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. Issue 5 (2nd November 2020)

• Record Type: Journal Article
• Authors: Massimino, Maura; Barretta, Francesco; Modena, Piergiorgio; Witt, Hendrik; Minasi, Simone; Pfister, Stefan M; Pajtler, Kristian W; Antonelli, Manila; Gandola, Lorenza; Luisa Garrè, Maria; Bertin, Daniele; Mastronuzzi, Angela; Mascarin, Maurizio; Quaglietta, Lucia; Viscardi, Elisabetta; Sardi, Iacopo; Ruggiero, Antonio; Pollo, Bianca; Buccoliero, Annamaria; Boschetti, Luna; Schiavello, Elisabetta; Chiapparini, Luisa; Erbetta, Alessandra; Morra, Isabella; Gessi, Marco; Donofrio, Vittoria; Patriarca, Carlo; Giangaspero, Felice; Johann, Pascal; Buttarelli, Francesca Romana
• Is Part Of: Neuro-oncology. Volume 23:Issue 5(2021)
• Page Start: 848
• Page End: 857
• Publication Date: 2020-11-02
• Subjects: children -- follow-up -- intracranial ependymoma -- molecular events -- prognosis; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa257
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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.