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. 2021 Feb 2;13(3):572.
doi: 10.3390/cancers13030572.

Long-Term Outcome and Role of Biology within Risk-Adapted Treatment Strategies: The Austrian Neuroblastoma Trial A-NB94

Stefan Fiedler  1   2 , Inge M Ambros  2 , Evgenia Glogova  2 , Martin Benesch  3 , Christian Urban  3 , Marlene Mayer  3 , Georg Ebetsberger-Dachs  4 , Edit Bardi  1   4 , Neil Jones  5 , Agnes Gamper  5 , Bernhard Meister  6 , Roman Crazzolara  6 , Gabriele Amann  7 , Karin Dieckmann  8 , Ernst Horcher  9 , Reinhold Kerbl  10 , Bettina Brunner-Herglotz  2 , Andrea Ziegler  2 , Peter F Ambros  2 , Ruth Ladenstein  1   2   11
Affiliations

Long-Term Outcome and Role of Biology within Risk-Adapted Treatment Strategies: The Austrian Neuroblastoma Trial A-NB94

Stefan Fiedler et al. Cancers (Basel). .

Abstract

We evaluated long-term outcome and genomic profiles in the Austrian Neuroblastoma Trial A-NB94 which applied a risk-adapted strategy of treatment (RAST) using stage, age and MYCN amplification (MNA) status for stratification. RAST ranged from surgery only to intensity-adjusted chemotherapy, single or multiple courses of high-dose chemotherapy (HDT) followed by autologous stem cell rescue depending on response to induction chemotherapy, and irradiation to the primary tumor site. Segmental chromosomal alterations (SCAs) were investigated retrospectively using multi- and pan-genomic techniques. The A-NB94 trial enrolled 163 patients. Patients with localized disease had an excellent ten-year (10y) event free survival (EFS) and overall survival (OS) of 99 ± 1% and 93 ± 2% whilst it was 80 ± 13% and 90 ± 9% for infants with stage 4S and for infants with stage 4 non-MNA disease both 83 ± 15%. Stage 4 patients either >12 months or ≤12 months but with MNA had a 10y-EFS and OS of 45 ± 8% and 47 ± 8%, respectively. SCAs were present in increasing frequencies according to stage and age: in 29% of localized tumors but in 92% of stage 4 tumors (p < 0.001), and in 39% of patients ≤ 12 months but in 63% of patients > 12 months (p < 0.001). RAST successfully reduced chemotherapy exposure in low- and intermediate-risk patients with excellent long-term results while the outcome of high-risk disease met contemporary trials.

Keywords: Austrian trial A-NB94; biomarkers; neuroblastoma.

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Conflict of interest statement

The following authors declare conflict of interest: Georg Ebetsberger-Dachs–Consulting or advisory role: Novartis International AG, Amgen Inc.; Travel, accommodations, expenses: Shire PLC., Servier Laboratories. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
EFS and OS by (A) prospective International Neuroblastoma Staging System (INSS) as outlined in the A-NB94 trial; (B) post hoc grouping according to the International Neuroblastoma Risk Group (INRG) Staging System; (C) presence or absence of segmental chromosomal aberrations (SCAs); (D) effect of MYCN amplification (MNA) status in INSS stage 4 patients only.
Figure 2
Figure 2
Presence of SCAs, ATRX deletion, and TERT gain within groups by age and stage. Presence of segmental chromosomal alterations (SCAs) that were associated with a significantly lower event-free (EFS) and overall survival (OS) in a univariate analysis within groups differentiated by age (≤/>12 months) and stage by International Neuroblastoma Staging System (INSS) (localized/4S or stage 4).
See this image and copyright information in PMC

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