Status: Funded - Closed
Incidence and risk for secondary malignancy in neuroblastoma patients after treatment with 131I-MIBG
Kelly Huibregtse, M.S., M.D.
BACKGROUND: 131I- metaiodobenzylguanidine (131I-MIBG) is a radiopharmaceutical that delivers intravenous targeted radiotherapy that is effective in children with refractory and disseminated neuroblastoma. However, there have been several case reports of new secondary cancers and leukemia occurring after this therapy.
GAP: To date, the incidence and characteristics of secondary malignancy after 131I-MIBG are not well characterized.
HYPOTHESIS: We hypothesized that there was an increased risk of secondary malignancy in patients with neuroblastoma treated with 131I-MIBG compared to other patients with high-risk neuroblastoma who did not receive 131I-MIBG or other high-risk solid tumor patients.
METHODS: The primary aim of this study was to determine the incidence and characteristics of secondary malignancy in a large, multi-institutional cohort of patients with neuroblastoma treated with 131I-MIBG. We conducted a multi-institutional retrospective chart review of patients less than 22 years of age with neuroblastoma treated with 131I-MIBG therapy to characterize the incidence of secondary malignancy in this population. A competing risks approach was used to calculate the cumulative incidence of SMN from time of first exposure to 131I-MIBG. A competing risks regression was used to identify potential risk factors for SMN.
RESULTS: The analytical cohort included 644 patients treated with 131I-MIBG. The cumulative incidence of SMN was 7.6% (95% CI 4.4-13.0%) and 14.3% (95% CI 8.3-23.9%) at five and ten years from first 131I-MIBG, respectively. No increase in SMN risk was found with increased number of 131I-MIBG treatments or higher cumulative activity per kilogram of 131I-MIBG received (p=0.72 and p=0.84, respectively). Thirteen of the 19 reported SMN were hematologic. In a multivariate analysis controlling for variables with p<0.1 (stage, age at first 131I-MIBG, bone disease, disease status at time of first 131I-MIBG), patients with relapsed/progressive disease had significantly lower risk of SMN (Subdistribution Hazard Ratio 0.3, 95% CI, 0.1-0.8, p=0.023) compared to patients with persistent/refractory neuroblastoma.
IMPACT: A major aim of this project was to guide screening decisions in this patient population. Our hope is that a better understanding of the risk of second malignancy after receiving 131I-MIBG therapy will improve patient survival as well as quality of life.
University of California, San Francisco
California, Pennsylvania, California, Massachusetts, Michigan, Ohio