title: Incidence and risk factors for secondary malignancy in patients with neuroblastoma after treatment with (131)I-metaiodobenzylguanidine.
abstract: Several reports of second malignant neoplasm (SMN) in patients with relapsed neuroblastoma after treatment with (131)I-MIBG suggest the possibility of increased risk. Incidence of and risk factors for SMN after (131)I-MIBG have not been defined. This is a multi-institutional retrospective review of patients with neuroblastoma treated with (131)I-MIBG therapy. A competing risk approach was used to calculate the cumulative incidence of SMN from time of first exposure to (131)I-MIBG. A competing risk regression was used to identify potential risk factors for SMN. The analytical cohort included 644 patients treated with (131)I-MIBG. The cumulative incidence of SMN was 7.6% (95% confidence interval [CI], 4.4-13.0%) and 14.3% (95% CI, 8.3-23.9%) at 5 and 10 years from first (131)I-MIBG, respectively. No increase in SMN risk was found with increased number of (131)I-MIBG treatments or higher cumulative activity per kilogram of (131)I-MIBG received (p = 0.72 and p = 0.84, respectively). Thirteen of the 19 reported SMN were haematologic. In a multivariate analysis controlling for variables with p < 0.1 (stage, age at first (131)I-MIBG, bone disease, disease status at time of first (131)I-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. The cumulative risk of SMN after (131)I-MIBG therapy for patients with relapsed or refractory neuroblastoma is similar to the greatest published incidence for high-risk neuroblastoma after myeloablative therapy, with no dose-dependent increase. As the number of patients treated and length of follow-up time increase, it will be important to reassess this risk.
authors: University of California San Francisco Benioff Children's Hospital, USA. Electronic address: kelly.huibregtse@ucsf.edu.
authors: Kelly E
authors: KE
authors: Huibregtse
authors: Department of Pediatrics, University of California San Francisco Benioff Children's Hospital, USA. Electronic address: Kieuhoa.Vo@ucsf.edu.
authors: Kieuhoa T
authors: KT
authors: Vo
authors: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, USA. Electronic address: Steven_Dubois@dfci.harvard.edu.
authors: Steven G
authors: SG
authors: DuBois
authors: Department of Pediatrics, Baylor University Medical Center, USA. Electronic address: fetzko@bcm.edu.
authors: Stephanie
authors: S
authors: Fetzko
authors: University of California San Francisco Benioff Children's Hospital, Department of Biostatistics, USA. Electronic address: John.Neuhaus@ucsf.edu.
authors: John
authors: J
authors: Neuhaus
authors: Children's Hospital of Philadelphia, Department of Pediatric Oncology, USA. Electronic address: Batrav@email.chop.edu.
authors: Vandana
authors: V
authors: Batra
authors: Children's Hospital of Philadelphia, Department of Pediatric Oncology, USA. Electronic address: Maris@email.chop.edu.
authors: John M
authors: JM
authors: Maris
authors: Cincinnati Children's Hospital Medical Center, Division of Pediatric Oncology, USA. Electronic address: Brian.Weiss@cchmc.org.
authors: Brian
authors: B
authors: Weiss
authors: Children's Hospital of Los Angeles, New Approaches to Neuroblastoma Research, USA. Electronic address: AMarachelian@chla.usc.edu.
authors: Araz
authors: A
authors: Marachelian
authors: Department of Pediatrics, University of Michigan Medical Center, USA. Electronic address: gyanik@med.umich.edu.
authors: Greg A
authors: GA
authors: Yanik
authors: Department of Pediatrics, University of California San Francisco Benioff Children's Hospital, USA. Electronic address: kate.matthay@ucsf.edu.
authors: Katherine K
authors: KK
authors: Matthay
mesh_terms: D019797:3-Iodobenzylguanidine / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D019337:Hematologic Neoplasms / Q000139:chemically induced; D006801:Humans; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D016609:Neoplasms, Second Primary / Q000139:chemically induced*; D009447:Neuroblastoma / Q000188:drug therapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects*; D012189:Retrospective Studies; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine
keywords: Cancer; Chemotherapy; I-metaiodobenzylguanidine; MIBG; Neuroblastoma; Paediatrics; SMN; Second malignancy; Solid tumour; Survivorship