POC34 Genomic profiling in low risk neuroblastoma to refine treatment stratification and improve patient outcome – LINES: a SIOPEN Trial Gudrun Schleiermacher, Institut Curie, Paris, France; Kate Wheeler, Children’sHospital, Oxford, United Kingdom; Véronique Mosseri, Institut Curie, Paris, France; Adela Canete, Hospital Infantil La Fe, Valencia, Spain; Andrea di Cataldo, University of Catania, Catania, Italy; Vassilios Papadakis, Aghia Sofia Children’s Hospital, Athens, Greece; Raffaella Defferrari, Gaslini Childrens’ Hospital, Genoa, Italy; Katia Mazzocco, Gaslini Childrens’ Hospital, Genoa, Italy; Rosa Noguera, University of Valencia, Valencia, Spain; Jean Michon, Institut Curie, Paris, France; Peter Ambros, Children’s Cancer Research Institute, Vienna, Austria; For SIOPEN and the SIOPEN Biology committee Background: In low risk neuroblastoma (NB), new strategies are required to further stratify therapy in order to minimize treatment burden while maintaining excellent survival. Recent studies have shown that genomic profiles with segmental chromosome alterations are associated with a poorer event free survival, requiring more intensive salvage treatment. Methods: SIOPEN has launched a European trial, LINES (Low and Intermediate Neuroblastoma European Study), with the intention, in low risk NB patients, to maintain or improve the excellent outcome, while decreasing the overall treatment burden. In addition to clinical parameters, treatment is stratified according to the tumor genomic. Results: NB samples that contain >60% of tumor cells are analyzed in real-time by a multi-locus or pangenomic technique such as MLPA, array-CGH or SNParrays. The genomic profile results are centrally reviewed by two independent reviewers using the expanded SIOPEN-R-NET database, and the conclusion is returned to the treating center within 3 weeks. Genomic profiles are classified into two large classes: those harboring numerical chromosome alterations (NCA) only, versus those harboring segmental chromosome alterations (SCA) known to frequently occur in NB, with or without NCA. For low risk NB patients without MYCN amplification, with stage L2, age <18 months, or stage Ms, age <12 months, treatment is then stratified into 6 different groups according to stage, the presence or absence of life threatening symptoms and the genomic profile. In infants with L2 disease without symptoms, absence of SCA identifies a group of patients for whom the hypothesis that observation only might be sufficient treatment is tested in a randomized phase III trial. When SCAs are present, upfront chemotherapy is proposed. Conclusion: SIOPEN has launched a prospective trial, LINES, in which, to stratify treatment, a genomic profile defined by the presence or absence of typical SCAs is used in addition to the standard clinical parameters. Email: gudrun.schleiermacher@curie.net
Genomic profiling in low risk neuroblastoma to refine treatment stratification and improve patient outcome – LINES: a SIOPEN Trial. Toronto, Canada, 18-21 June, 2012, POC 34 pag.190.
DI CATALDO, Andrea;
2012-01-01
Abstract
POC34 Genomic profiling in low risk neuroblastoma to refine treatment stratification and improve patient outcome – LINES: a SIOPEN Trial Gudrun Schleiermacher, Institut Curie, Paris, France; Kate Wheeler, Children’sHospital, Oxford, United Kingdom; Véronique Mosseri, Institut Curie, Paris, France; Adela Canete, Hospital Infantil La Fe, Valencia, Spain; Andrea di Cataldo, University of Catania, Catania, Italy; Vassilios Papadakis, Aghia Sofia Children’s Hospital, Athens, Greece; Raffaella Defferrari, Gaslini Childrens’ Hospital, Genoa, Italy; Katia Mazzocco, Gaslini Childrens’ Hospital, Genoa, Italy; Rosa Noguera, University of Valencia, Valencia, Spain; Jean Michon, Institut Curie, Paris, France; Peter Ambros, Children’s Cancer Research Institute, Vienna, Austria; For SIOPEN and the SIOPEN Biology committee Background: In low risk neuroblastoma (NB), new strategies are required to further stratify therapy in order to minimize treatment burden while maintaining excellent survival. Recent studies have shown that genomic profiles with segmental chromosome alterations are associated with a poorer event free survival, requiring more intensive salvage treatment. Methods: SIOPEN has launched a European trial, LINES (Low and Intermediate Neuroblastoma European Study), with the intention, in low risk NB patients, to maintain or improve the excellent outcome, while decreasing the overall treatment burden. In addition to clinical parameters, treatment is stratified according to the tumor genomic. Results: NB samples that contain >60% of tumor cells are analyzed in real-time by a multi-locus or pangenomic technique such as MLPA, array-CGH or SNParrays. The genomic profile results are centrally reviewed by two independent reviewers using the expanded SIOPEN-R-NET database, and the conclusion is returned to the treating center within 3 weeks. Genomic profiles are classified into two large classes: those harboring numerical chromosome alterations (NCA) only, versus those harboring segmental chromosome alterations (SCA) known to frequently occur in NB, with or without NCA. For low risk NB patients without MYCN amplification, with stage L2, age <18 months, or stage Ms, age <12 months, treatment is then stratified into 6 different groups according to stage, the presence or absence of life threatening symptoms and the genomic profile. In infants with L2 disease without symptoms, absence of SCA identifies a group of patients for whom the hypothesis that observation only might be sufficient treatment is tested in a randomized phase III trial. When SCAs are present, upfront chemotherapy is proposed. Conclusion: SIOPEN has launched a prospective trial, LINES, in which, to stratify treatment, a genomic profile defined by the presence or absence of typical SCAs is used in addition to the standard clinical parameters. Email: gudrun.schleiermacher@curie.netI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
