Oral Presentation Advances in Neuroblastoma Research Congress 2016

Incidence and risk factors for secondary malignancy in patients with neuroblastoma after treatment with 131I-metaiodobenzylguanidine (#122)

Kelly Huibregtse 1 , Kieuhoa Vo 1 , Steven Dubois 2 , Stephani Fetzko 3 , Vandana Batra 4 , John Maris 4 , Araz Marachelian 5 , John Neuhaus 1 , Brian Weiss 6 , Greg Yanik 7 , Katherine Matthay 1
  1. University of California San Francisco, San Francisco, CA, United States
  2. Dana-Farber / Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA
  3. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
  4. Department of Pediatric Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  5. Department of Pediatric Oncology, Children's Hospital of Los Angeles, Los Angeles, CA, USA
  6. Department of Pediatric Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
  7. University of Michigan Medical Center, Ann Arbor, MI, USA

Intro: 131I-MIBG is a highly active form of tumor-targeted radiotherapy in patients with relapsed neuroblastoma, with response rates of 30% to 40%. Several reports of second malignant neoplasm (SMN) in patients after treatment with 131I-MIBG suggest the possibility of increased risk of secondary malignancy, particularly myelodysplasia and leukemia. Incidence of and risk factors for SMN after 131I-MIBG have not been defined.

 

Methods: This is a multi-institutional retrospective review of patients with neuroblastoma treated with 131I-MIBG therapy at four institutions between March 1, 1984 and March 1, 2014. A competing risks approach was used to calculate the cumulative incidence of SMN from time of first exposure to 131I-MIBG. Competing risks regression was used to identify potential risk factors for secondary malignancy.

 

Results: The analytical cohort included 644 patients treated with 131I-MIBG. The cumulative incidence of SMN was 7.6% (90% CI 4.8-11.9%) and 14.3% (90% CI 9.1-22.1%) 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. An increased risk of SMN was found in patients who had bone disease at the time of first 131I-MIBG therapy. In a multivariate analysis, 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.

 

Conclusion: The cumulative risk of SMN after 131I-MIBG therapy for patients with relapsed or refractory neuroblastoma is similar to the published incidence for high-risk neuroblastoma overall. We found no dose-dependent increase in SMN risk. As the number of patients treated with 131I-MIBG earlier after diagnosis, and length of follow up time from 131I-MIBG therapy increase, it will be important to reassess this risk.