Outcomes After Definitive Radiation Treatment of Metastatic Sites in Patients With Stage IV Neuroblastoma

Abstract

Purpose/Objective(s): In patients (pts) with high-risk metastatic neuroblastoma (NB), the benefit of radiation therapy (RT) to metastatic sites (MS) as part of primary treatment has not been fully investigated. The purpose of this study was to characterize the distribution of MS, pattern of RT for MS, and evaluate patterns of recurrence and outcomes in this patient population. Materials/Methods: The records of all pts diagnosed with stage IV NB (International NB Staging System) between 8/2000 and 1/2010 at Children’s Healthcare of Atlanta were reviewed. Exclusion criteria included: bone-marrow-only MS, total body irradiation, or no imaging follow-up. A total of 37 pts met eligibility. Image-defined MS involvement was documented at the following time points: pre-induction (preI) chemotherapy (CTX), post-induction (postI) CTX, and post-transplant/pre-RT (preRT). MS involvement was further classified into 4 categories based on location: appendicular skeleton, axial skeleton, calvarium, and soft tissue. The median follow-up period for pts without relapse was 61 months (range, 9-113 months). Actuarial rates were determined by the Kaplan-Meier method from start of induction CTX. Time-to-event rates were compared using the log-rank test. Results: The median age at diagnosis was 3.7 years (range, 0.7-20.7). Extent of resection was gross total, subtotal, and biopsy only in 26 pts (70%), 9 pts (24%), and 2 pts (5%), respectively. Five-year (yr) overall survival (OS) for all pts was 67%. All pts received RT to their primary site and regional lymph nodes. The 5-yr local control rate of the primary site was 94%. Thirteen pts (35%) received upfront RT to one MS category: 2 pts (appendicular), 4 pts (axial), 3 pts (calvarium), and 4 pts (soft tissue). The median RT dose to MS was 21.6 Gy (range, 21.0-30.6) at 1.8 Gy/ fraction. Among these pts (n Z 13), infield recurrence occurred in 4 pts (31%), and out-of-field recurrence occurred in 5 pts (38%). There was no difference in 5-yr OS between pts who were treated with or without RT to a MS (73% vs 63%, pZ NS). For pts who had positive MS after induction CTX vs those without, there was no difference in 5-yr OS (64% vs 68%, p Z NS) or 5-yr MS control (56% vs 69%, p Z NS). Of the 78 preI CTX involved MS locations, 71% became negative on postI CTX imaging. Of the 70 negative MS locations on preI CTX imaging, only 3% became positive on postI CTX imaging. Ten pts had preRT imaging, and of the 11 postI CTX positive MS locations, 3 became negative on preRT imaging. Conclusions: Treatment of MS with RT as part of definitive therapy in stage IV NB was not associated with improved OS or MS control. Infield recurrences after RT to MS are substantial, and RT dose may need to be evaluated. The presence of residual MS after induction CTX did not predict poorer survival. Further studies are necessary to clarify the role of RT to MS in the definitive setting. Author Disclosure: S. Kandula: None. R.S. Prabhu: None. H. Katzenstein: None. M. Qayed: None. N. Esiashvili: None.