TY  - JOUR
A1  - Berthold, Frank
A1  - Ernst, Angela
A1  - Ackermann, Sandra
A1  - Bartenhagen, Christoph
A1  - Christiansen, Holger
A1  - Hero, Barbara
A1  - Rosswog, Carolina
A1  - Schweinitz, Dietrich von
A1  - Klingebiel, Thomas
A1  - Schmid, Irene
A1  - Simon, Thorsten
A1  - Matthias, Fischer
T1  - Genetic alterations and resectability predict outcome in patients with neuroblastoma assigned to high-risk solely by MYCN amplification
T2  - Cancers
N2  - Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
KW  - high-risk neuroblastoma
KW  - MYCN amplification
KW  - RAS pathway
KW  - p53 pathway
KW  - ALK
KW  - resectability
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62174
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621744
SN  - 2072-6694
N1  - This research received external funding. The work of CR was supported by the Else Kröner-Fresenius Foundation (2016-Kolleg-19). The Neuroblastoma trial NB97 was supported by the German Cancer Aid (Grant 70-2290-Be) and by the German Children’s Cancer Aid (Grants 96.06 and 99.03). Neuroblastoma trial NB2004 was supported by the German Cancer Aid (Grant (70107712) to FB.
VL  - 13
IS  - 17, art. 4360
SP  - 1
EP  - 15
PB  - MDPI
CY  - Basel
ER  -