Patterns of Failure in High-Risk Neuroblastoma with or Without Metastatic Site Irradiation

Purpose/Objective(s) Neuroblastoma is the most common extracranial malignancy diagnosed in childhood. Despite recent improvements in outcomes and an overall 5-year survival of >80%, the majority of children with high-risk neuroblastoma will relapse despite aggressive treatment. As part of their treatment paradigm, radiation treatment (RT) is recommended to the primary site after surgery, as well as to metastatic sites of disease that continue to be metaiodobenzylguanidine (MIBG)-avid post-induction chemotherapy. While there is an abundance of data supporting the former, data is limited on the role of RT to metastatic sites and thus our practice has generally been to withhold RT to metastatic sites. The aim of this study is to examine patterns of failure in patients with high-risk metastatic neuroblastoma to better determine the value of metastatic site RT. Materials/Methods We performed an IRB-approved retrospective review from our institutional database of patients with high-risk neuroblastoma who were treated from 2010-2020. The included patients had MIBG-avid metastatic disease at the time of diagnosis, as well as first relapse. These patients achieved a partial or complete response before first relapse, and did not receive total body radiation or therapy with 131I-MIBG prior to first relapse. We analyzed the patients who failed and compared the anatomical location of all sites at initial relapse to sites that were MIBG-avid on post-induction chemotherapy scan. Results With a median follow up of 38 months, 13 of the 41 patients (32%) treated during this time recurred, and 5 (12%) died. 3 patients who recurred were excluded from the analysis as they did not have sufficient records. Of the 10 patients analyzed with recurrent disease, there were 70 MIBG-avid metastatic sites on post-induction chemotherapy scan, and of these only 11 (16%) received RT. There were 13 total MIBG-avid metastatic sites at time of first recurrence, of which 6 (46%) were in original site present on post-induction chemo MIBG scan, 1 which received radiation treatment and the other 5 (38%) did not. Of the sites that did receive radiation treatment, 10/11 (91%) did not recur. In analysis per patient, 4/10 (40%) recurred initially in metastatic sites that were MIBG-avid on post-induction scan, while the remaining majority recurred in both initial and new sites or new sites only. Conclusion In this unique cohort of high-risk neuroblastoma patients who mostly did not receive RT to post-induction chemotherapy MIGB-avid metastatic sites, a little less than half of the patients and sites relapsed in initial areas, while the remaining relapsed at new sites. Those sites that were treated with RT had excellent local control >90%, consistent with prior reports. While this data suggests that RT to metastatic sites on post-induction chemotherapy MIBG scan may improve outcomes, the sample size is limited and caution must be taken to balance potential benefits with risks, especially in situations with several metastatic sites.