Anatomic Patterns of Relapse and Progression Following Treatment With 131I-MIBG in Metastatic Neuroblastoma

Abstract

Neuroblastoma is the most common pediatric extracranial solid tumor. Patients with MIBG-avid relapsed or refractory neuroblastoma after up front therapy may exhibit significant, but often transient, responses to salvage treatment with 131I-MIBG. It is not known whether disease progression following 131I-MIBG treatment occurs in previously involved versus new anatomic sites of disease. Understanding this pattern of relapse may inform the use of consolidative external beam radiation therapy following 131I-MIBG administration. Patients with relapsed or refractory metastatic MIBG-avid neuroblastoma or ganglioneuroblastoma who received single-agent 131I-MIBG on phase 2 and compassionate access protocols at a single-institution were included if they had 1) stable or responding disease 6-8 weeks following 131I-MIBG infusion, but subsequently experienced disease progression and 2) had serial diagnostic MIBG scans available from protocol enrollment through first progression. Scans were reviewed to establish anatomic locations and temporal evolution of MIBG-avid disease. Progression was defined as development of MIBG-avid disease in a previously uninvolved anatomic location, or as recurrence of MIBG avidity in a previously involved site that had fully cleared following MIBG treatment. A total of 142 MIBG-avid metastatic sites were identified immediately prior to MIBG therapy in a cohort of 15 patients (seven male, eight female). Median age at first 131I-MIBG treatment was 9.6 years (range, 4.3-51.2). Following first 131I-MIBG infusion, and prior to disease progression, five patients received additional 131I-MIBG treatments, but none received external beam radiation therapy. Median time to progression after first 131I-MIBG treatment was 0.6 years (range, 0.2-2.5). At first progression, a total of 140 MIBG-avid sites were identified, of which 103 (74%) overlapped with pretreatment disease sites, while 37 (26%) represented anatomically new disease areas. Nine of 15 patients had one or more new MIBG avid site at first progression. Of the 103 involved sites at progression that overlapped with pretreatment disease, 19 represented relapsed sites that had cleared following MIBG therapy, 19 were persistent but increasingly MIBG-avid, and 65 were stably persistent. Previously involved anatomic disease sites predominate at disease progression following 131I-MIBG treatment; nevertheless, the majority of patients progressed in at least one new anatomic disease site. This observation suggests that consolidative focal therapies targeting residual disease sites may be of limited benefit in preventing systemic disease progression following 131I-MIBG treatment of relapsed or refractory neuroblastoma.