TY - JOUR
T1 - Second series by the Italian Association of Pediatric Hematology and Oncology of children and adolescents with intracranial ependymoma: an integrated molecular and clinical characterization with a long-term follow-up
AU - Massimino, Maura
AU - Barretta, Francesco
AU - Modena, Piergiorgio
AU - Witt, Hendrik
AU - Minasi, Simone
AU - Pfister, Stefan M.
AU - Pajtler, Kristian W.
AU - Antonelli, Manila
AU - Gandola, Lorenza
AU - Garrè, Maria Luisa
AU - Bertin, Daniele
AU - Mastronuzzi, Angela
AU - Mascarin, Maurizio
AU - Quaglietta, Lucia
AU - Viscardi, Elisabetta
AU - Sardi, Iacopo
AU - Ruggiero, Antonio
AU - Pollo, Bianca
AU - Buccoliero, Annamaria
AU - Boschetti, Luna
AU - Schiavello, Elisabetta
AU - Chiapparini, Luisa
AU - Erbetta, Alessandra
AU - Morra, Isabella
AU - Gessi, Marco
AU - Donofrio, Vittoria
AU - Patriarca, Carlo
AU - Giangaspero, Felice
AU - Johann, Pascal
AU - Buttarelli, Francesca Romana
PY - 2021
Y1 - 2021
N2 - Background. A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We re-analyzed the series after a median of 119 months, adding retrospectively patients' molecular features.Methods. Follow-up of all patients was updated. DNA copy number analysis and gene-fusion detection could be completed for 94/160 patients, methylation classification for 68.Results. Progression-free survival (PFS) and overall survival (OS) at 5/10 years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 mo), surviving after relapse no longer than those relapsing earlier (0-5 y). On multivariable analysis a better PFS was associated with grade II tumor and complete surgery at diagnosis and/or at radiotherapy; female sex and complete resection showed a positive association with OS. Posterior fossa (PF) tumors scoring >= 0.80 on DNA methylation analysis were classified as PFA (n = 41) and PFB (n = 9). PFB patients had better PFS and OS. Eighteen/32 supratentorial tumors were classified as RELA, and 3 as other molecular entities (anaplastic PXA, LGG MYB, HGNET). RELA had no prognostic impact. Patients with 1q gain or cyclin-dependent kinase inhibitor 2A (CDKN2A) loss had worse outcomes, included significantly more patients >3 years old (P = 0.050) and cases of dissemination at relapse (P = 0.007).Conclusions. Previously described prognostic factors were confirmed at 10-year follow-up. Late relapses occurred in 6.2% of patients. Specific molecular features may affect outcome: PFB patients had a very good prognosis; 1q gain and CDKN2A loss were associated with dissemination. To draw reliable conclusions, modern ependymoma trials need to combine diagnostics with molecular risk stratification and long-term follow-up.
AB - Background. A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We re-analyzed the series after a median of 119 months, adding retrospectively patients' molecular features.Methods. Follow-up of all patients was updated. DNA copy number analysis and gene-fusion detection could be completed for 94/160 patients, methylation classification for 68.Results. Progression-free survival (PFS) and overall survival (OS) at 5/10 years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 mo), surviving after relapse no longer than those relapsing earlier (0-5 y). On multivariable analysis a better PFS was associated with grade II tumor and complete surgery at diagnosis and/or at radiotherapy; female sex and complete resection showed a positive association with OS. Posterior fossa (PF) tumors scoring >= 0.80 on DNA methylation analysis were classified as PFA (n = 41) and PFB (n = 9). PFB patients had better PFS and OS. Eighteen/32 supratentorial tumors were classified as RELA, and 3 as other molecular entities (anaplastic PXA, LGG MYB, HGNET). RELA had no prognostic impact. Patients with 1q gain or cyclin-dependent kinase inhibitor 2A (CDKN2A) loss had worse outcomes, included significantly more patients >3 years old (P = 0.050) and cases of dissemination at relapse (P = 0.007).Conclusions. Previously described prognostic factors were confirmed at 10-year follow-up. Late relapses occurred in 6.2% of patients. Specific molecular features may affect outcome: PFB patients had a very good prognosis; 1q gain and CDKN2A loss were associated with dissemination. To draw reliable conclusions, modern ependymoma trials need to combine diagnostics with molecular risk stratification and long-term follow-up.
KW - children
KW - follow-up
KW - intracranial ependymoma
KW - molecular events
KW - prognosis
KW - children
KW - follow-up
KW - intracranial ependymoma
KW - molecular events
KW - prognosis
UR - http://hdl.handle.net/10807/223494
U2 - 10.1093/neuonc/noaa257
DO - 10.1093/neuonc/noaa257
M3 - Article
SN - 1522-8517
VL - 23
SP - 848
EP - 857
JO - Neuro-Oncology
JF - Neuro-Oncology
ER -