Preview

MD-Onco

Advanced search

Diagnosis and treatment of pediatric brain tumors

https://doi.org/10.17650/2782-3202-2025-5-1-47-58

Abstract

Brain tumors are the most common solid tumors in children and are associated with high mortality. The most common childhood brain tumors are grouped as low­grade gliomas, high grade gliomas, ependymomas, and embryonal tumors, according to the World Health Organization (WHO). Advances in molecular genetics have led to a shift from pure histopathological diagnosis to integrated diagnosis. For the first time, these new criteria were included in the WHO classification published in 2016 and has been further updated in the 2021 edition. Integrated diagnosis is based on molecular genomic similarities of the tumor subclasses, and it can better explain the differences in clinical courses of previously histopathologically identical entities. Important advances have also been made in pediatric neuro­oncology. A growing understanding of the molecular­genetic background of tumorigenesis has improved the diagnostic accuracy. Re­stratification of treatment protocols and the development of targeted therapies will significantly affect overall survival and quality of life. For some pediatric tumors, these advances have significantly improved therapeutic management and prognosis in certain tumor subgroups. Some therapeutic approaches also have serious long­term consequences. Therefore, optimized treatments are greatly needed.

About the Authors

E. O. Shebanova
Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation

Ekaterina Olegovna Shebanova 

Bld. 2, 8 Trubetskaya St., Moscow 119991



A. O. Kurmanova
Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991



N. V. Sevyan
Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991



E. V. Prozorenko
Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991



V. Yu. Kirsanov
Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991



References

1. Udaka Y.T., Packer R.J. Pediatric brain tumors. Neurol Clin 2018;36(3):533–56. DOI: 10.1016/j.ncl.2018.04.009

2. WHO Classification of Tumours Editorial Board. Central nervous system tumours. 5th edn. Lyon, France: IARC, 2021.

3. Li Q., Dai Z., Cao Y., Wang L. Comparing children and adults with medulloblastoma: a SEER based analysis. Oncotarget 2018;9(53):30189–98. DOI: 10.18632/oncotarget.23773

4. Miller K.D., Ostrom Q.T., Kruchko C. et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin 2021;71(5):381–406. DOI: 10.3322/caac.21693

5. Louis D.N., Perry A., Reifenberger G. 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

6. Louis D.N., Perry A., Wesseling P. et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol 2021;23(8):1231–51. DOI: 10.1093/neuonc/noab106

7. Tyurina E.V., Valiev T.T., Kumirova E.V. et al. Atypical teratoid/ rhabdoid tumors of central nervous system in children. Literature review. Voprosy onkologii = Problems in Oncology 2024;70(4):622–32. (In Russ.). DOI: 10.37469/0507-3758-2024-70-4-622-632

8. Levashov A.S., Zagidullina S.R., Valiev T.T. et al. International experience by using of the SJMB protocols in treatment of children with medulloblastoma in the age group over 3 years (literature review). Sovremennaya oncologiya = Journal of Modern Oncology 2023;25(3):385–90. (In Russ.). DOI: 10.26442/18151434.2023.3.202437

9. Pollack I.F., Agnihotri S., Broniscer A. Childhood brain tumors: current management, biological insights, and future directions. J Neurosurg Pediatr 2019;23(3):261–73. DOI: 10.3171/2018.10.PEDS18377

10. Chu T.P., Shah A., Walker D., Coleman M.P. Pattern of symptoms and signs of primary intracranial tumours in children and young adults: a record linkage study. Arch Dis Child 2015;100(12):1115– 22. DOI: 10.1136/archdischild-2014-307578

11. Reulecke B.C., Erker C.G., Fiedler B.J. et al. Brain tumors in children: initial symptoms and their influence on the time span between symptom onset and diagnosis. J Child Neurol 2008;23(2):178–83. DOI: 10.1177/0883073807308692

12. Rao P. Role of MRI in paediatric neurooncology. Eur J Radiol 2008;68(2):259–70. DOI: 10.1016/j.ejrad.2008.06.033

13. Jaju A., Li Y., Dahmoush H. et al. Imaging of pediatric brain tumors: a COG diagnostic imaging committee/SPR oncology committee/ASPNR white paper. Pediatr Blood Cancer 2023;70(Suppl 4):e30147. DOI: 10.1002/pbc.30147

14. Ellingson B.M., Bendszus M., Boxerman J. et al. Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. Neuro Oncol 2015;17(9):1188–98. DOI: 10.1093/neuonc/nov095

15. Rowe S.K., Rodriguez D., Cohen E. et al. Switching from linear to macrocyclic gadolinium-based contrast agents halts the relative T1-weighted signal increase in deep gray matter of children with brain tumors: a retrospective study. J Magn Reson Imaging 2020;51(1):288–95. DOI: 10.1002/jmri.26831

16. Cooney T.M., Cohen K.J., Guimaraes C.V. et al. Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro Oncology (RAPNO) working group. Lancet Oncol 2020;21(6):e330–e6. DOI: 10.1016/s1470-2045(20)30166-2

17. Guo B.J., Yang Z.L., Zhang L.J. Gadolinium deposition in brain: current scientific evidence and future perspectives. Front Mol Neurosci 2018;11:335. DOI: 10.3389/fnmol.2018.00335

18. Warren K.E., Vezina G., Poussaint T.Y. et al. Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro Oncology committee. Neuro Oncol 2018;20(1):13–23. DOI: 10.1093/neuonc/nox087

19. Singhi S.C., Tiwari L. Management of intracranial hypertension. Indian J Pediatr 2009;76(5):519–29. DOI: 10.1007/s12098-009-0137-7

20. McClain C.D., Soriano S.G. Anesthesia for intracranial surgery in infants and children. Curr Opin Anaesthesiol 2014;27(5):465–9. DOI: 10.1097/ACO.0000000000000112

21. Silva A.H.D., Aquilina K. Surgical approaches in pediatric neurooncology. Cancer Metastasis Rev 2019;38(4):723–47. DOI: 10.1007/s10555-019-09832-2

22. Karakhan V.B., Prozorenko E.V., Mentkevich G.L. et al. Atypical teratoid rhabdoid tumor with intratumoral advancement: significance of active surgical approach in long-term disease (109 months) with metastatic cascade. Opuholi Golovy i Sei 2022;3(12):127–35. DOI: 10.17650/2222-1468-2022-12-3-127-135

23. Rudà R., Reifenberger G., Frappaz D. et al. EANO guidelines for the diagnosis and treatment of ependymal tumors. Neuro Oncol 2018;20(4):445–56. DOI: 10.1093/neuonc/nox166

24. Roujeau T., Machado G., Garnett M.R. et al. Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg 2007;107(1 Suppl): 1–4. DOI: 10.3171/PED-07/07/001

25. Fangusaro J., Bandopadhayay P. Advances in the classification and treatment of pediatric brain tumors. Curr Opin Pediatr 2021;33(1):26–32. DOI: 10.1097/MOP.0000000000000975

26. Ludmir E.B., Grosshans D.R., Woodhouse K.D. Radiotherapy advances in pediatric neuro-oncology. Bioengineering 2018;5(4):97. DOI: 10.3390/bioengineering5040097

27. Wang T., Manohar N., Lei Y. et al. MRI-based treatment planning for brain stereotactic radiosurgery: dosimetric validationof a learning-based pseudo-CT generation method. Med Dosim 2019;44(3):199–204. DOI: 10.1016/j.meddos.2018.06.008

28. Mochizuki A.Y., Frost I.M., Mastrodimos M.B. et al. Precision medicine in pediatric neurooncology: a review. ACS Chem Neurosci 2018;9(1):11–28. DOI: 10.1021/acschemneuro.7b00388

29. The Royal College of Radiologists, Clinical Oncology. Radiotherapy dose fractionation. 3rd edn. London, UK: The Royal College of Radiologists, 2019. Pp. 70–74.

30. Park J., Yea J.W., Park J.W. Hypofractionated radiotherapy versus conventional radiotherapy for diffuse intrinsic pontine glioma: a systematic review and meta-analysis. Medicine (Baltimore) 2020;99(42):e22721. DOI: 10.1097/MD.0000000000022721

31. Levin W.P., Kooy H., Loeffler J.S., DeLaney T.F. Proton beam therapy. Br J Cancer 2005;93(8):849–54. DOI: 10.1038/sj.bjc.6602754

32. Pearl M.S., Gupta N., Hetts S.W. Interventional neuro-oncology. Handb Clin Neurol 2021;176:361–78. DOI: 10.1016/b978-0-444-64034-5.00002-x

33. Prozorenko E.V., Karakhan V.B., Bliznyukov O.P., Sevyan N.V. Recurrent petrosal tumor: meningioma or solitary fibrous tumor? Arkhiv Patologii = Russian Journal of Archive of Pathology 2023;85(2):27–31. (In Russ.). DOI: 10.17116/patol20238502127

34. Wang S.S., Bandopadhayay P., Jenkins M.R. Towards immunotherapy for pediatric brain tumors. Trends Immunol 2019;40(8):748–61. DOI: 10.1016/j.it.2019.05.009

35. Hwang E.I., Sayour E.J., Flores C.T. et al. The current landscape of immunotherapy for pediatric brain tumors. Nat Cancer 2022;3(1):11–24. DOI: 10.1038/s43018-021-00319-0

36. Sie M., den Dunnen W.F., Hoving E.W., de Bont E.S. Antiangiogenic therapy in pediatric brain tumors: an effective strategy? Crit Rev Oncol Hematol 2014;89(3):418–32. DOI: 10.1016/j.critrevonc.2013.09.005.

37. Crotty E.E., Leary S.E.S., Geyer J.R. et al. Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children’s Hospital experience. J Neurooncol 2020;148(3):607–17. DOI: 10.1007/s11060-020-03558-w

38. Jones D.T.W., Kieran M.W., Bouffet E. et al. Pediatric low-grade gliomas: next biologically driven steps. Neuro Oncol 2018;20(2):160–73. DOI: 10.1093/neuonc/nox141

39. De Blank P., Bandopadhayay P., Haas-Kogan D. et al. Management of pediatric low-grade glioma. Curr Opin Pediatr 2019;31(1):21–7. DOI: 10.1097/MOP.0000000000000717

40. FDA approves dabrafenib with trametinib for pediatric patients with low-grade glioma with a BRAF V600E mutation. Available at: https://www.fda.gov/drugs/resources-information-approveddrugs/fda-approves-dabrafenib-trametinib-pediatric-patients-lowgrade-glioma-braf-v600e-mutation

41. Lassaletta A., Scheinemann K., Zelcer S.M. et al. Phase II weekly vinblastine for chemotherapy-naïve children with progressive low-grade glioma: a Canadian Pediatric Brain Tumor Consortium Study. J Clin Oncol Off J Am Soc Clin Oncol 2016;34(29):3537–43.

42. Bitterman D.S., MacDonald S.M., Yock T.I. et al. Revisiting the role of radiation therapy for pediatric low-grade glioma. J Clin Oncol Off J Am Soc Clin Oncol 2019;37(35):3335–9. DOI: 10.1200/JCO.19.01270

43. Fangusaro J., Onar-Thomas A., Poussaint T.Y. et al. A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study. Neuro Oncol 2021;23(10):1777–88. DOI: 10.1093/neuonc/noab047

44. Fangusaro J., Onar-Thomas A., Young Poussaint T. et al. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol 2019;20(7):1011–22. DOI: 10.1016/S1470-2045(19)30277-3

45. Bouffet E., Hansford J., Garré M.L. et al. Primary analysis of a phase II trial of dabrafenib plus trametinib (dab + tram) in BRAF V600–mutant pediatric low-grade glioma (pLGG). J Clin Oncol 2022;40(17 Suppl):LBA2002–LBA2002. DOI: 10.1200/JCO.2022.40.17_suppl.LBA2002

46. Guerreiro Stucklin A.S., Ryall S., Fukuoka K. et al. Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nat Commun 2019;10(1):4343. DOI: 10.1038/s41467-019-12187-5

47. Ostrom Q.T., Price M., Ryan K. et al. CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018. Neuro Oncol 2022;24(Suppl 3):iii1–iii38. DOI: 10.1093/neuonc/noac161

48. Cocito C., Martin B., Giantini-Larsen A.M. et al. Leptomeningeal dissemination in pediatric brain tumors. Neoplasia 2023;39:100898. DOI: 10.1016/j.neo.2023.100898

49. Cohen K.J., Pollack I.F., Zhou T. et al. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro Oncol 2011;13(3):317–23. DOI: 10.1093/neuonc/noq191

50. Cohen K.J., Heideman R.L., Zhou T. et al. Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children’s Oncology Group. Neuro Oncol 2011;13(4):410–6. DOI: 10.1093/neuonc/noq205.

51. Jakacki R.I., Cohen K.J., Buxton A. et al. Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: a report of the Children’s Oncology Group ACNS0423 study. Neuro Oncol 2016;18(10):1442–50. DOI: 10.1093/neuonc/now038

52. Hoffman L.M., Geller J., Leach J. et al. TR-14A Feasibility and randomized phase II study of vorinostat, bevacizumab, or temozolomide during radiation followed by maintenance chemotherapy in newly-diagnosed pediatric high-grade glioma: Children Oncology Group study ACNS0822. Neuro Oncol 2015;17(Suppl 3):iii39–iii40. DOI: 10.1093/neuonc/nov061.159

53. Su J.M., Kilburn L.B., Mansur D.B. et al. Phase I/II trial of vorinostat and radiation and maintenance vorinostat in children with diffuse intrinsic pontine glioma: a Children’s Oncology Group report. Neuro Oncol 2022;24(4):655–64. DOI: 10.1093/neuonc/noab188

54. Karajannis M., Onar-Thomas A., Baxter P. et al. HGG-06. Phase 2 study of veliparib and local irradiation, followed by maintenance veliparib and temozolomide, in patients with newly diagnosed highgrade glioma without H3 K27M or BRAF mutations: a report from the Children's Oncology Group ACNS1721 study. Neuro Oncol 2022;24(Suppl 1):i60–1. DOI: 10.1093/neuonc/noac079.222

55. Das A., Tabori U., Sambira Nahum L.C. et al. Efficacy of nivolumab in pediatric cancers with high mutation burden and mismatch-repair deficiency. Clin Cancer Res 2023;29(23):4770–83. DOI: 10.1158/1078-0432.CCR-23-0411

56. Packer R.J., Gajjar A., Vezina G. et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 2006;24(25):4202–8. DOI: 10.1200/JCO.2006.06.4980

57. Jakacki R.I., Burger P.C., Zhou T. et al. Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a Children’s Oncology Group Phase I/II study. J Clin Oncol 2012;30(21):2648–53. DOI: 10.1200/JCO.2011.40.2792

58. Gajjar A., Robinson G.W., Smith K.S. et al. Outcomes by clinical and molecular features in children with medulloblastoma treated with risk-adapted therapy: results of an international phase III trial (SJMB03). J Clin Oncol 2021;39(7):822–35. DOI: 10.1200/JCO.20.01372

59. Michalski J.M., Janss A.J., Vezina L.G. et al. Children’s Oncology Group phase III trial of reduced-dose and reduced-volume radiotherapy with chemotherapy for newly diagnosed average-riskmedulloblastoma. J Clin Oncol 2021;39(24):2685–97. DOI: 10.1200/JCO.20.02730

60. Leary S.E.S., Packer R.J., Li Y. et al. Efficacy of carboplatin and isotretinoin in children with high-risk medulloblastoma: a randomized clinical trial from the Сhildren’s Oncology Group. JAMA Oncol 2021;7(9):1313–21. DOI: 10.1001/jamaoncol.2021.2224

61. Lafay-Cousin L., Bouffet E., Strother D. et al. Phase II study of nonmetastatic desmoplastic medulloblastoma in children younger than 4 years of age: a report of the Children’s Oncology Group (ACNS1221). J Clin Oncol 2020;38(3):223–31. DOI: 10.1200/JCO.19.00845

62. Mazewski C., Kang G., Kellie S. et al. MBCL-34. Efficacy of methotrexate (MTX) according to molecular sub-type in young children with medulloblastoma (MB): a report from Children’s Oncology Group Phase III trial ACNS0334. Neuro Oncol 2020;22(Suppl 3):iii396. DOI: 10.1093/neuonc/noaa222.510

63. Shih D.J.H., Northcott P.A., Remke M. et al. Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol Off J Am Soc Clin Oncol 2014;32(9):886–96. DOI: 10.1200/JCO.2013.50.9539

64. Goschzik T., Schwalbe E.C., Hicks D. et al. Prognostic effect of whole chromosomal aberration signatures in standard-risk, non-WNT/non-SHH medulloblastoma: a retrospective, molecular analysis of the HIT-SIOP PNET 4 trial. Lancet Oncol 2018;19(2):1602–16. DOI: 10.1016/S1470-2045(18)30532-1

65. Lazow M.A., Palmer J.D., Fouladi M., Salloum R. Medulloblastoma in the modern era: review of contemporary trials, molecular advances, and updates in management. Neurotherapeutics 2022;19(6):1733–51. DOI: 10.1007/s13311-022-01273-0

66. Pajtler K.W., Mack S.C., Ramaswamy V. et al. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol (Berl) 2017;133(1):5–12. DOI: 10.1007/s00401-016-1643-0

67. Pajtler K.W., Witt H., Sill M. et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 2015;27(5):728–43. DOI: 10.1016/j.ccell.2015.04.002.

68. Ghasemi D.R., Sill M., Okonechnikov K. et al. MYCN amplification drives an aggressive form of spinal ependymoma. Acta Neuropathol (Berl) 2019;138(6):1075–89. DOI: 10.1007/s00401-019-02056-2

69. Panwalkar P., Clark J., Ramaswamy V. et al. Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. Acta Neuropathol (Berl) 2017;134(5):705–14. DOI: 10.1007/s00401-017-1752-4

70. Merchant T.E., Bendel A.E., Sabin N.D. et al. Conformal radiation therapy for pediatric ependymoma, chemotherapy for incompletely resected ependymoma, and observation for completely resected, supratentorial ependymoma. J Clin Oncol Off J Am Soc Clin Oncol 2019;37(12):974–83. DOI: 10.1200/JCO.18.01765


Review

For citations:


Shebanova E.O., Kurmanova A.O., Sevyan N.V., Prozorenko E.V., Kirsanov V.Yu. Diagnosis and treatment of pediatric brain tumors. MD-Onco. 2025;5(1):47-58. (In Russ.) https://doi.org/10.17650/2782-3202-2025-5-1-47-58

Views: 131


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2782-3202 (Print)
ISSN 2782-6171 (Online)