Journal Article

DKFZ-2023-01314

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.

Kolodziejczak, A. (First author)DKFZ* ; Guerrini-Rousseau, L. ; Planchon, J. M. ; Ecker, J.DKFZ* ; Selt, F.DKFZ* ; Mynarek, M. ; Obrecht, D. ; Sill, M.DKFZ* ; Autry, R.DKFZ* ; Zhao, E.DKFZ* ; Hirsch, S.DKFZ* ; Amouyal, E. ; Dufour, C. ; Ayrault, O. ; Torrejon, J. ; Waszak, S. M. ; Ramaswamy, V. ; Pentikainen, V. ; Demir, H. A. ; Clifford, S. C. ; Schwalbe, E. C. ; Massimi, L. ; Snuderl, M. ; Galbraith, K. ; Karajannis, M. A. ; Hill, K. ; Li, B. K. ; Walsh, M. ; White, C. L. ; Redmond, S. ; Loizos, L. ; Jakob, M. ; Kordes, U. R. ; Schmid, I. ; Hauer, J. ; Blattmann, C. ; Filippidou, M. ; Piccolo, G. ; Scheurlen, W. ; Farrag, A. ; Grund, K. ; Sutter, C. ; Pietsch, T. ; Frank, S. ; Schewe, D. M. ; Malkin, D. ; Ben-Arush, M. ; Sehested, A. ; Wong, T.-T. ; Wu, K.-S. ; Liu, Y.-L. ; Carceller, F. ; Mueller, S. ; Stoller, S. ; Taylor, M. D. ; Tabori, U. ; Bouffet, E. ; Kool, M.DKFZ* ; Sahm, F.DKFZ* ; von Deimling, A.DKFZ* ; Korshunov, A.DKFZ* ; von Hoff, K. ; Kratz, C. P. ; Sturm, D.DKFZ* ; Jones, D.DKFZ* ; Rutkowski, S. ; van Tilburg, C. M.DKFZ* ; Witt, O.DKFZ* ; Bougeard, G. ; Pajtler, K.DKFZ* ; Pfister, S.DKFZ* ; Bourdeaut, F. ; Milde, T. (Last author)DKFZ*

2023
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noad114

Abstract: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients.In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated.The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup 'SHH_3' (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received post-operative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively).LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.

Keyword(s): Li-Fraumeni syndrome ; TP53 ; medulloblastoma ; survival

Note: #EA:B310#LA:B310# / 2023 Dec 8;25(12):2273-2286

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Contributing Institute(s):

1. KKE Pädiatrische Onkologie (B310)
2. DKTK HD zentral (HD01)
3. B062 Pädiatrische Neuroonkologie (B062)
4. KKE Neuropathologie (B300)
5. Pädiatische Gliomforschung (B360)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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