2022 Background: NB metastatic to the CNS (NB-CNS) is difficult to control. We describe a salvage regimen incorporating intra- Ommaya RIT delivered to the CSF. Methods: 37 patients (pts) with NB-CNS (parenchymal masses and/or leptomeningeal [LM] carcinomatosis) treated at MSKCC from 1988 through 2006 were reviewed. Nine (group #1) of 37 pts developed NB-CNS metastasis (median age 3.8 years) and were treated with a salvage regimen: resection of parenchymal masses, 2160 cGy craniospinal irradiation (CSI), intravenous irinotecan and oral temozolomide, and RIT with 131I-8H9 and or 131I-3F8 targeting tumor associated antigens on phase I/II studies. Immunotherapy (intravenous anti-GD2 monoclonal antibody 3F8 plus subcutaneous GM-CSF) was also given for systemic control. Survival was compared to the other 28 (group #2) pts who developed NB-CNS (median age 4.2 years) treated with combinations of surgery, chemotherapy, and radiation but without CSI + RIT. Results: All 37 pts had high risk disease at initial diagnosis of NB. 9 of 9 group #1 pts had marrow and/or bony involvement; 6 of 9 had MYCN amplification and 5 of 9 had serum LDH >1500 U/ml. All had intensive chemotherapy and radiotherapy prior to CNS relapse. Despite this, the CNS salvage regimen was well-tolerated. Myelosuppression following CSI and chemotherapy was common; 2 pts received stem cell support. All 9 pts in the RIT group are alive and well, disease-free at 3+, 11+, 15+, 18+, 18+, 20+, 22+, 31+, 42+ months since CNS relapse. In contrast, pts in group #2 had a median time to death of 5.5 months, (p<0.0001) for survival by Kaplan-Meier analysis. Conclusion: Similar to CNS metastases in most other solid tumors, conventional therapies have been ineffective for NB-CNS. The addition of RIT using 131I-3F8 or 131I-8H9 is well-tolerated and improves the prognosis for these high risk patients. No significant financial relationships to disclose.