Whole neuraxis irradiation to address central nervous system (CNS) relapse in high-risk neuroblastoma (NB)

Abstract

10050 Background: CNS relapse in high-risk NB is on the rise as extracranial disease control improves. Management of CNS relapse with radiotherapy (RT) that does not address the entire neuraxis has been ineffective in preventing further progression and ultimate death. The purpose of the present study is to describe the use of craniospinal irradiation (CSI) for CNS relapse in high-risk NB and compare outcomes to a historical cohort of patients who did not receive CSI. Methods: A retrospective query identified 24 children with high- risk NB treated at MSKCC since 1987 who received RT for CNS relapse. All patients received appropriate initial therapies and were in remission at the time of CNS recurrence. 14 patients received CSI, and 10 received focal RT that did not address the entire neuraxis. CSI was delivered to a median dose of 2160 cGy, and 10 patients received a boost to a median dose of 2520 cGy. Of those who underwent CSI, 13 (93%) received intrathecal (IT) immunotherapy with 131I-8H9 or 131I-3F8. None of the patients in the non-CSI cohort received IT immunotherapy. Results: The demographic and relapse characteristics were similar between the two groups with the exception that patients who underwent CSI represented a more modern cohort. The age at and time to CNS relapse was 5 and 1.5 years, respectively, in both cohorts. At a median follow-up of 18.3 months (range 1.5–53) after CNS relapse, 10 (71%) patients in the CSI group are alive without evidence of disease. In contrast, all 10 patients in the non-CSI cohort died of disease at a median of 8.1 months (range 4.2–12.9). One patient in the CSI cohort died 1.5 years after CNS relapse of progressive leptomeningeal disease; this was also the only patient in that cohort who did not receive IT immunotherapy. One patient in the CSI cohort died 22 months after CNS relapse of unrelated causes. Two patients developed bone recurrence, but remain free of CNS disease. Conclusions: Based on this small cohort of patients, low-dose CSI in conjunction with IT immunotherapy provides durable CNS remissions and improved survival relative to the experience with focal RT and conventional therapies alone. Further evaluation of long-term NB survivors after CSI is warranted to determine the unique long-term treatment consequences for this young patient cohort. No significant financial relationships to disclose.