TY - JOUR
T1 - Central nervous system relapse in high-risk stage 4 neuroblastoma: The HR-NBL1/SIOPEN trial experience
AU - Berlanga, Pablo
AU - Pasqualini, Claudia
AU - Pötschger, Ulrike
AU - Sangüesa, C.
AU - Castellani, Maria Rita
AU - Canete, Adela
AU - Luksch, Roberto
AU - Elliot, Martin
AU - Schreier, Günter
AU - Kropf, Martin
AU - Morgenstern, Daniel
AU - Papadakis, Vassilios
AU - Ash, Shifra
AU - Ruud, Ellen
AU - Brock, Penelope
AU - Wieczorek, Aleksander
AU - Kogner, Per
AU - Trahair, Toby
AU - Ambros, Peter
AU - Boterberg, Tom
AU - Castel, Victoria
AU - Valteau-Couanet, Dominique
AU - Ladenstein, Ruth
PY - 2021
Y1 - 2021
N2 - Background: There is rising concern on the impact of new strategies, such as highdose
chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma
(HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first
recurrence in the central nervous system (CNS) in HR-NBL.
Patients and methods: Data from patients with stage 4V HR-NBL included from February
2002 to June 2015 in the prospective HR-NBL trial of the European International Society
of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis,
treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally
reviewed.
Results: The 1977 included patients had a median age of 3 years (1 daye20 years); 1163 were
boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%,
representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival
was 25 6% and 8 4%, respectively. Higher risk of CNS recurrence was associated with
female sex (hazard ratio [HR] Z 2.0 [95% confidence interval {CI}: 1.1e3.5]; P Z 0.016),
MYCN-amplification (HR Z 2.4 [95% CI: 1.2e4.4]; P Z 0.008), liver (HR Z 2.5 [95% CI:
1.2e5.1]; P Z 0.01) or >1 metastatic compartment involvement (HR Z 7.1 [95% CI: 1.0
e48.4]; PZ0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher
risk of CNS recurrence. Stable incidence of CNS relapse was reported over time.
Conclusions: The risk of CNS recurrence is linked to both patient and disease characteristics,
with neither impact of HDC nor immunotherapy. These findings support the current treatment
strategy and do not justify a CNS prophylactic treatment.
ª 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
AB - Background: There is rising concern on the impact of new strategies, such as highdose
chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma
(HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first
recurrence in the central nervous system (CNS) in HR-NBL.
Patients and methods: Data from patients with stage 4V HR-NBL included from February
2002 to June 2015 in the prospective HR-NBL trial of the European International Society
of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis,
treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally
reviewed.
Results: The 1977 included patients had a median age of 3 years (1 daye20 years); 1163 were
boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%,
representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival
was 25 6% and 8 4%, respectively. Higher risk of CNS recurrence was associated with
female sex (hazard ratio [HR] Z 2.0 [95% confidence interval {CI}: 1.1e3.5]; P Z 0.016),
MYCN-amplification (HR Z 2.4 [95% CI: 1.2e4.4]; P Z 0.008), liver (HR Z 2.5 [95% CI:
1.2e5.1]; P Z 0.01) or >1 metastatic compartment involvement (HR Z 7.1 [95% CI: 1.0
e48.4]; PZ0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher
risk of CNS recurrence. Stable incidence of CNS relapse was reported over time.
Conclusions: The risk of CNS recurrence is linked to both patient and disease characteristics,
with neither impact of HDC nor immunotherapy. These findings support the current treatment
strategy and do not justify a CNS prophylactic treatment.
ª 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
KW - Neuroblastoma; Central nervous system; Relapse; High-dose chemotherapy; Anti-GD2
KW - Neuroblastoma; Central nervous system; Relapse; High-dose chemotherapy; Anti-GD2
U2 - 10.1016/J.EJCA.2020.10.020
DO - 10.1016/J.EJCA.2020.10.020
M3 - Article
SN - 0959-8049
SP - 1
EP - 8
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 144
ER -