Targeting ALK in relapsed high-risk neuroblastoma: real-world insights from the SACHA-France study (was selected for Fire-session)

Methods: Neuroblastoma samples with >60% cellularity were analyzed by multi-locus/pangenomic techniques (array-CGH n=49; SNP-arrays n=285; MLPA n=9).Genomic profiles were centrally reviewed, results entered in SIOPEN-R-NET-database, and clinicallyrelevant conclusion returned to clinicians within six weeks following diagnosis.According to genomic profile, MYCN-non-amplified tumors were classified in those containing only numerical chromosome abnormalities (NCA) and those harboring neuroblastoma recurrent SCA (1p/3p/4p/11q deletions; 1q/2p/17q gains), with/ without NCA.Non-contributive genomic profiles included samples with low tumor-cell content, flat copy-number profile or nonrecurrent SCA.Results: 1190 samples from 1023 patients were analyzed (n=518 LR, n=263 IR, n=242 clinical screening-failure).A genomic profile could be determined in 621 patients (NCA n=387/SCA n=234); 402 patients showed non-contributive genomic profile (n=37 with non-recurrent SCA).A clinically decision-making genomic profile was determined in 595 patients: n=429 LR (NCA: n=313, 73%; SCA: n=116, 27%), n=166 IR (NCA: n=56, 34%; SCA: n=110, 66%).The frequency of NCA/SCA varied between different patient groups: in localized unresectable MYCN-non-amplified neuroblastoma patients 18 months (m) (n=175), n=135 (77%)/n=40 (23%); in same patients >18m (n=67), n=20 (30%)/ n=47 (70%); in patients with disseminated MYCN-non-amplified neuroblastoma 12m (n=195), n=126 (65%)/n=69 (35%) respectively.Concerning recurrent SCA, 1p/3p/4p/11q-deletions and 1q/2p/17q-gains were present in 24.4%/15.8%/17.9%/36.3%and 11.5%/31.6%/60.6% of patients with SCA, respectively.Conclusions: In SIOPEN-LINES trial, tumor genomic profiling at diagnosis identified recurrent SCA with higher frequency in older patients and those with disseminated disease.In-depth multiomics analyses including NGS-panel sequencing and expression profiling will be performed for patients with relapse whenever possible.