Poster Presentation Advances in Neuroblastoma Research Congress 2016

High-risk neuroblastoma without MYCN amplification in patients between 12 and 18 months: Is there a hidden low-risk patient group? (#271)

Inge M. Ambros 1 , Gudrun Schleiermacher 2 , Valérie Combaret 3 , Raffaella Defferrari 4 , Katia Mazzocco 4 , Rosa Noguera 5 , Luigi Varesio 6 , Marta Jeison 7 , Nadine van Roy 8 , Nick Bown 9 , David Betts 10 , Gunhild Trøen 11 , Klaus Beiske 11 , Roberto Luksch 12 , Adela Canete 13 , Isaac Yaniv 14 , Vassilios Papadakis 15 , Walentyna Balwierz 16 , Cormac Owens 10 , Ulrike Pötschger 1 , Deborah Tweddle 17 , Claudia Pasqualini 18 , Dominique Valteau-Couanet 18 , Fikret Rifatbegovic 1 , Ruth Ladenstein 1 19 , Peter F. Ambros 1 19
  1. CCRI, Children's Cancer Research Institute, Vienna, Austria
  2. Département d'Oncologie Pédiatrique et INSERM U830, Institut Curie, Paris, France
  3. Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France
  4. Dipartimento Ricerca Traslazionale, U.O.C. Anatomia Patologica, Genova, Italy
  5. Department of Pathology, Medical School of Valencia, Valencia, Spain
  6. Dipartimento Ricerca Traslazionale, Medicina di Laboratorio, Diagnostica e Servizi, IRCCS Istituto Giannina Gaslini, Genova, Italy
  7. The Rina Zaizov Pediatric Hematology Oncology Dept., Schneider Children's Medical Center of Israel, Petah Tikva, Israel
  8. Center for Medical Genetics, Cancer Research Institute Ghent, Ghent, Belgium
  9. Northern Genetics Service, Institute of Genetic Medicine, Newcastle upon Tyne, UK
  10. Our Lady's Children's Hospital, Dublin, Ireland
  11. Department of Pathology, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  12. Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, Milan, Italy
  13. J. Sección Oncología Pediátrica., Hospital Universitario y Politécnico La Fe., Valencia, Spain
  14. Schneider Children‘s Medical Center of Israel, Petah Tikva, Israel
  15. Agia Sofia Children’s Hospital Athens, Athens, Greece
  16. Jagiellonian University Medical College, Krakow, Poland
  17. Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle upon Tyne, UK
  18. Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy Cancer Campus, Villejuif, France
  19. Department of Pediatrics, Medical University of Vienna, Vienna, Austria

Background: The HR-NBL-1/SIOPEN trial accrues stage M neuroblastoma patients ≥ 12 months at diagnosis, irrespective of MYCN amplification (MNA) status. The International Neuroblastoma Risk Grouping (INRG) has established a cut-off age of ≤18m for low-risk metastatic neuroblastoma (stage Ms) given clinical and genomic criteria (no MNA, no 11q-) are met. The aim of this SIOPEN Biology committee analysis is to genomically identify possible stage Ms patients in the 12-18m HR-NBL1/SIOPEN study.

Methods: Information on segmental chromosome aberrations (SCA) and ploidy was available for 36 patients aged 12-18m (no-MNA tumors). NB samples were analyzed by FISH and/or multi-locus/pangenomic techniques (MLPA/array-CGH/SNP-arrays). Genomic data were centrally reviewed by the SIOPEN Biology members and SCAs subdivided into typical (typSCAs: 1p/3p/4p/11q losses; 1q/2p/17q gains) and atypical ones (atypSCAs). Ploidy was determined by FCM/ICM or by evaluation of numeric aberrations (near-diploid vs. aneuploid).

Results: Five of 7 patients without skeletal metastases had no 11q-. One died after relapse (incomplete genomic data); another one died on treatment. The other three remaining patients had no relapse; their tumors showed aneuploidy without SCAs (for one of them there is no atypSCA information).

Altogether, typSCAs occurred in 33/36 tumors (80% 17q gain, 69% 11q loss), atypSCAs in 17/22.
Near-diploid tumors (n=22) showed 1-6 typSCA, aneuploid neuroblastomas (n=12) 0-3 typSCAs (two typSCA tumors without ploidy information). Of 16 patients without or with up to 2 typSCAs (10 aneuploid), one patient relapsed, 2 died of NRM (non-relapse mortality; altogether 5/36 patients with NRM) but none died of disease. However, of 16 patients with >2 typSCA (1 aneuploid), 4 relapsed, 2 are DOD and 3 had NRM. 3/9 patients with 1p- tumors relapsed and died (plus 3 NRM), whereas 0/24 patients without 1p- died of disease, despite 3 relapses (2 NRM). 2/4 tumors with +1q relapsed.

Conclusion: In the 12-18m age group, a small number of stage M patients without skeletal metastases and with favorable genomic features could represent stage Ms patients.