Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children62710.24287/1726-1708-2022-21-2-141-156LITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫThe impact of response to induction chemotherapy on the event-free and overall survival in patients with high-risk neuroblastoma: a systematic review and meta-analysisОценка влияния ответа на индукционный этап терапии у пациентов с нейробластомой группы высокого риска на бессобытийную и общую выживаемость: систематический обзор и метаанализhttps://orcid.org/0000-0002-3767-4477ShamanskayaT. V.ШаманскаяТ. В.
Russian Federation

Tatyana V. Shamanskaya, Cand. Med. Sci., Head of the Department for Embryonal Tumor Research at the Institute of Oncology, Radiology and Nuclear Medicine

1 Samory Mashela St., Moscow 117997

Шаманская Татьяна Викторовна, канд. мед. наук, заведующая отделом изучения эмбриональных опухолей Института онкологии, радиологии и ядерной медицины

117997, Москва, ул. Саморы Машела, 1

shamanskaya.tatyana@gmail.comhttps://orcid.org/0000-0002-3704-8783KachanovD. Yu.КачановД. Ю.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-3792-1682YadgarovM. Ya.ЯдгаровМ. Я.
Russian Federation

Moscow

Москва

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России080720222121411562506202225062022Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/627

   Neuroblastoma (NB) is one of the most common embryonal tumors of childhood. About 40 % of all NB patients are stratified into the high-risk group and require multimodal therapy. The goal of induction treatment is a maximum reduction of the primary tumor and metastases. Response to induction therapy is an important prognostic factor affecting long-term survival. The protocol of our meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO): ID-CRD42022311162. The PubMed, Google Scholar and Cochrane Library databases were searched for relevant studies published over the last 15 years (2007–2022). A total of 12 studies were selected for analysis where response to induction therapy was assessed in patients with high-risk NB in accordance with the International NB Response Criteria, and an analysis of the impact of response on overall (OS) and event-free (EFS) survival was carried out. The meta-analysis included 3431 patients: a good response to induction therapy (complete response / very good partial response) was achieved in 1702 patients, a poor response (partial response / mixed response / stable disease) – in 1729 patients. The patients with a good response had a 28 % lower relative risk (RR) of relapse / progression within 5 years of diagnosis compared with the patients with a poor response: RR = 0.72 (0.64 to 0.80), p-value for effect < 0.001, p-value for heterogeneity < 0.001, I2 = 65 %. The relative risk of death within 5 years of diagnosis was 31 % lower in the patients with a good response: RR = 0.69 (0.57 to 0.83), p-value for effect < 0.001, p-value for heterogeneity < 0.001, I2 = 78 %. A separate analysis of results of international cooperative groups (GPOH, COG and SIOPEN) also revealed a statistically significant relationship between partial response / mixed response / stable disease response to induction therapy and EFS (p < 0.001). The highest level of evidence was obtained for separate subgroups – GPOH (a moderate level of evidence for EFS) and SIOPEN (a moderate level of evidence for EFS and OS) – due to low clinical inconsistency (standardized response criteria and therapy) as well as low statistical inconsistency. The study had certain limitations that are described in detail in the article. Response to induction chemotherapy is an important factor that affects EFS and OS in patients with high-risk NB.

   Нейробластома (НБ) является одной из самых частых эмбриональных опухолей детского возраста. Около 40 % всех пациентов стратифицируются в группу высокого риска и требуют проведения мультимодальной терапии. Цель индукционного этапа лечения – максимальное сокращение первичной опухоли и метастазов. Ответ на индукцию является важным прогностическим фактором, влияющим на отдаленную выживаемость. Протокол метаанализа зарегистрирован в Международном проспективном реестре систематических обзоров (PROSPERO): ID-CRD42022311162. Проведен поиск исследований, опубликованных за последние 15 лет (2007–2022 гг.) в базах PubMed, Google Scholar, Cochrane Library. Всего для анализа было выбрано 12 работ, в которых проведена оценка ответа на индукционный этап терапии в группе больных высокого риска в соответствии с критериями Международной системы оценки ответа у пациентов с НБ и выполнен анализ влияния ответа на общую (ОВ) и бессобытийную (БСВ) выживаемость. В метаанализ был включен 3431 пациент: хороший ответ на индукционный этап терапии (полный ответ / очень хороший частичный ответ) был достигнут у 1702 пациентов, плохой ответ (частичный ответ / смешанный ответ / стабилизация) – у 1729 больных. Пациенты с хорошим ответом имели на 28 % меньший относительный риск (ОР) рецидива/прогрессирования в течение 5 лет от момента постановки диагноза в сравнении с больными с плохим ответом: ОР = 0,72 (от 0,64 до 0,80), р-значение для эффекта < 0,001, р-значение для неоднородности < 0,001, I2 = 65%. Риск летального исхода в течение 5 лет от постановки диагноза был на 31 % ниже у пациентов с хорошим ответом: ОР = 0,69 (от 0,57 до 0,83); p-значение для эффекта < 0,001, p-значение для неоднородности < 0,001, I2 = 78 %. При разделении результатов по отдельным международным кооперированным группам (GPOH, COG и SIOPEN) также была выявлена статистически значимая связь ответа на индукционный этап терапии с БСВ (p < 0,001). Наиболее высокий уровень доказательств получен при рассмотрении отдельных подгрупп – GPOH (средний уровень доказательств применительно к БСВ) и SIOPEN (средний уровень доказательств для БСВ и ОВ), что было связано с наличием относительно однородных подгрупп пациентов со стандартизованной оценкой ответа и терапией, а также с низкой статистической несогласованностью. Исследование имело определенные ограничения, которые подробно указаны в статье. Ответ на индукционную терапию является важным фактором, влияющим на БСВ и ОВ при лечении пациентов с НБ группы высокого риска.

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