Age at diagnosis as a prognostic factor in South African children with neuroblastoma

Jaques van Heerden; Tonya M Esterhuizen; Marc Hendricks; Janet Poole; Ané Büchner; Gita Naidu; Jan du Plessis; Barry van Emmenes; Ronelle Uys; G P Hadley; Mariana Kruger

doi:10.1002/pbc.28878

Age at diagnosis as a prognostic factor in South African children with neuroblastoma

Pediatr Blood Cancer. 2021 Apr;68(4):e28878. doi: 10.1002/pbc.28878. Epub 2021 Jan 23.

Authors

Jaques van Heerden^{1

2}, Tonya M Esterhuizen³, Marc Hendricks⁴, Janet Poole⁵, Ané Büchner⁶, Gita Naidu⁷, Jan du Plessis⁸, Barry van Emmenes⁹, Ronelle Uys¹, G P Hadley¹⁰, Mariana Kruger¹

Affiliations

¹ Department of Paediatric Haematology and Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.
² Paediatric Haematology and Oncology, Department of Paediatrics, Antwerp University Hospital, Edegem, Belgium.
³ Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁴ Department of Paediatrics and Child Health, Faculty of Health Sciences, Paediatric Haematology and Oncology Service, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
⁵ Faculty of Health Sciences, Division of Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Cape Town, South Africa.
⁶ Paediatric Haematology and Oncology, Department of Paediatrics, University of Pretoria, Steve Biko Academic Hospital, Pretoria, South Africa.
⁷ Faculty of Health Sciences, Division of Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.
⁸ Department of Paediatrics, Faculty of Health Sciences, University of the Free State, Division of Paediatric Haematology and Oncology, Universitas Hospital, Bloemfontein, South Africa.
⁹ Division of Paediatric Haematology and Oncology Hospital, Department of Paediatrics, Frere Hospital, East London, Eastern Cape, South Africa.
¹⁰ Department of Paediatric Surgery, Faculty of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Berea, South Africa.

PMID: 33484106
DOI: 10.1002/pbc.28878

Abstract

Purpose: Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point.

Methods: Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests.

Results: The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis.

Conclusion: The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.

Keywords: age of diagnosis; low- and middle-income country; neuroblastoma; prognostic factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Child
Child, Preschool
Cohort Studies
Female
Humans
Infant
Male
Neuroblastoma / diagnosis*
Neuroblastoma / epidemiology
Prognosis
South Africa
Survival Analysis