Browsing by Author "Ambros, I.M."
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- Age-dependency of the prognostic impact of tumor genomics in localized resectable MYCN non-amplified neuroblastomas Report from the SIOPEN Biology Group on the LNESG TrialsPublication . Ambros, I.M.; Tonini, G.P.; Gross, N.; Mosseri, V.; Pötschger, U.; Beiske, K.; Berbegall, A.P.; Bénard, J.; Bown, N.; Caron, H.; Combaret, V.; Couturier, J.; Defferrari, R.; Delattre, O.; Jeison, M.; Kogner, P.; Lunec, J.; Marques, B.; Martinsson, T.; Mazzocco, K.; Noguera, R.; Schleiermacher, G.; Valent, A.; Van Roy, N.; Villamon, E.; Janousek, D.; Pribill, I.; Glogova, E.; Attiyeh, E.F.; Hogarty, M.D.; Monclair, T.; Holmes, K.; Valteau-Couanet, D.; Pearson ADJ, A.D.J.; Castel, V.; Tweddle, D.A.; Park, J.R.; Cohn, S.; Ladenstein, R.; Beck-Popovic, M.; De Bernardi, B.; Michon, J.; Ambros, P.F.BACKGROUND: Biology based treatment reduction, i.e. surgery alone also in case of not totally resected tumors, was advised in neuroblastoma patients with localized resectable disease without MYCN amplification. However, whether the genomic background of these tumors may influence outcome was unknown and therefore scrutinized in a meta-analysis comprising two prospective therapy studies and a ‘validation’ cohort. PATIENTS AND METHODS: Diagnostic samples were derived from 406 INSS stages 1/2A/2B tumors from three cohorts: LNESGI/II and COG. Genomic data were analyzed in two age groups (cut-off: 18 months) and quality controlled by the SIOPEN Biology Group. RESULTS: In both patient age groups stage 2 tumors led to similarly reduced event-free survival (5y-EFS: 83+3% versus 80+4%), but overall survival was only decreased in patients >18m (5y-OS: 97+1% versus 87+4%; p=0.001). In the latter age subgroup, only tumors with SCA led to relapses, with 11q loss as the strongest marker (5y-EFS: 40+15% versus 89+5%; p<0,001). Below 18m, EFS but not OS was decreased only in case of 1p loss (5y-EFS: 62+13% versus 85+3%; p=0,041). SCAs were associated with worse OS only in patients >18m but not <18m. CONCLUSION: The tumor genomic make-up of resectable non-MYCN amplified stage 2 neuroblastomas has a distinct age-dependent prognostic impact in neuroblastoma patients. While in the younger age group tumors with unfavourable (SCA) and favorable genetics showed relapses, both without worsening OS, in the older age group only tumors with unfavorable genetics led to relapses and decreased OS.
- Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplificationPublication . Defferrari, R.; Mazzocco, K.; Ambros, I.M.; Ambros, P.F.; Bedwell, C.; Beiske, K.; Bénard, J.; Berbegall, A.P.; Bown, N.; Combaret, V.; Couturier, J.B.; Erminio, G.; Gambini, C.; Garaventa, A.; Gross, N.; Haupt, R.; Kohler, J.; Jeison, M.; Lunec, J.; Marques, B.; Martinsson, T.; Noguera, R.; Parodi, S.; Schleiermacher, G.; Tweddle, D.A.; Valent, A.B.; Van Roy, N.; Vicha, A.; Villamon, E.; Tonini, G.P.BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018). CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.