Introduction: Incidence of central nervous system (CNS) relapses in high-risk neuroblastoma patients has not been clearly defined yet. In this study, we aimed to identify the incidence and the risk factors of CNS recurrences at first relapse in patients with high-risk neuroblastoma.
Methods: Patients with stage 4 > 12 months and/or MYCN amplified tumors treated in the high-risk neuroblastoma HR-NBL1/SIOPEN trial were studied. Characteristics at diagnosis, treatment and pattern of first relapse were analyzed. Central review of imaging was performed to confirm CNS metastases. Cumulative incidences of CNS-relapses were estimated taking into account the completing risks of Non-CNS relapses and Death. The statistical comparison was done with Gray test.
Results: Among the 2209 patients included into the HR-NBL/SIOPEN trial, 1323 patients relapsed and 64/1323 had CNS metastases. Five-year incidence of CNS recurrence was 3%±0% for the whole population, and 5%±1% of all relapses. CNS was the only site of relapse in 37/64 patients. Time to relapse was 1.03 and 1.2 years for CNS recurrences and other recurrences, respectively (p=0.117). Post-relapse overall survival (OS) was worse (p=0.057) in children with CNS relapse. Age, gender, stage, MYCN status and bone marrow, bone and lung involvement at diagnosis had no impact on the risk of CNS relapses; only liver metastases (p=0.001) and the involvement of several metastatic compartments at diagnosis (p<0.001) correlated to CNS relapse. The HDC regimen (Busulfan-Melphalan (Bu-Mel) vs Carboplatin-Etoposide-Melphalan (CEM)) had no impact on the incidence of the CNS recurrences (p= 0.649).
Conclusions: The risk of CNS recurrence in patients with HR neuroblastoma is 3% at 5 years after diagnosis. Since the CNS evaluation is not routinely performed in the current HR-NBL1/SIOPEN protocol, the real incidence of CNS relapses might be higher and should be prospectively evaluated in order to establish the need of a prophylactic strategy.