TY - JOUR
T1 - Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
AU - Ambros, Inge M
AU - Tonini, Gian-Paolo
AU - Pötschger, Ulrike
AU - Gross, Nicole
AU - Mosseri, Véronique
AU - Beiske, Klaus
AU - Berbegall, Ana P
AU - Bénard, Jean
AU - Bown, Nick
AU - Caron, Huib
AU - Combaret, Valérie
AU - Couturier, Jerome
AU - Defferrari, Raffaella
AU - Delattre, Olivier
AU - Jeison, Marta
AU - Kogner, Per
AU - Lunec, John
AU - Marques, Barbara
AU - Martinsson, Tommy
AU - Mazzocco, Katia
AU - Noguera, Rosa
AU - Schleiermacher, Gudrun
AU - Valent, Alexander
AU - Van Roy, Nadine
AU - Villamon, Eva
AU - Janousek, Dasa
AU - Pribill, Ingrid
AU - Glogova, Evgenia
AU - Attiyeh, Edward F
AU - Hogarty, Michael D
AU - Monclair, Tom F
AU - Holmes, Keith
AU - Valteau-Couanet, Dominique
AU - Castel, Victoria
AU - Tweddle, Deborah A
AU - Park, Julie R
AU - Cohn, Sue
AU - Ladenstein, Ruth
AU - Beck-Popovic, Maja
AU - De Bernardi, Bruno
AU - Michon, Jean
AU - Pearson, Andrew D J
AU - Ambros, Peter F
PY - 2020/11/1
Y1 - 2020/11/1
N2 - PURPOSE: For localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODS: Diagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTS: Patients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] ± standard deviation [SD], 95% ± 2%; 5-year overall survival [OS], 99% ± 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS ± SD, 84% ± 3% in patients < 18 months of age and 75% ± 7% in patients ≥ 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS ± SD in < 18months and ≥ 18months, 96% ± 2% and 81% ± 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS ± SD in patients 1p loss and no 1p loss, 62% ± 13% and 87% ± 3%, respectively; P = .019) but not OS (5-year OS ± SD, 92% ± 8% and 97% ± 2%, respectively). In patients ≥ 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS ± SD, 48% ± 16% and 85% ± 7%, P = .033; 5-year OS ± SD, 46% ± 22% and 92% ± 6%, P = .038).CONCLUSION: Genomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
AB - PURPOSE: For localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODS: Diagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTS: Patients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] ± standard deviation [SD], 95% ± 2%; 5-year overall survival [OS], 99% ± 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS ± SD, 84% ± 3% in patients < 18 months of age and 75% ± 7% in patients ≥ 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS ± SD in < 18months and ≥ 18months, 96% ± 2% and 81% ± 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS ± SD in patients 1p loss and no 1p loss, 62% ± 13% and 87% ± 3%, respectively; P = .019) but not OS (5-year OS ± SD, 92% ± 8% and 97% ± 2%, respectively). In patients ≥ 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS ± SD, 48% ± 16% and 85% ± 7%, P = .033; 5-year OS ± SD, 46% ± 22% and 92% ± 6%, P = .038).CONCLUSION: Genomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
KW - Age Factors
KW - Chromosome Aberrations
KW - Chromosomes, Human, Pair 1
KW - Chromosomes, Human, Pair 11
KW - Clinical Trials as Topic
KW - Diploidy
KW - Gene Amplification
KW - Genomics
KW - Humans
KW - Infant
KW - N-Myc Proto-Oncogene Protein/genetics
KW - Neoplasm Staging
KW - Neuroblastoma/genetics
KW - Prognosis
KW - Progression-Free Survival
KW - Survival Rate
U2 - 10.1200/JCO.18.02132
DO - 10.1200/JCO.18.02132
M3 - Article
C2 - 32903140
VL - 38
SP - 3685
EP - 3697
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 31
ER -