The AIEOP 2nd series of children and adolescents intracranial Ependymoma. An integrated molecular and clinical characterization with a long-term follow-up

Maura Massimino, Francesco Barretta, Piergiorgio Modena, Hendrik Witt, Simone Minasi, Stefan M Pfister, Kristian W Pajtler, Manila Antonelli, Lorenza Gandola, Maria Luisa Garrè, Daniele Bertin, Maurizio Mascarin, Angela Mastronuzzi, Lucia Quaglietta, Elisabetta Viscardi, Iacopo Sardi, Antonio Ruggiero, Bianca Pollo, Annamaria Buccoliero, Luna BoschettiElisabetta Schiavello, Luisa Chiapparini, Alessandra Erbetta, Isabella Morra, Marco Gessi, Vittoria Donofrio, Carlo Patriarca, Felice Giangaspero, Pascal Johann, Francesca Romana Buttarelli

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We reanalyzed the series after a median 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: PFS and OS at five/ten years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 months), surviving after relapse no longer than those relapsing earlier (0-5 years). On multivariable analysis a better PFS was associated with grade 2 tumor and complete surgery at diagnosis and/or at RT; 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 (41) and PFB (8). PFB patients had better PFS and OS. Eighteen/32 supratentorial(ST) 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 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.

Original languageEnglish
JournalNeuro-Oncology
DOIs
Publication statusE-pub ahead of print - Nov 2 2020

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