Long-Term Follow-Up Of Aieop 2nd Series Of Children And Adolescent With Primary Intracranial (St:Supratentorial; Pf: Posterior Fossa) Ependymoma And Methylation Groups Re-Analyses

Abstract BACKGROUND This 2002–2014 Italian prospective study stratified 160 patients by surgical resection (complete=NED/incomplete=ED) and centrally-reviewed grade. Grade2/NED patients received focal radiotherapy (RT) up to 59.4Gy, Grade3/NED received 4 courses of VEC(vincristine,etoposide,cyclophosphamide) after RT.ED patients received 1–4 VEC courses, second-look surgery, 59.4 Gy+8Gy boost on measurable residue. METHODS We re-analyzed data at 115 months follow-up including methylation profile on available samples. RESULTS Global PFS/OS at 5/10 years were 66/59% and 80/74%, respectively. Of the 64 relapsers at median 20 months, 53 died at median 37/18 months after diagnosis/relapse, respectively.10/64 relapsed after 5 years (66–126 months); 4 died, relapse was local in 8/10, metastatic 1, combined 1;5/10 patients were below age 3, 5 females, 8 PF tumors. Their survival post-relapse was not longer than earlier relapsers’. At univariable analysis, age over 3 years, female sex, complete surgery, grade 2, no shunt confirmed better PFS/OS. 66/95 analyzed tumors received a score >0.80 through the DNA methylation-based central nervous system tumor classifier: 41/8 as PFA/PFB, respectively,14/17 ST as RELA-positive (3 scored for other molecular entities i.e. anaplastic PXA, LGG MYB, HGNET). Prognostic factors were equally distributed among PFA/PFB groups,1 only group B patient relapsed locally at 96 months. CONCLUSIONS Already published prognostic factors remained at long-term follow-up;6.2% patients had late relapses. OS after relapse was not better in late relapsers. Group B confirmed better prognosis but all patients had received «at least» adjuvant RT. Modern ependymoma trials need long follow-up to draw firm conclusions.