Diseases and Bone Marrow Transplantation for Children

197341

2 Akkuratova St.

S.-Petersburg

smirnova_a_yu@almazovcentre.ruhttps://orcid.org/0000-0001-7276-9976РадулескуГ. Г.RaduleskuG. G.

врач-детский онколог

отделение химиотерапии и комбинированного лечения опухолей у детей

197758

пос. Песочный

ул. Ленинградская, 68А

Санкт-Петербург

Pediatric Oncologist

Department of Chemotherapy and Combined Treatment of Tumors in Children

197758

68А Leningradskaya St., Pesochny

S.-Petersburg

radulesky@mail.ruhttps://orcid.org/0000-0002-6998-5771ВоробьевН. А.VorobyovN. А.

к. м. н., врач-радиотерапевт, заведующий отделением, доцент

отделение протонной терапии

кафедра онкологии

197373

ул. Глухарская, 16, корп. 2

199034

Университетская наб., 7/9

Санкт-Петербург

Cand. of Sci. (Med.), Radiation Therapist, Head of the Department, AssistantProfessor

Department Proton Radiotherapy

197373

Bldg. 2, 16 Glukharskaya St.

Department of Oncology

199034

7/9 Universitetskaya Emb.

S.-Petersburg

vorobyov@ldc.ruhttps://orcid.org/0000-0003-4071-5468БезъязычнаяИ. В.BezyazychnayaI. V.

Центр персонализированной медицины

научно-исследовательская лаборатория детской нейроиммуноонкологии

лаборант-исследователь

197341

ул. Аккуратова, 2

Санкт-Петербург

Researcher

Pesonalized Medicine Centre

Laboratory of Pediatric Neuro-Immuno-Oncology

197341

2 Akkuratova St.

S.-Petersburg

bezyazychnaya.i@gmail.comhttps://orcid.org/0000-0002-1679-5173МартыноваН. И.MartynovaN. I.

врач-радиотерапевт

отделение протонной терапии

197373

ул. Глухарская, 16, корп. 2

Санкт-Петербург

Radiation Therapist

Clinic of Radiosurgery, Stereotactic Radiotherapy and General Oncology

197373

Bldg. 2, 16 Glukharskaya St.

S.-Petersburg

martynova@ldc.ruhttps://orcid.org/0000-0001-9540-1162МоргачеваД. А.MorgachevaD. A.

врач-детский онколог

отделение химиотерапии онкогематологических заболеваний и трансплантации костного мозга для детей

197341

ул. Аккуратова, 2

Санкт-Петербург

Pediatric Oncologist

Department of Chemotherapy for Hematologic Diseases and Bone Marrow Transplantation for Children

197341

2 Akkuratova St.

S.-Petersburg

morgacheva_da@almazovcentre.ruhttps://orcid.org/0000-0002-7471-7181БелогуроваМ. Б.BelogurovaM. B.

д. м. н., профессор, ведущий научный сотрудник, заведующая отделением

Институт гематологии

197341

ул. Аккуратова, 2

отделение химиотерапии и комбинированного лечения опухолей у детей

197758

пос. Песочный

ул. Ленинградская, 68А

Санкт-Петербург

Dr. of Sci. (Med.), Professor, Leading Scientific Collaborator

Institution of Hematology

197341

2 Akkuratova St.

197758

68А Leningradskaya St., Pesochny

S.-Petersburg

deton.hospital31@inbox.ruhttps://orcid.org/0000-0002-2003-0982ДиникинаЮ. В.DinikinaYu. V.

к. м. н., заведующая лабораторией, заведующая отделением

Центр персонализированной медицины

научно-исследовательская лаборатория детской нейроиммуноонкологии

отделение химиотерапии онкогематологических заболеваний и трансплантации костного мозга для детей

197341

ул. Аккуратова, 2

Санкт-Петербург

Cand. of Sci. (Med.), Head of the Laboratory and Head of the Department

Pesonalized Medicine Centre

Laboratory of Pediatric Neuro-Immuno-Oncology

Department of Chemotherapy for Hematologic Diseases and Bone Marrow Transplantation for Children

197341

2 Akkuratova St.

S.-Petersburg

dinikina_yuv@almazovcentre.ruГБУ «Национальный медицинский исследовательский центр имени В. А. Алмазова» Минздрава РоссииРоссияAlmazov National Medical Research Centre, Ministry of Health of RussiaRussian FederationГБУЗ «Санкт-Петербургский клинический научно-практический центр специализированных видов медицинской помощи (онкологический)»РоссияSaint Petersburg Clinical Scientific and Practical Center of Specialized Medical Assistance (Oncological)Russian FederationООО «Лечебно-диагностический центр Международного института биологических систем имени Сергея Березина»; ФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияDiagnostic and Treatment Center of International Institution for Biological Systems named after Sergey Berezin; Saint-Petersburg State UniversityRussian FederationООО «Лечебно-диагностический центр Международного института биологических систем имени Сергея Березина»РоссияDiagnostic and Treatment Center of International Institution for Biological Systems named after Sergey BerezinRussian FederationГБУ «Национальный медицинский исследовательский центр имени В. А. Алмазова» Минздрава России; ГБУЗ «Санкт-Петербургский клинический научно-практический центр специализированных видов медицинской помощи (онкологический)»РоссияAlmazov National Medical Research Centre, Ministry of Health of Russia; Saint Petersburg Clinical Scientific and Practical Center of Specialized Medical Assistance (Oncological)Russian Federation202201022023941126Copyright © Смирнова А.Ю., Радулеску Г.Г., Воробьев Н.А., Безъязычная И.В., Мартынова Н.И., Моргачева Д.А., Белогурова М.Б., Диникина Ю.В., 20232023Смирнова А.Ю., Радулеску Г.Г., Воробьев Н.А., Безъязычная И.В., Мартынова Н.И., Моргачева Д.А., Белогурова М.Б., Диникина Ю.В.Smirnova А.Y., Radulesku G.G., Vorobyov N.А., Bezyazychnaya I.V., Martynova N.I., Morgacheva D.A., Belogurova M.B., Dinikina Y.V.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/879

   Актуальность. Опухоли центральной нервной системы (ЦНС) являются наиболее часто встречающимися солидными опухолями детского возраста, подход к лечению которых является мультимодальным и сочетает хирургический этап, интенсивную полихимиотерапию (ПХТ) и  лучевую терапию (ЛТ). Вследствие токсичности, преимущественно отдаленной, ЛТ имеет ограниченное применение у пациентов детского возраста, особенно для детей младше 3 лет. Физические особенности протонной ЛТ (ПЛТ) позволяют минимизировать риск и виды токсических осложнений в сравнении с фотонной ЛТ (ФЛТ) и делают ее предпочтительнее в детском возрасте.   Цель исследования – проанализировать опыт проведения ПЛТ у пациентов младше 18 лет с различными вариантами злокачественных новообразований (ЗНО) ЦНС с оценкой факторов риска острой и отдаленной токсичности и ее клинических проявлений.   Материалы и методы. Проведен ретроспективный анализ 63 курсов ПЛТ, выполненной 58 пациентам со ЗНО ЦНС за период с 2018 по 2022 гг. на базе Центра протонной терапии ОО «ЛДЦ МИБС». Наиболее детально оценивались проявления локальной и системной острой токсичности с оценкой влияния возраста, объема ЛТ, использования предшествующей химиотерапии (ХТ) и сочетанной химиолучевой терапии на степень выраженности нежелательных явлений (НЯ).   Результаты. В исследуемой когорте преобладали пациенты с эмбриональными ЗНО ЦНС (72,3 %). Медиана возраста составила 5 лет 2 месяца, медиана периода наблюдения – 15 мес. В 36 % случаев был достигнут полный ответ к началу проведения ПЛТ. Преобладали пациенты с проведением краниоспинального облучения (КСО) (60 %) в сочетании с локальной ПЛТ. Среди проявлений острой токсичности преобладали НЯ I–II степени. Наиболее часто встречались местные реакции в виде дерматитов (84 %), фокальных алопеций (96 %). Среди системных НЯ чаще всего имели место гематологические осложнения (84 %). Более выраженный профиль токсичности зарегистрирован в группе пациентов с КСО, в то время как потенцирующая ХТ, возраст пациента, предшествующая ПХТ не оказывали значимого влияния на выраженность большинства оцениваемых НЯ (p > 0,05). Оценка поздних токсических эффектов (ПТО) была затруднительна ввиду недлительного периода катамнеза, кумулятивного влияния других методов лечения на развитие НЯ. Среди зарегистрированных ПТО: фокальные алопеции (14 %), эндокринопатии (7 %), неврологические проявления (6 %). У 1 (2 %) ребенка зарегистрированы тяжелый неврологический дефицит, вторичная эпилепсия с регрессом психомоторных навыков, что также может быть ассоциировано с потенцирующим влиянием предшествующей ХТ и высокодозной ХТ.   Заключение. Проведенный анализ наших данных и обзор литературы позволяют сделать заключение об относительно низком профиле токсичности ПЛТ, что является определяющим критерием для использования у пациентов детского возраста. Основным фактором риска развития НЯ является КСО. Приемлемая острая токсичность повторной ПЛТ позволяет использовать данный метод лечения у пациентов с прогрессированием / рецидивом заболевания при отсутствии альтернативных терапевтических опций.

   Introduction. Central nervous system (CNS) tumors are the most common pediatric solid tumor, that need multimodality treatment approach including surgery, intensive chemotherapy (CT) and radiotherapy (RT). Due to toxicity, mostly late, RT has limited use in children, especially those under 3 years of age. The physical characteristics of proton beam therapy (PBT) minimize the risk and types of toxicity compared to photons, making it the preferred choice for pediatric use.   Aim – to analyze the experience of PBT in patients under 18 years of age with various types of CNS malignancies, the assessment of risk factors for acute and late toxicity and its clinical manifestations. Materials and methods. A retrospective analysis of 63 courses of PBT performed in 58 patients with CNS malignancies for the period from 2018 to 2022 was carried out on Proton Center of the Sergey Beresin Medical Institute. The manifestations of local and systemic toxicity (predominantly acute) were analyzed, with an assessment of the influence of age, the volume of RT, the use of previous and concomitant CT on the severity of adverse events (AE).   Results. In the study cohort, patients with embryonal CNS malignancies predominated (72.3 %). Median age was 5 years 2 months, median follow-up was 15 months. In 36 % of cases, a complete response was achieved by the start of PBT. Patients with craniospinal irradiation (CSI) prevailed (60 %). Among the manifestations of toxicity, AE grade I–II predominated. The most common AE were local reactions (dermatitis (84 %), focal alopecia (96 %)). Among systemic AE, hematological complications (84 %) were the most often occurred. A more pronounced toxicity profile was registered in the group with CSI, while concomitant CT, the patient’s age, previous CT did not significantly affect the severity of most of the assessed AE parameters (p > 0.05). The analysis of late toxic effects was difficult due to the short follow-up period, the cumulative effect of other treatment modalities on the AE’s development. The reported complications included persistent focal alopecia (14 % of cases), endocrinopathies (7 %), neurological manifestations (6 %). One (2 %) child had a severe neurological deficit, secondary epilepsy with psychomotor regression, which can also be associated with the potentiating effect of previous CT and high-dose CT.   Conclusion. The analysis of our data and literature review allows to conclude that PBT has relatively low toxicity profile, which is the determining factor for choosing this method of RT in pediatric patients. The main risk factor of AE’s was CSI. The acceptable acute toxicity of repeat PBT makes it possible to be used in pts with disease progression or relapse in case of absence of alternative therapeutic options.

детиопухоли ЦНСлучевая терапияпротонное облучениетоксичностьchildrenCNS tumorsradiotherapyproton beam radiationtoxicityРабота выполнена при финансовой поддержке Министерства науки и высшего образования Российской Федерации (соглашение № 075-15-2022-301 от 20. 04. 2022)This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2022-301)ReferencesSmoll N. R., Drummond K. J. The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neuroscience. 2012; 19 (11): 1541–4. doi: 10.1016/j.jocn.2012.04.009.Smoll N. R., Drummond K. J. The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neuroscience. 2012; 19 (11): 1541–4. doi: 10.1016/j.jocn.2012.04.009.Blaney S. M., Adamson P. C., Helman L. J. Pizzo & Poplack’s Pediatric Oncology. 8 <sup>th</sup> edition. Wolters Kluwer Health, 2020. Pp. 394–5.Blaney S. M., Adamson P. 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The authors declare that there are no conflicts of interest present.