Surgery and radiotherapy strategies at first relapse of pediatric intracranial ependymoma: an Italian retrospective study integrating molecular subgrouping.

PURPOSE: The prognosis of intracranial ependymoma correlates to complete surgery followed by focal irradiation(RT).No standard therapies exist at relapse. METHODS: We analyzed relapsed patients between 2009 and 2023 both diagnosed in our institution as well as referred. RESULTS: Patients were 33 (females 12), median age 3.3 years. All treated according to AIEOP1st -2nd or SIOP 2nd protocol, i.e., operated and focally irradiated; some had chemotherapy (VEC or VEC/cisplatin + VCR) either after surgery(#13 for residual disease) or after radiotherapy(#10)0.25 tumors originated in posterior fossa,29 were grade 3,23 were tumor-free at RT. Relapses appeared at median 31 months after diagnosis: local in 22 cases, disseminated/combined in 11.21 tumors classified as PFA,8 as RELA/ZFTA.19 patients were again completely operated,16 received hypofractionated reirradiation at 8–16 Gy in 2/4 fractions,6 standard re-RT at 18–54 Gy,10 36 Gy craniospinal irradiation for dissemination; one no treatment. We evaluated the first EFS, OS, and post-first relapse EFS/OS (EFS2/OS2). Median EFS, OS, EFS2 and OS2 were 31.1,66.4,13.6 and 31.5 months, respectively. EFS was positively associated to female sex, grade 3,complete resection at diagnosis/at relapse(also of single metastatic relapse). RELA/ZFTA molecular subgroup tumors affected positively on OS2. Supratentorial location and RELA/ZFTA showed an association that approached statistical significance on EFS2. Type of re-RT had no impact on analyses, with craniospinal radiotherapy adopted only for disseminated/combined relapse. In mutivariable analysis RELA/ZFTA subgroup and complete resection at relapse were associated with improved OS. 13/33 patients survived more than 7 years: 9 alive and 7 tumor-free. CONCLUSIONS: Complete resection is a therapeutic resource also after relapse, ideal re-RT has to be found; outcome differed by molecular subgroup in our cohort.