107 Impact of Post-Induction Curie Scores in High-Risk Neuroblastoma

Track: BMT Tandem "Scientific" Meeting
Friday, February 13, 2015, 10:30 AM-12:00 PM
Seaport Ballroom DE (Manchester Grand Hyatt)
Gregory Yanik, MD , Pediatric Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Arlene Naranjo, PhD , Childrens Oncology Group, Gainesville, FL
Marguerite T. Parisi, MD , Seattle Childrens Hospital, Seattle, WA
Barry L. Shulkin, MD , St. Jude Research Childrens Research Center, Memphis, TN
Helen Nadel, MD , British Columbia Childrens Hospital, Vancouver, BC, Canada
Michael J Gelfand, MD , Cincinnati Childrens Hosptial Medical Center, Cincinnati, OH
Ruth Ladenstein, MD , BMT Unit, St. Anna Children's Hospital, Vienna, Austria
Ariane Boubaker, MD , Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Ulrike Poetschger, PhD , St. Anna Children's Cancer Research Institute, Wien, Austria
Dominique Valteau-Couanet, MD , Institut Gustave-Roussy, Villejuif, France
Susan G Kreissman, MD , Duke University, Durham, NC
Julie R Park, MD , Seattle Children's Hospital, Seattle, WA
Katherine K Matthay, MD , UCSF Medical Center, San Francisco, CA
Audio File Recorded Presentation
BACKGROUND: Myelo-ablative chemotherapy with autologous stem cell rescue, local radiotherapy and chimeric antibody are routinely given post-induction in the management of high risk neuroblastoma (NBL). The Children’s Oncology Group (COG) recently reported the prognostic impact of a semi-quantitative MIBG-based scoring method, termed Curie scoring (CS) in high risk disease.  In particular, post-induction (pre-transplant) CS >2 were associated with poor event-free (EFS) and overall survival (OS). We now validate the impact of Curie scoring in an independent data set, the SIOPEN-HR-NBL1 (SIOP-NB) study.

METHODS: MIBG scans from patients with MIBG avid, INSS stage 4 neuroblastoma enrolled on SIOP-NB were evaluated post-induction (n=330), prior to transplant.  Scans were evaluated in 10 different anatomic regions by 2 reviewers, including 9 skeletal segments and 1 soft issue region. Each region was scored 0-3 based upon disease extent, and a cumulative consensus score generated. Optimal cut-points from post-induction scans were determined using the Youden index, with EFS and OS determined. Post-induction CS from patients enrolled on COG A3973 (n= 237) were used for comparison. Patients received busulfan-melphalan (BuMel) in SIOP-NB, and carboplatin-etoposide-melpahlan (CEM) in COG A3973, as transplant conditioning.  

RESULTS: The optimal CS cut-point post-induction (pre-transplant) was 2 in both SIOP-NB and COG A3973, with a post-induction CS >2 associated with inferior outcomes in each study. In SIOP-NB, 5-year EFS were 39.2±4.7% vs 16.4±4.2% for patients with post-induction CS ≤2 vs >2 (p<0.001). In comparison, 5-year EFS were 42%±5.8% vs 10.5%±10.0% (p<0.001) for patients with post-induction CS ≤2 vs > 2 in COG A3973. A post-induction CS >2 carried prognostic significance for both MYCN amplified and MYCN non-amplified tumors, in both SIOP-NB and COG A3973. In particular, post-induction CS > 2 were associated with extremely poor outcomes for patients with MYCN amplified disease, with a 5-year EFS 13.8%±12% in SIOP-NB. The post-induction CS maintained independent statistical significance in Cox models when compared to standard predictive covariates age and MYCN in both trials.

CONCLUSION: The prognostic significance of post-induction CS has now been validated in an independent cohort of patients, with a post-induction CS >2 associated with inferior outcome in two large cooperative group trials, SIOPEN-HR-NBL1 and COG A3973. MIBG scoring should be incorporated into pre-transplant evaluations in high risk NBL, and patients with CS >2 considered for alternative regimen.

Disclosures:
Nothing To Disclose
See more of: Oral Abstracts - Session H - Pediatric Disorders & Late Effects/Quality of Life
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