TY - JOUR
T1 - Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma
T2 - A SIOPEN Study
AU - Hartley, Hannah E.
AU - Fong, Fang Chyi
AU - Gabriel, Alem S.
AU - Stevenson, Louise K.
AU - Beckett, Emily
AU - Allinson, Lisa M.
AU - Goodman, Angharad
AU - Potts, Aaron
AU - Whittle, Emily
AU - Barford, Ruby
AU - Lamparelli, Alice
AU - Herd, Fiona
AU - Mazzocco, Katia
AU - Pezzolo, Annalisa
AU - Morini, Martina
AU - Ardito, Martina
AU - Eva, Alessandra
AU - Ognibene, Marzia
AU - Fischer, Matthias
AU - Ackermann, Sandra
AU - Rosswog, Carolina
AU - Hero, Barbara
AU - Smith, Graham R.
AU - Unsworth, Adrienne A.
AU - McCorkindale, Michael
AU - George, Sally L.
AU - Tall, Jennifer
AU - Molenaar, Jan J.
AU - Matser, Yvette
AU - Langenberg, Karin
AU - Tytgat, Godelieve
AU - Noguera, Rosa
AU - Berbegall, Ana P.
AU - de Mora, Jaime Font
AU - Combaret, Valérie
AU - Pierron, Gaelle
AU - Mühlethaler-Mottet, Annick
AU - Schoumans, Jacqueline
AU - Tchinda, Joëlle
AU - Banzola, Irina
AU - Jeison, Marta
AU - Hameiri-Grossman, Michal
AU - Beiske, Klaus H.
AU - Auger, Nathalie
AU - Van Roy, Nadine
AU - Basta, Nermine O.
AU - McNally, Richard J.Q.
AU - Taschner-Mandl, Sabine
AU - Papadakis, Vassilios
AU - Di Cataldo, Andrea
AU - Wheeler, Kate
AU - Bermúdez, Jose D.
AU - Beck-Popovic, Maja
AU - Segura, Vanessa
AU - Canete, Adela
AU - Schleiermacher, Gudrun
AU - Tweddle, Deborah A.
N1 - Publisher Copyright:
© 2026 by American Society of Clinical Oncology
PY - 2026/7
Y1 - 2026/7
N2 - PURPOSE – Intermediate-risk neuroblastoma patients older than 18 months, with non–MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup. METHODS – We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival. RESULTS – Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS. CONCLUSION – Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.
AB - PURPOSE – Intermediate-risk neuroblastoma patients older than 18 months, with non–MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup. METHODS – We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival. RESULTS – Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS. CONCLUSION – Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.
UR - https://www.scopus.com/pages/publications/105046796810
U2 - 10.1200/PO-26-00045
DO - 10.1200/PO-26-00045
M3 - Article
C2 - 42385103
AN - SCOPUS:105046796810
SN - 2473-4284
VL - 10
JO - JCO precision oncology
JF - JCO precision oncology
IS - 7
ER -