10012 Background: Circulating tumor DNA (ctDNA) is detectable in children with neuroblastoma. Less is known about how levels change during treatment and the implications of these changes. We evaluated ctDNA pre- and post- 131I-metaiodobenzylguanidine (MIBG) therapy. Methods: We utilized plasma samples from NANT11-01 (NCT02035137), a multi-center, open label, randomized phase II clinical trial evaluating MIBG with or without radiation sensitizers for patients with relapsed or refractory neuroblastoma. Plasma was collected at Baseline prior to MIBG, 72 hours (Hr72), 96 hours (Hr96), 15 days after MIBG (D15), and prior to a second course among patients without progression who received a second course (C2). Samples were analyzed for percent ctDNA levels using ultra-low passage whole genome sequencing. We evaluated associations between ctDNA findings with baseline disease measures of percent involvement in bone marrow, Curie score, and RECIST disease sum of diameters as well as overall response by NANT Response Criteria v1.2 (complete response or partial response coded as responders). Results: Eighty-four patients had a baseline sample and were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32% (range 3.9-91%). Baseline ctDNA levels showed a significant positive correlation with percent involvement in bone marrow (r=0.37; p=0.0004) and Curie score (r=0.26; p = 0.018), but not RECIST sum of diameters for soft tissue sites (r=0.065; p=0.56). Following therapy, the proportions of patients with detectable ctDNA were: Hr72 47% (34/73; median level 28%); Hr96 50% (26/52; median 28%); D15 33% (7/21; median 4%); and C2 14% (3/21; median 50%). Rate of ctDNA detection was similar between responders and non-responders at baseline, Hr72, and Hr96, but lower among responders at D15 and C2 (Table). Among the 21 patients with C2 data, ctDNA levels were either undetectable (n=18) or lower than Cycle 1 Baseline (n=3). Among patients with detectable baseline ctDNA, the median relative ctDNA level at Hr72 (Hr72 ctDNA/baseline ctDNA) for non-responders was 0.87 (n=24) vs. 1.16 for responders (n=7). In contrast, the median relative ctDNA level at C2 for non-responders was 0.56 (n=4) vs. 0 for responders (n=4). Conclusions: ctDNA is detectable in a substantial proportion of patients with relapsed / refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints (Hr72 and Hr96) are less informative, whereas ctDNA becomes undetectable at D15 and C2 more commonly in patients with clinical response.[Table: see text]