Background: In neuroblastoma, a genomic profile characterized by segmental chromosome alterations is associated with higher risk of relapse and poorer outcome. Methods: SIOPEN has recently launched the LINES trial (Low and Intermediate Neuroblastoma European Study). In order to maintain or improve the excellent outcome inlow risk patients, whilst diminishing overall treatment burden whenever possible, treatment is stratified according to the genomic profile in addition to clinical parameters. In intermediate risk patients, the genomic profile is studied prospectively whenever possible. NB samples that contain >60% of tumor cells are analyzed by a multi-locus or pangenomic technique such as MLPA, array-CGH or SNP-arrays. The genomic profile results are centrally reviewed, the result entered in the SIOPEN-R-NET database, and the clinically relevant conclusion is returned to the treating clinician within six weeks after diagnosis. In tumors without MYCN amplification, 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 numerical alterations. Results: To date, for 65 enrolled patients (45 LR, 20 IR), a genomic profile could be determined in 44 patients (34 NCA, 10 SCA). For 7 patients, the obtained genomic profile could not be classified according to the previously defined criteria, either because no copy number changes were seen (n=3), or because atypical segmental chromosome changes were observed, for which the prognostic relevance has not been clearly established yet (n=4). The latter included a small interstitial deletion of chromosome 8p, a small distal deletion of chromosome 3p, a chromosome 17p deletion and a focal amplification of 12q14 encompassing the CDK4/MDM2 genes. For 14 other cases, no up-front genomic profiling was performed. Conclusion: In SIOPEN’s LINES trial, in which a genomic profile is used to stratify treatment in all low-risk patients, genomic profiling in a diagnostic, real-time setting is proving feasible.

Genomic Profiling in Low and Intermediate Risk Neuroblastoma to Refine Treatment Stratification and Improve Patient Outcome - LINES: a SIOPEN Trial.

DI CATALDO, Andrea;
2014

Abstract

Background: In neuroblastoma, a genomic profile characterized by segmental chromosome alterations is associated with higher risk of relapse and poorer outcome. Methods: SIOPEN has recently launched the LINES trial (Low and Intermediate Neuroblastoma European Study). In order to maintain or improve the excellent outcome inlow risk patients, whilst diminishing overall treatment burden whenever possible, treatment is stratified according to the genomic profile in addition to clinical parameters. In intermediate risk patients, the genomic profile is studied prospectively whenever possible. NB samples that contain >60% of tumor cells are analyzed by a multi-locus or pangenomic technique such as MLPA, array-CGH or SNP-arrays. The genomic profile results are centrally reviewed, the result entered in the SIOPEN-R-NET database, and the clinically relevant conclusion is returned to the treating clinician within six weeks after diagnosis. In tumors without MYCN amplification, 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 numerical alterations. Results: To date, for 65 enrolled patients (45 LR, 20 IR), a genomic profile could be determined in 44 patients (34 NCA, 10 SCA). For 7 patients, the obtained genomic profile could not be classified according to the previously defined criteria, either because no copy number changes were seen (n=3), or because atypical segmental chromosome changes were observed, for which the prognostic relevance has not been clearly established yet (n=4). The latter included a small interstitial deletion of chromosome 8p, a small distal deletion of chromosome 3p, a chromosome 17p deletion and a focal amplification of 12q14 encompassing the CDK4/MDM2 genes. For 14 other cases, no up-front genomic profiling was performed. Conclusion: In SIOPEN’s LINES trial, in which a genomic profile is used to stratify treatment in all low-risk patients, genomic profiling in a diagnostic, real-time setting is proving feasible.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/107166
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