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. 2021 Mar;68(3):e28794.
doi: 10.1002/pbc.28794. Epub 2020 Nov 18.

A nomogram of clinical and biologic factors to predict survival in children newly diagnosed with high-risk neuroblastoma: An International Neuroblastoma Risk Group project

Lucas Moreno  1 , Dongjing Guo  2 , Meredith S Irwin  3 , Frank Berthold  4 , Michael Hogarty  5 , Takehiko Kamijo  6 , Daniel Morgenstern  3 , Claudia Pasqualini  7 , Shifra Ash  8 , Ulrike Potschger  9 , Ruth Ladenstein  9 , Dominique Valteau-Couanet  7 , Susan L Cohn  10 , Andrew D J Pearson  11 , Wendy B London  2
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A nomogram of clinical and biologic factors to predict survival in children newly diagnosed with high-risk neuroblastoma: An International Neuroblastoma Risk Group project

Lucas Moreno et al. Pediatr Blood Cancer. 2021 Mar.

Abstract

Background: Long-term outcome remains poor for children with high-risk neuroblastoma (five-year overall survival [OS] ∼50%). Our objectives were to (a) identify prognostic biomarkers and apply them in a nomogram to identify the subgroup of ultra-high-risk patients at highest risk of disease progression/death, for whom novel frontline therapy is urgently needed; and (b) validate the nomogram in an independent cohort.

Methods: A total of 1820 high-risk patients (≥18 months old with metastatic neuroblastoma), diagnosed 1998-2015, from the International Neuroblastoma Risk Groups (INRG) Data Commons were analyzed in a retrospective cohort study. Using multivariable Cox regression of OS from diagnosis, a nomogram was created from prognostic biomarkers to predict three-year OS. External validation was performed using the SIOPEN HR-NBL1 trial cohort (n = 521), evidenced by receiver operating characteristic curves.

Results: The nomogram, including MYCN status (P < 0.0001), lactate dehydrogenase (LDH) (P = 0.0007), and presence of bone marrow metastases (P = 0.004), had robust performance and was validated. Applying the nomogram at diagnosis (a) gives prognosis of an individual patient and (b) identifies patients predicted to have poor outcome (three-year OS was 30% ± 5% for patients with a nomogram score of > 82 points; 58% ± 1% for those ≤82 points). Median follow-up time was 5.5 years (range, 0-14.1).

Conclusions: In high-risk neuroblastoma, a novel, publicly available nomogram using prognostic biomarkers (MYCN status, LDH, presence of bone marrow metastases; https://neuroblastoma.shinyapps.io/High-Risk-Neuroblastoma-Nomogram/) has the flexibility to apply a clinically suitable and context-specific cutoff to identify patients at highest risk of death. This will facilitate testing urgently needed new frontline treatment options to improve outcome for these children.

Keywords: biomarkers; high-risk neuroblastoma; nomogram; prognostic factors; risk stratification; ultra-high-risk.

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REFERENCES

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