Poster Presentation Advances in Neuroblastoma Research Congress 2016

Genomic profiling in low and intermediate risk neuroblastoma to refine treatment stratification and improve patient outcome – LINES: a SIOPEN Trial (#300)

Gudrun Schleiermacher 1 , Raffaella Defferrarri 2 , Katia Mazzocco 2 , Inge Ambros 3 , Nathalie Auger 4 , Smadar Avigad 5 , Klaus Beiske 6 , Nathalie Clement 1 , Valérie Combaret 7 , Jaime Font De Mora 8 , Marta Jeison 5 , Tommy Martinsson 9 , Annick Muhlethaler 10 , Rosa Noguera 11 , Gaelle Pierron 1 , Maria Rossing 12 , Nadine Van Roy 13 , Luigi Varesio 14 , Jean Michon 1 , Véronique Mosseri 1 , José D Bermudez 11 , Adela Cañete 8 , Andrea di Cataldo 15 , Vassilios Papadakis 16 , Kate Wheeler 17 , Peter Ambros 3
  1. Institut Curie, Paris, France
  2. IRCCS Istituto Giannina Gaslini, Genoa, Italy
  3. Children's Cancer Research Institute, Vienna, Austria
  4. Gustave Roussy, Villejuif, France
  5. Schneider Children's Medical Center of Israel, Petach Tikvah, Israel
  6. Oslo University Hospital Radiumhospitalet, Oslo, Norway
  7. Centre Léon Bérard, Lyon, France
  8. La Fe Hospital Research Institute, Valencia, Spain
  9. Gotheburg University, Gotheburg, Sweden
  10. University Hospital CHUV, Lausanne, Switzerland
  11. University of Valencia, Valencia, Spain
  12. Rigshopitalet, Copenhagen, Denmark
  13. Ghent University, Ghent, Belgium
  14. I. Gaslini, Genoa, Italy
  15. University of Catania, Catania, Italy
  16. Aghia Sophia Children's Hospital, Athens, Greece
  17. Oxford University Hospital, Oxford, United Kingdom

Background: In neuroblastoma (NB), a genomic profile characterized by segmental chromosome alterations is associated with poorer outcome. The SIOPEN LINES trial (Low and Intermediate Neuroblastoma European Study) was designed to maintain or improve the excellent outcome in low risk patients (LR), whilst diminishing overall treatment burden whenever possible. Treatment is stratified according to the genomic profile in addition to clinical parameters. In intermediate risk (IR) patients, the genomic profile is studied prospectively.

 

Methods: NB samples with >60% tumor cells are analyzed using pangenomic techniques, with central review, entering of data in the SIOPEN-R-NET database, and return of the clinically relevant conclusions to the treating clinician within six weeks after diagnosis. NB without MYCN amplification are classified into two groups: numerical chromosome alterations (NCA) only, versus segmental chromosome alterations (SCA) >2Mb known to occur recurrently in NB, without or with numerical alterations.

 

Results: For 277 enrolled patients (190 LR, 87 IR), genomic profiling was performed in 230 cases using MLPA (n=7), aCGH (n=151), SNP-arrays (n=61) or other techniques (n=11). A genomic profile could be determined in 203 cases (131 NCA, 72 SCA). In 27 cases, no result was obtained, either because no copy number changes were seen (n=7), or because of alterations for which the prognostic relevance has not been clearly established (n=10), including small interstitial deletions of chromosomes 8p or 3p, deletions of 5q, 11p, 17p, 19q and 22q, 2 cases with focal amplification of 12q14 encompassing CDK4/MDM2, amplification of 1p34.2, or a gain of 18p. For 10 other cases, no genomic profile could be obtained either due to insufficient material or technical issues. For 47 cases (23 LR, 24 IR), no up-front genomic profiling was performed.

 

Conclusion: In SIOPEN’s LINES trial, genomic profiling in a diagnostic, real-time setting is feasible, with a success rate of 87% in analyzed cases.