Poster Presentation Advances in Neuroblastoma Research Congress 2016

Survival and prognostic factors for children 12 to 18 months of age with stage 4 non-MYCN amplified neuroblastoma treated in the SIOPEN high-risk trial (#168)

Claudia Pasqualini 1 , Ulrike Pötschger 2 , Peter F. Ambros 2 , Shifra Ash 3 , Daniel Morgenstern 4 , Andrea Di Cataldo 5 , Adela Cañete 6 , Maria Corrias 7 , Pablo Berlanga 6 , Maria Rita Castellani 8 , Lorenzo Biassoni 4 , Julia Balaguer 6 , Martin Kropf 9 , Günter Schreier 9 , Gudrun Schleiermacher 10 , Dominique Valteau-Couanet 1 , Ruth Ladenstein 2
  1. Gustave Roussy, Villejuif Cedex , France
  2. Children’s Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna , Austria
  3. Schneider Children's Medical Center of Israel , Israel
  4. Great Ormond Street Hospital for Children NHS Foundation Trust, London
  5. Azienda Policlinico-OVE , Catania
  6. La Fe Hospital, Valencia
  7. IRCCS Istituto Giannina Gaslini, Genova
  8. Istituto Nazionale dei Tumori , Milano
  9. AIT Austrian Institute of Technology, Graz
  10. Institut Curie, Paris

Background. Better outcome has been described in children 12-18 months old with stage 4 non-MYCN amplified (nonMNA) neuroblastoma. Our aim was to analyze the clinical and biological data at diagnosis in this cohort, and their impact on outcome.

Subjects and methods. Children 366-547 days old with stage 4 nonMNA neuroblastoma treated in the high-risk neuroblastoma (HR-NBL)/SIOPEN trial were included. Treatment consisted of induction chemotherapy (COJEC) with high-dose chemotherapy (HDC) and maintenance treatment. The amended HR-NBL1/SIOPEN(V1.5) trial excluded patients with only numerical chromosomal alterations (NCAs) from HDC. Central review of MIBG scans was performed by two independent reviewers. Kaplan-Meier estimator and estimates of cumulative incidences were compared with log-rank test and Gray test.

Results. Eighty-four patients met the inclusion criteria. Median age was 448 days (range: 366-540d). Bone marrow and bone involvement were detected in 60/84 and 54/84 patients, respectively; liver and lung disease in 12/84 and 10/84 patients. The median follow-up was 5.9 years (1.06-12.5yrs). Five-year event-free survival (EFS) and overall survival (OS) were 60%±6% and 70%±6%, respectively. Five-year recurrence rate was 27%±5%. Time to recurrence was 32.1 months (3.3-54.8mo). Five treatment-related deaths occurred: 3 with HDC (2 infections after Busulfan-Melphalan, 1 multi-organ-failure after Carboplatin-Etoposide-Melphalan) and 2 with surgery. Five-year EFS was better in children with LDH (p=0.01) and ferritin levels < 2xULN (p=0.01), and no lung disease (p<0.0001). In these patients, 5-year EFS was still less than 70%. Segmental chromosomal alterations (SCAs) were detected in 33/36 patients, and 1p loss (p=0.06) and 1q gain (p=0.008) were associated to worse prognosis. The remaining 3/36 patients had no SCAs: 2/3 received HDC, and all of them were alive at the last follow-up.

Conclusion. Prognosis of children 12-18 months old with stage 4 nonMNA neuroblastoma needs to be further improved. NRM remains a major concern in this population.