Iedan R N Verly1, André B P van Kuilenburg2, Nico G G M Abeling2, Susan M I Goorden2, Marta Fiocco3, Frédéric M Vaz2, Max M van Noesel4, C Michel Zwaan5, GertJan L Kaspers6, Johannes H M Merks7, Huib N Caron7, Godelieve A M Tytgat8. 1. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Lundlaan 6, 3584 EA Utrecht, The Netherlands. 2. Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 3. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Eindhovenweg 20, 2333 ZC Leiden, The Netherlands; Mathematical Institute, Leiden University, Niels Bohrweg 1, 2333 CA Leiden, The Netherlands. 4. Princess Máxima Center for Pediatric Oncology/Hematology, Lundlaan 6, 3584 EA Utrecht, The Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. 5. Department of Pediatric Oncology/Hematology, Sophia Children's Hospital/Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. 6. Department of Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. 7. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 8. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Lundlaan 6, 3584 EA Utrecht, The Netherlands. Electronic address: G.A.M.Tytgat@prinsesmaximacentrum.nl.
Abstract
INTRODUCTION: Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. PATIENTS AND METHODS: Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients. RESULTS: Elevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel. CONCLUSIONS: Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients.
INTRODUCTION:Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. PATIENTS AND METHODS: Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients. RESULTS: Elevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel. CONCLUSIONS: Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients.
Authors: Michaela Kuhlen; Christina Pamporaki; Marina Kunstreich; Stefan A Wudy; Michaela F Hartmann; Mirko Peitzsch; Christian Vokuhl; Guido Seitz; Michael C Kreissl; Thorsten Simon; Barbara Hero; Michael C Frühwald; Peter Vorwerk; Antje Redlich Journal: Front Endocrinol (Lausanne) Date: 2022-06-17 Impact factor: 6.055
Authors: Etienne C Gozlan; Boris I Chobrutskiy; Saif Zaman; Michelle Yeagley; George Blanck Journal: J Mol Neurosci Date: 2021-03-05 Impact factor: 3.444