Results of a multicenter study of the treatment of WNT medulloblastomas in children-Reference-Cited by-同舟云学术

Results of a multicenter study of the treatment of WNT medulloblastomas in children

Published:2023-11-29 Issue:3 Volume:10 Page:22-40
ISSN:2413-5496
Container-title:Russian Journal of Pediatric Hematology and Oncology
language:
Short-container-title:Ross. ž. det. gematol. onkol.

Author:

Zheludkova O. G.¹^ORCID,Olkhova L. V.²^ORCID,Ryzhova M. V.³^ORCID,Shishkina L. V.³^ORCID,Kushel Yu. V.³^ORCID,Melikyan A. G.³^ORCID,Gorelyshev S. K.³^ORCID,Golanov A. V.³^ORCID,Trunin Yu. Yu.³^ORCID,Vorobyov N. A.⁴^ORCID,Plakhotina N. A.⁵^ORCID,Boiko K. F.⁵^ORCID,Levashov A. S.⁶^ORCID,Polushkina O. B.⁷^ORCID,Korneev D. Yu.⁷,Postnikova T. V.⁷^ORCID,Borodina I. D.⁸^ORCID,Kislyakov A. N.⁹^ORCID,Skobeev D. A.⁹^ORCID,Gorbatykh S. V.⁹^ORCID,Ozerov S. S.⁹^ORCID,Skorobogatova E. V.²^ORCID,Inyushkina E. V.¹⁰^ORCID,Popov V. E.¹¹^ORCID,Mushinskaya M. V.¹²^ORCID,Kovalenko S. G.¹³^ORCID,Pogorelov D. N.¹⁴^ORCID,Yudina N. B.¹⁵^ORCID,Zaychikov A. N.¹⁶^ORCID,Bayramgulov R. R.¹⁷,Sakun D. L.¹⁸^ORCID,Minkina L. M.¹⁹^ORCID,Matsekha E. P.²⁰,Tsyrenova N. V.²¹^ORCID,Grishina E. N.²²,Borisova M. V.²³^ORCID,Matytsyn A. F.²⁴,Fedorova T. B.²⁵,Dinikina Yu. V.²⁶^ORCID,Martynenko V. V.²⁷^ORCID,Shapochnik A. P.²⁸^ORCID,Yunusova I. M.²⁹,Mitrofanov V. A.³⁰^ORCID,Rumyantsev A. A.³¹,Fisyun I. V.³²^ORCID,Timofeeva V. N.³³^ORCID,Shamin A. V.³⁴,Markovsky A. M.³⁵,Bykova G. V.³⁶,Popova N. A.³⁷,Kochukova N. V.³⁸,Ostanina E. A.²⁵,Pshenichnikova A. A.³⁹^ORCID

Affiliation:

1. Scientific and Practical Center for Specialized Medical Care for Children named after V.F. Voyno-Yasenetsky Moscow Healthcare Department; Diagnostic and Treatment Center of International Institution for Biological Systems named after Sergey Berezin

2. Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

3. N.N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Health of Russia

4. Diagnostic and Treatment Center of International Institution for Biological Systems named after Sergey Berezin; Saint-Petersburg State University; North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia

5. Diagnostic and Treatment Center of International Institution for Biological Systems named after Sergey Berezin

6. N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia

7. Scientific and Practical Center for Specialized Medical Care for Children named after V.F. Voyno-Yasenetsky Moscow Healthcare Department

8. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia

9. Morozovskaya Children’s Clinical Hospital of the Moscow City Healthcare Department

10. Moscow Regional Oncological Dispensary

11. Moscow Regional Research and Clinical Institute (“MONIKI”)

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

13. Chelyabinsk Regional Children’s Hospital

14. Lipetsk Regional Children’s Hospital

15. Voronezh Regional Children’s Clinical Hospital No 1

16. Regional Children’s Clinical Hospital No. 1

17. Republican Children’s Clinical Hospital of Ministry of Health of Republic of Bashkortostan

18. Crimean Republican Pediatric Clinical Hospital

19. Regional Children’s Clinical Hospital No. 1

20. Trans-Baikal Regional Oncology Center

21. Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Buryatia

22. Children’s Republican Clinical Hospital Ministry of Health of the Republic of Tatarstan

23. Krasnoyarsk Regional Clinical Centre for Maternal and Child Health

24. Tambov Regional Children’s Hospital

25. Regional Children’s Clinical Hospital

26. Almazov National Medical Research Centre, Ministry o f Health o f Russia

27. Bryansk Regional Children’s Hospital

28. Orenburg Regional Clinical Oncology Hospital; Orenburg State Medical University, Ministry of Health of Russia

29. Children’s Republican Clinical Hospital named after N.M. Kuraev

30. Regional Children’s Clinical Hospital named after P.G. Vyzhletsov

31. Altai Regional Clinical Center for Maternal and Child Health

32. Scientific and Clinical Multidisciplinary Center of Medical Care for Mothers and Children named after Z.I. Kruglaya

33. Ulyanovsk Regional Children’s Clinical Hospital named after the political and public figure Y.F. Goryachev

34. Samara Regional Children’s Clinical Hospital named after N.N. Ivanovoy

35. Kuzbass Clinical Oncological Dispensary named after M.S. Rappoport

36. Stavropol Regional Children’s Clinical Hospital

37. Pediatric Oncohematological Center, Volgograd Regional Clinical Oncologic Dispensary

38. Regional Children’s Clinical Hospital named after N.N. Silishchevoy

39. Children’s Clinical Consulting and Diagnostic Center

Abstract

Medulloblastomas of the WNT molecular group (MB-WNT) represent the smallest group of MB and account for only 10 % of the total. This molecular group is characterized by a favorable prognosis. Given the aggressive treatment regimens for MB, reducing the intensity of therapy for prognostically favorable tumors seems justified. Purpose of the study – to demonstrate the results of treatment of children with MB-WNT and to determine the impact on survival of various prognostic factors. The study included 85 patients with MB-WNT under the age of 18 who received treatment and were followed up from 1993 to 2022. Median age at diagnosis was 10 years (min – 3, max – 17). All patients had classical MB. Metastatic spread of the tumor at the time of diagnosis was detected in 18 (21.2 %) patients, the presence of a residual tumor according to postoperative magnetic resonance imaging – in 32 (37.7 %). Somatic mutations in the TP53 gene were detected in 10 (7.1 %) patients, in the CTNNB1 gene – in 79 (92.9 %), in the APC gene – in 5 (5.9 %), chromosome 6 monosomy – in 76 (89.4 %) children. At the time of the analysis, 74 (87.1 %) patients were alive, 11 (12.9 %) patients died, a relapse was diagnosed in 6 (7.1 %) patients, of which 5 died from disease progression, 1 patient is alive in the second remission. One patient in long-term remission developed secondary meningioma 20 years after the diagnosis of MB. The 10-year progression-free survival (PFS) was 0.92. 5-year overall survival (OS) was 0.90, 10-year – 0.86. The median OS is 112 months. When analyzing the sample of patients with MB-WNT in our study, PFS and OS were statistically significantly higher in girls without metastatic tumor spread, with total resection of the tumor, stratified into the low-risk group, and in the absence of a somatic mutation in the TP53 gene in the tumor tissue. In multivariate analysis, PFS was influenced by the stage of the disease and the presence of a somatic mutation in the TP53 gene in the tumor tissue; on OS – only the presence of a somatic mutation in the TP53 gene in the tumor tissue.

Publisher

OOO Grafika

Subject

Oncology,Hematology,Pediatrics, Perinatology and Child Health

Reference38 articles.

1. Ostrom Q.T., Cioffi G., Waite K., Kruchko C., Barnholtz-Sloan J.S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018. Neuro Oncol. 2021;23(12 Suppl 2):iii1–iii105. doi: 10.1093/neuonc/noab200.

2. Johnston D.L., Keene D., Strother D., Taneva M., Lafay-Cousin L., Fryer C., Scheinemann K., Carret A.S., Fleming A., Afzal S., Wilson B., Bowes L., Zelcer S., Mpofu C., Silva M., Larouche V., Brossard J., Bouff et E. Survival Following Tumor Recurrence in Children With Medulloblastoma. J Pediatr Hematol Oncol. 2018;40(3):e159–e163. doi: 10.1097/MPH.0000000000001095.

3. Chintagumpala M., Gajjar A. Brain tumors. Pediatr Clin North Am. 2015;62(1):167–78. doi: 10.1016/j.pcl.2014.09.011.

4. Onodera S., Nakamura Y., Azuma T. Gorlin Syndrome: Recent Advances in Genetic Testing and Molecular and Cellular Biological Research. Int J Mol Sci. 2020;21(20):7559. doi: 10.3390/ijms21207559.

5. Langenberg K.P.S., Meister M.T., Bakhuizen J.J., Boer J.M., van Eijkelenburg N.K.A., Hulleman E., Ilan U., Looze E.J., Dierselhuis M.P., van der Lugt J., Breunis W., Schild L.G., Ober K., van Hooff S.R., Scheijde-Vermeulen M.A., Hiemcke-Jiwa L.S., Flucke U.E., Kranendonk M.E.G., Wesseling P., Sonneveld E., Punt S., Boltjes A., van Dijk F., Verwiel E.T.P., Volckmann R., Hehir-Kwa J.Y., Kester L.A., Koudijs M.M.J., Waanders E., Holstege F.C.P., Vormoor H.J., Hoving E.W., van Noesel M.M., Pieters R., Kool M., Stumpf M., Blattner-Johnson M., Balasubramanian G.P., Van Tilburg C.M., Jones B.C., Jones D.T.W., Witt O., Pfi ster S.M., Jongmans M.C.J., Kuiper R.P., de Krijger R.R., Wijnen M.H.W., den Boer M.L., Zwaan C.M., Kemmeren P., Koster J., Tops B.B.J., Goemans B.F., Molenaar J.J. Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'. Eur J Cancer. 2022;175:311–25. doi: 10.1016/j.ejca.2022.09.001.