Oral Presentation Advances in Neuroblastoma Research Congress 2016

Clinical, biologic, and outcome differences according to MIBG avidity in children with neuroblastoma: A report from the Children’s Oncology Group (COG) (#57)

Steven G. DuBois 1 , Rajen Mody 2 , Collin Van Ryn 3 , Arlene Naranjo 3 , Susan Kreissman 4 , David L. Baker 5 , Marguerite Parisi 6 , Barry Shulkin 7 , John M. Maris 8 , Vandana Batra 8 , Julie R. Park 6 , Katherine K. Matthay 9 , Gregory Yanik 2
  1. Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston
  2. University of Michigan, Ann Arbor
  3. University of Florida, Gainesville
  4. Duke University, Durham
  5. Princess Margaret Hospital for Children, Perth
  6. Seattle Children's Hospital, Seattle
  7. St. Jude Children's Research Hospital, Memphis
  8. Children's Hospital of Philadelphia, Philadelphia
  9. UCSF School of Medicine, San Francisco

Background: Prior investigations suggest that neuroblastomas (NBL) that do not accumulate MIBG (MIBG non-avid) may have more favorable features compared to MIBG avid tumors. We compared clinical/biologic features and clinical outcomes between patients with MIBG non-avid vs. avid NBL.

 

Methods: A retrospective analysis was performed of patients with metastatic high- or intermediate-risk NBL treated on COG protocols A3973 or A3961, respectively. A3973 patients had baseline MIBG scans centrally reviewed (n=306). A3961 patients with bone metastasis at baseline were included (n=37). Comparisons of clinical/biological features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free survival (EFS) was compared using log-rank tests and modeled using Cox models.

 

Results: Thirty of 343 patients (8.7%) in the analytic cohort had MIBG non-avid NBL (n=1 from A3961 and n=29 from A3973). Non-avid tumors were less likely to be adrenal primary tumors (34.5% vs. 57.2%; p = 0.02) or have bone metastases (36.7% vs. 61.7%; p = 0.008) and were more likely MYCN amplified (53.8% vs. 32.6%; p = 0.03). The rate of positivity for urine catecholamine levels (available from A3973 only) was lower in patients with non-avid NBL (66.7% vs. 91%; p < 0.001). Patients with MIBG non-avid NBL had a 5-year EFS of 50.0% compared to 38.7% for patients with MIBG avid NBL (p = 0.03). On backward-selected multivariate testing in high-risk patients, MIBG avidity was the sole adverse prognostic factor for EFS identified (hazard ratio 1.77; 95% confidence interval 1.04 – 2.99; p = 0.03); MYCN status, age, grade, MKI, and ploidy were not prognostic.

 

Conclusions: MIBG non-avid NBL represents a distinct clinical subgroup with lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN amplified tumors, patients with MIBG non-avid NBL have superior outcomes compared to patients with MIBG avid NBL.