Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2024; 23: 24-35
Эпидемиология, клинические особенности и прогноз рецидивов медуллобластомы разных молекулярно-генетических групп у детей и подростков
https://doi.org/10.24287/1726-1708-2024-23-3-24-35Аннотация
В классификации опухолей центральной нервной системы Всемирной организации здравоохранения 2016 г. впервые было предусмотрено разделение медуллобластомы (МБ) на молекулярно-генетические группы, принадлежность к которым определяет ответ на терапию, вероятность развития рецидива, исход заболевания и прогноз. Кроме того, прогностическое значение имеет ряд генетических факторов, таких как амплификация генов семейства MYC и мутации в гене TP53. Рецидивы заболевания имеют гетерогенный характер клинического течения, плохой прогноз и продолжают оставаться сложной терапевтической задачей. Нами выполнен ретроспективный и проспективный анализ группы из 50 пациентов детского и подросткового возраста с рецидивами МБ, референс морфологии и определение молекулярно-генетической группы которых проводились в ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России в период с января 2014 г. по декабрь 2023 г. Целью работы явилось выделение специфических различий рецидива МБ у 50 пациентов детского и подросткового возраста в зависимости от принадлежности к той или иной молекулярно-генетической группе. Исследованы анатомическая локализация рецидива, время до его развития и пострецидивная выживаемость, а также эффективность использования различных опций противорецидивной терапии. Исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева.
Список литературы
1. Louis D.N., Perry А., Reifenberger G., von Deimling A., von Deimling A., Figarella-Branger D., Cavenee W.K., et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131 (6): 803–20. DOI 10.1007/s00401-016-1545-1
2. Kool M., Korshunov A., Remke M., Jones D.T.W., Schlanstein M., Northcott P.A., et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas, Acta Neuropathol 2012; 123 (4): 473–84.
3. Ryan S.L., Schwalbe E.C., Cole M., Lu Y., Lusher M.E., Megahed H., et al. MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma. Acta Neuropathol 2012; 123 (4): 501–13.
4. Sabel M., Fleischhack G., Tippelt S., Gustafsson G., Doz F., Kortmann R., et al.; SIOP-E Brain Tumour Group. Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HITSIOP-PNET4 study. J Neurooncol 2016; 129 (3): 515–24.
5. Ramaswamy V., Remke M., Bouffet E., Faria C.C., Perreault S., Cho Y.-J., et al. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 2013; 14 (12): 1200–7.
6. Northcott P.A., Hielscher T., Dubuc A., Mack S., Shih D., Remke M., et al. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol 2011; 122 (2): 231–40.
7. Warmuth-Metz M., Blashofer S., Bueren A.O., von Hoff K., Bison B., Pohl F., et al. Recurrence in childhood medulloblastoma. J Neurooncol 2010; 103 (3): 705–11.
8. Nobre L., Zapotocky M., Khan S., Fukuoka K., Fonseca A., McKeown T., et al. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma. Cell Rep Med 2020; 1 (3): 100038. DOI: 10.1016/j.xcrm.2020.100038
9. Ramaswamy V., Remke M., Bouffet E., Baile S., Clifford S., Doz F., et al. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 2016; 131 (6): 821–31.
10. Папуша Л.И., Друй А.Е., Ясько Л.А., Супик Ж.С., Земцова Л.В., Эктова А.П. и др. Прогностическое зна чение мо леку лярногенетических и клинических характеристик медуллобластом группы SHH. Вопросы гематологии/ онкологии и иммунопатологии в педиатрии 2018; 17 (3): 43–9. DOI: 10.24287/1726-1708-2018-17-3-43-49
11. Gaab C., Adolph J.E., Tippelt S., Mikasch R., Obrecht D., Mynarek M., et al. Local and Systemic Therapy of Recurrent Medulloblastomas in Children and Adolescents: Results of the P-HIT-REZ 2005 Study. Cancers (Basel) 2022; 14 (3): 471.
12. Fleischhack G. HIT-REZ 2005 Multicenter, cooperative therapy optimization study and phase II study for the treatment of children, adolescents and young adults with therapy-resistant or recurrent primitive neuroectodermal brain tumors (medulloblastomas, supratentorial PNETs) and ependymomas. [Electronic resource] URL: https://www.gpoh.de/kinderkrebsinfo/content/health_professionals/clinical_trials/closed_trials/hit_rez_2005/index_eng.html (accessed 04.09.2024).
13. Massimino M., Gandola L., Spreafico F., Biassoni V., Luksch R., Collini P., et al. No salvage using high-dose chemotherapy plus/ minus reirradiation for relapsing previously irradiated medulloblastoma. Int J Radiat Oncol Biol Phys 2009; 73: 1358–63.
14. Dunkel I.J., Gardner S.L., Garvin J.H. Jr., Goldman S., Shi W., Finlay J.L. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro Oncol 2010; 12: 297–303.
15. Slavc I., Mayr L., Stepien N., Gojo J., Aliotti Lippolis M., Azizi A.A., et al. Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach. Cancers (Basel) 2022; 14 (20): 5128. DOI: 10.3390/cancers14205128
Pediatric Hematology/Oncology and Immunopathology. 2024; 23: 24-35
Epidemiology, clinical features and prognosis for medulloblastoma relapse depending on the molecular subgroups in children and adolescents
https://doi.org/10.24287/1726-1708-2024-23-3-24-35Abstract
The 2016 World Health Organization classification of central nervous system tumors for the first time provided the division of medulloblastoma (MB) into molecular subgroups which determine treatment response, the likelihood of relapse, the outcome of the disease and prognosis. The course of the disease and prognosis are also expected to be influenced by a number of genetic factors, such as the amplification of the MYC family genes and mutations in the TP53 gene. MB relapse has a heterogeneous clinical course, poor prognosis and continues to be a therapeutic challenge. We conducted retrospective and prospective analyses of the data from the group of 50 pediatric and adolescent patients with MB relapse. A morphology review and the determination of molecular subgroups were performed at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia) from January 2014 to December 2023. The aim of the study is to identify the specific differences in MB relapse in 50 pediatric and adolescent patients, depending on their molecular subgroup. An anatomical site of relapse, time to relapse, postrelapse survival and the effectiveness of various relapse treatment regimens were studied. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.
References
1. Louis D.N., Perry A., Reifenberger G., von Deimling A., von Deimling A., Figarella-Branger D., Cavenee W.K., et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131 (6): 803–20. DOI 10.1007/s00401-016-1545-1
2. Kool M., Korshunov A., Remke M., Jones D.T.W., Schlanstein M., Northcott P.A., et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas, Acta Neuropathol 2012; 123 (4): 473–84.
3. Ryan S.L., Schwalbe E.C., Cole M., Lu Y., Lusher M.E., Megahed H., et al. MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma. Acta Neuropathol 2012; 123 (4): 501–13.
4. Sabel M., Fleischhack G., Tippelt S., Gustafsson G., Doz F., Kortmann R., et al.; SIOP-E Brain Tumour Group. Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HITSIOP-PNET4 study. J Neurooncol 2016; 129 (3): 515–24.
5. Ramaswamy V., Remke M., Bouffet E., Faria C.C., Perreault S., Cho Y.-J., et al. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 2013; 14 (12): 1200–7.
6. Northcott P.A., Hielscher T., Dubuc A., Mack S., Shih D., Remke M., et al. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol 2011; 122 (2): 231–40.
7. Warmuth-Metz M., Blashofer S., Bueren A.O., von Hoff K., Bison B., Pohl F., et al. Recurrence in childhood medulloblastoma. J Neurooncol 2010; 103 (3): 705–11.
8. Nobre L., Zapotocky M., Khan S., Fukuoka K., Fonseca A., McKeown T., et al. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma. Cell Rep Med 2020; 1 (3): 100038. DOI: 10.1016/j.xcrm.2020.100038
9. Ramaswamy V., Remke M., Bouffet E., Baile S., Clifford S., Doz F., et al. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 2016; 131 (6): 821–31.
10. Papusha L.I., Drui A.E., Yas'ko L.A., Supik Zh.S., Zemtsova L.V., Ektova A.P. i dr. Prognosticheskoe zna chenie mo leku lyarnogeneticheskikh i klinicheskikh kharakteristik medulloblastom gruppy SHH. Voprosy gematologii/ onkologii i immunopatologii v pediatrii 2018; 17 (3): 43–9. DOI: 10.24287/1726-1708-2018-17-3-43-49
11. Gaab C., Adolph J.E., Tippelt S., Mikasch R., Obrecht D., Mynarek M., et al. Local and Systemic Therapy of Recurrent Medulloblastomas in Children and Adolescents: Results of the P-HIT-REZ 2005 Study. Cancers (Basel) 2022; 14 (3): 471.
12. Fleischhack G. HIT-REZ 2005 Multicenter, cooperative therapy optimization study and phase II study for the treatment of children, adolescents and young adults with therapy-resistant or recurrent primitive neuroectodermal brain tumors (medulloblastomas, supratentorial PNETs) and ependymomas. [Electronic resource] URL: https://www.gpoh.de/kinderkrebsinfo/content/health_professionals/clinical_trials/closed_trials/hit_rez_2005/index_eng.html (accessed 04.09.2024).
13. Massimino M., Gandola L., Spreafico F., Biassoni V., Luksch R., Collini P., et al. No salvage using high-dose chemotherapy plus/ minus reirradiation for relapsing previously irradiated medulloblastoma. Int J Radiat Oncol Biol Phys 2009; 73: 1358–63.
14. Dunkel I.J., Gardner S.L., Garvin J.H. Jr., Goldman S., Shi W., Finlay J.L. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro Oncol 2010; 12: 297–303.
15. Slavc I., Mayr L., Stepien N., Gojo J., Aliotti Lippolis M., Azizi A.A., et al. Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach. Cancers (Basel) 2022; 14 (20): 5128. DOI: 10.3390/cancers14205128
