Maura Massimino1, Francesco Barretta2, Piergiorgio Modena3, Hendrik Witt4, Simone Minasi5, Stefan M Pfister4, Kristian W Pajtler4, Manila Antonelli6, Lorenza Gandola7, Maria Luisa Garrè8, Daniele Bertin9, Angela Mastronuzzi10, Maurizio Mascarin11, Lucia Quaglietta12, Elisabetta Viscardi13, Iacopo Sardi14, Antonio Ruggiero15, Bianca Pollo16, Annamaria Buccoliero17, Luna Boschetti11, Elisabetta Schiavello11, Luisa Chiapparini18, Alessandra Erbetta18, Isabella Morra19, Marco Gessi20, Vittoria Donofrio21, Carlo Patriarca22, Felice Giangaspero23, Pascal Johann4, Francesca Romana Buttarelli5. 1. Pediatric Radiotherapy, Oncology Referral Center, Aviano, Italy. 2. Medical Statistics, Biometry and Bioinformatics, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan, Italy. 3. Laboratory of Genetics, Sant'Anna General Hospital, Como, Italy. 4. Hopp-Children's Cancer Center Heidelberg, German Cancer Research Center, German Cancer Consortium , Heidelberg, Germany. 5. Departments of Neurology and Psychiatric, La Sapienza University, Rome, Italy. 6. Radiological, Oncological and Anatomo-Pathological Sciences, La Sapienza University, Rome, Italy. 7. Pediatric Radiotherapy, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan, Italy. 8. Neuroncology and Neurosurgery Unit, Giannina Gaslini Institute, Genova, Italy. 9. Pediatric Onco-Hematology, Units, Regina Margherita Children's Hospital, Torino, Italy. 10. Pediatric Hematology and Oncology Department, Bambino Gesù Pediatric Hospital, Rome, Italy. 11. Departments of Pediatric, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan, Italy. 12. Departments of Pediatric Oncology, Santobono-Pausillipon Hospital, Naples, Italy. 13. Pediatric Oncology, Padova University, Italy. 14. Neuroncology, Units, Meyer Pediatric Hospital, Firenze, Italy. 15. Pediatric Oncology, Units, A. Gemelli Polyclinic, Rome, Italy. 16. Pathology, Pozzilli, Italy. 17. Pathology, Units, Meyer Pediatric Hospital, Firenze, Italy. 18. Radiology, Pozzilli, Italy. 19. Pathology, Units, Regina Margherita Children's Hospital, Torino, Italy. 20. Pathology, Units, Carlo Besta Neurological Institute, Milan, Italy. 21. Pathology, Santobono-Pausillipon Hospital, Naples, Italy. 22. Pathology Unit, Sant'Anna General Hospital, Como, Italy. 23. IRCCS Neuromed, Pozzilli, Italy.
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.
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.
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