title: MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.
abstract: BACKGROUND
  Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma.
  
  
  METHODS
  Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961. Comparisons of clinical and biologic features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free (EFS) and overall (OS) survival compared using log-rank tests and modeled using Cox models.
  
  
  RESULTS
  Thirty of 343 patients (8.7%) had MIBG nonavid disease. Patients with nonavid tumors were less likely to have adrenal primary tumors (34.5 vs. 57.2%; P = 0.019), bone metastases (36.7 vs. 61.7%; P = 0.008), or positive urine catecholamines (66.7 vs. 91.0%; P < 0.001) compared with patients with MIBG avid tumors. Nonavid tumors were more likely to be MYCN amplified (53.8 vs. 32.6%; P = 0.030) and had lower norepinephrine transporter expression. Patients with MIBG nonavid disease had a 5-year EFS of 50.0% compared with 38.7% for patients with MIBG avid disease (P = 0.028). On 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 = 0.034).
  
  
  CONCLUSIONS
  Patients with MIBG nonavid neuroblastoma have lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN-amplified tumors, these patients have superior outcomes compared with patients with MIBG avid disease.
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.affiliation: CS Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan.
authors.forename: Rajen
authors.initials: R
authors.lastname: Mody
authors.affiliation: Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida.
authors.forename: Arlene
authors.initials: A
authors.lastname: Naranjo
authors.affiliation: Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida.
authors.forename: Collin
authors.initials: C
authors.lastname: Van Ryn
authors.affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Douglas
authors.initials: D
authors.lastname: Russ
authors.affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Derek
authors.initials: D
authors.lastname: Oldridge
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Susan
authors.initials: S
authors.lastname: Kreissman
authors.affiliation: Princess Margaret Hospital for Children, Perth, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Baker
authors.affiliation: Seattle Children's Hospital, University of Washington, Seattle, Washington.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Parisi
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Shulkin
authors.affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Harrison
authors.initials: H
authors.lastname: Bai
authors.affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Diskin
authors.affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Vandana
authors.initials: V
authors.lastname: Batra
authors.affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.affiliation: Seattle Children's Hospital, University of Washington, Seattle, Washington.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Park
authors.affiliation: UCSF Benioff Children's Hospital and University of California, San Francisco School of Medicine, San Francisco, California.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.affiliation: CS Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan.
authors.forename: Gregory
authors.initials: G
authors.lastname: Yanik
mesh_terms: D019797:3-Iodobenzylguanidine / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine
keywords: MIBG; MYCN; avidity; neuroblastoma; norepinephrine transporter