Epidemiology, clinical features and prognosis for medulloblastoma relapse depending on the molecular subgroups in children and adolescents

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Abstract

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.

About the authors

A. E. Sysoev

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: andrey.sysoev2011@yandex.ru
ORCID iD: 0009-0005-1920-9343

Andrey E. Sysoev Deputy Head of the Department of Neurooncology, a pediatric oncologist.

1 Samory Mashela St., Moscow 117997

Russian Federation

L. I. Papusha

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7750-5216

Moscow

Russian Federation

A. I. Karachunskiy

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-9300-198X

Moscow

Russian Federation

A. V. Protsvetkina

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-8562-8945

Moscow

Russian Federation

N. B. Yudina

Voronezh Regional Children’s Clinical Hospital No 1

ORCID iD: 0000-0002-7305-6959

Voronezh

Russian Federation

L. G. Fechina

Regional Children’s Clinical Hospital No 1

ORCID iD: 0000-0002-1885-3912

Yekaterinburg

Russian Federation

G. R. Kazaryan

Nizhnevartovsk Regional Clinical Children’s Hospital

ORCID iD: 0000-0002-1881-7444

Nizhnevartovsk

Russian Federation

O. E. Nikonova

The F.P. Haass Center of Pediatric Oncology and Hematology, Regional Children’s Clinical Hospital

Perm

Russian Federation

A. A. Merishavyan

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-5310-5928

Moscow

Russian Federation

I. G. Vilesova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-6296-4305

Moscow

Russian Federation

E. А. Salnikova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-9846-2793

Moscow

Russian Federation

A. V. Nechesnyuk

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2537-6157

Moscow

Russian Federation

А. V. Artyomov

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0628-1726

Moscow

Russian Federation

A. E. Druy

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-1308-8622

Moscow

Russian Federation

G. A. Novichkova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2322-5734

Moscow

Russian Federation

References

  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. Papusha L.I., Druy A.E., Yasko L.A., Supik Z.S., Zemtsova L.Z., Ektova A.P., et al. Prognostic value of molecular, genetic and clinical characteristics of SHH group medulloblastoma. Pediatric Hematology/Oncology and Immunopathology 2018; 17 (3): 43–9. (In Russ.).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

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Copyright (c) 2025 Sysoev A.E., Papusha L.I., Karachunskiy A.I., Protsvetkina A.V., Yudina N.B., Fechina L.G., Kazaryan G.R., Nikonova O.E., Merishavyan A.A., Vilesova I.G., Salnikova E.А., Nechesnyuk A.V., Artyomov А.V., Druy A.E., Novichkova G.A.

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