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Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials

R. Ladenstein, B. Lambert, U. Pötschger, MR. Castellani, V. Lewington, Z. Bar-Sever, A. Oudoux, A. Śliwińska, K. Taborska, L. Biassoni, GA. Yanik, A. Naranjo, MT. Parisi, BL. Shulkin, H. Nadel, MJ. Gelfand, KK. Matthay, JR. Park, SG. Kreissman,...

. 2018 ; 45 (2) : 292-305. [pub] 20170923

Language English Country Germany

Document type Clinical Trial, Journal Article, Validation Study

Persistent link   https://www.medvik.cz/link/bmc19001175

BACKGROUND: Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations. RESULTS: The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0-6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response. CONCLUSIONS: Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.

Children's Cancer Research Institute Zimmermannplatz 10 1090 Vienna Austria

Children's Cancer Research Institute Zimmermannplatz 10 1090 Vienna Austria Medical University Department of Paediatrics Vienna Austria

Children's Memorial Health Institute Warsaw Poland

Children's Oncology Group Statistics and Data Center University of Florida Gainesville FL USA

Department of Diagnostic Imaging St Jude Children's Research Hospital Memphis TN USA

Department of Nuclear Medicine Lille Oscar Lambret Center Lille France

Department of Pediatrics Duke University Medical Center Durham NC USA

Department of Pediatrics University of California San Francisco School of Medicine San Francisco CA USA

Department of Pediatrics University of Washington School of Medicine Seattle Children's Hospital Seattle WA USA

Department of Radiology BC Children's Hospital Vancouver BC Canada

Department of Radiology Cincinnati Children's Hospital Medical Center Cincinnati OH USA

Department of Radiology University of Washington School of Medicine Seattle Children's Hospital Seattle WA USA

Great Ormond Street Hospital for Children NHS Foundation Trust London UK

Guy's and St Thomas' NHS Foundation Trust London UK

Institute of Radiology Clinique de La Source Lausanne Switzerland

Motol University Hospital Prague Czech Republic

Nuclear Medicine Division Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Pediatric and Adolescent Oncology Gustave Roussy Institute Université Paris Sud Villejuif France

Radiology and Nuclear Medicine Ghent University Ghent Belgium

Schneider Children's Medical Center of Israel Petah Tikva Israel

University of Michigan Medical Center Ann Arbor MI USA

References provided by Crossref.org

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$a Yanik, Gregory A $u University of Michigan Medical Center, Ann Arbor, MI, USA.
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$a Parisi, Marguerite T $u Department of Radiology, University of Washington School of Medicine/ Seattle Children's Hospital, Seattle, WA, USA.
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