Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma.

Abstract

10557 Background: This retrospective study sought to identify predictors of metastatic site failure (MSF) in patients with high-risk (HR) neuroblastoma (NB). Methods: Seventy-six patients with HR NB treated on prospective trials at from 1997 to 2014 were eligible for inclusion. All patients were treated with induction chemotherapy (chemo) with surgery followed by myeloablative chemo & stem cell rescue. Primary & metastatic site (MS) RT were applied according to institutional protocol. CT & I-123 MIBG scans were used to assess Curie scores at diagnosis, post-induction, post-transplant & failure. Overall (OS), & progression-free survival (PFS) were described using the Kaplan-Meier estimator. Cox proportional hazards frailty (cphfR) & CPH regression (CPHr) were used to identify covariates predictive of MSF & new site MSF. Results: Forty-two (55%) patients had documented MSFs. Consolidative MS RT was applied to 30 MSs in 10 patients. Original site MSF occurred in 146 of 383 (38%) & 18 of 30 (60%) non-irradiated & radiated MSs respectively. Original site MSF occurred in post-induction MIBG avid lesions in 68 of 81 (84%) & 12 of 14 (85%) non-irradiated & radiated MSs respectively. The median OS & PFS were 61 mo (95% CI 42.6-NR) & 24.1 mo (95% CI 16.5-38.7). Univariate cphfR identified an increased hazard for original MSF when MIBG avid following induction chemo (HR 4.9, 95%CI 1.1-20.9, p = 0.03) & transplant (HR 7.3 95%CI 1.8-30.2, p = 0.006) relative to lesions that cleared after induction. Notably, MS RT nor site location did not modify the hazard for MSF. Multivariate CPHr identified inability to undergo transplant (HR 32.4 95%CI 9.3-96.8, p < 0.001) &/or maintenance chemo (HR 5.2, 95%CI 1.7-16.2, p = 0.005) & the presence of lung metastases (HR 4.4 95%CI 1.7-11.1, p = 0.002) at diagnosis as predictors of new site MSF. The new MSF free survival at 3 years was 25% vs. 87% in patients with high-risk factors relative to those without the risk factors suggesting limited benefit of consolidative MS RT in this population. Conclusions: Metastatic lesions that remained MIBG avid following induction chemo & post-transplant had an increased hazard for MSF. Consolidative site RT likely has limited benefit in patients with HR features.