TY - JOUR
T1 - A nomogram of clinical and biologic factors to predict survival in children newly diagnosed with high-risk neuroblastoma
T2 - An International Neuroblastoma Risk Group project
AU - Moreno, Lucas
AU - Guo, Dongjing
AU - Irwin, Meredith S.
AU - Berthold, Frank
AU - Hogarty, Michael
AU - Kamijo, Takehiko
AU - Morgenstern, Daniel
AU - Pasqualini, Claudia
AU - Ash, Shifra
AU - Potschger, Ulrike
AU - Ladenstein, Ruth
AU - Valteau-Couanet, Dominique
AU - Cohn, Susan L.
AU - Pearson, Andrew D.J.
AU - London, Wendy B.
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - biomarkers
KW - high-risk neuroblastoma
KW - nomogram
KW - prognostic factors
KW - risk stratification
KW - ultra-high-risk
UR - http://www.scopus.com/inward/record.url?scp=85096636901&partnerID=8YFLogxK
U2 - 10.1002/pbc.28794
DO - 10.1002/pbc.28794
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C2 - 33205902
AN - SCOPUS:85096636901
SN - 1545-5009
VL - 68
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 3
M1 - e28794
ER -
