I R N Verly1, A B P van Kuilenburg2, N G G M Abeling2, S M I Goorden2, M Fiocco3, F M Vaz2, M M van Noesel4, C M Zwaan5, G J L Kaspers6, J H M Merks7, H N Caron8, G A M Tytgat9. 1. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Utrecht, The Netherlands. 2. Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. 3. Mathematical Institute, Leiden University, Leiden, The Netherlands; Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands. 4. Princess Máxima Center for Pediatric Oncology/Hematology, Utrecht, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands. 5. Department of Pediatric Oncology/Hematology, Sophia Children's Hospital/Erasmus Medical Center, Rotterdam, The Netherlands. 6. Princess Máxima Center for Pediatric Oncology/Hematology, Utrecht, The Netherlands; Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands. 7. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Utrecht, The Netherlands. 8. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. 9. Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Utrecht, The Netherlands. Electronic address: G.A.M.Tytgat@prinsesmaximacentrum.nl.
Abstract
INTRODUCTION: Prognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. PATIENTS AND METHODS: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis. RESULTS: Multivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% ± 4% and 66.7% ± 18%, respectively, p = 0.001; 5-year OS of 21.8% ± 5% and 87.5% ± 12%, respectively, p < 0.001). CONCLUSIONS: Elevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis.
INTRODUCTION: Prognosis of neuroblastomapatients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. PATIENTS AND METHODS: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis. RESULTS: Multivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% ± 4% and 66.7% ± 18%, respectively, p = 0.001; 5-year OS of 21.8% ± 5% and 87.5% ± 12%, respectively, p < 0.001). CONCLUSIONS: Elevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis.
Authors: Iedan R N Verly; Yvette A H Matser; René Leen; Rutger Meinsma; Marta Fiocco; Jan Koster; Richard Volckmann; Dilara Savci-Heijink; Giuliana Cangemi; Sebastiano Barco; Linda J Valentijn; Godelieve A M Tytgat; André B P van Kuilenburg Journal: JCO Precis Oncol Date: 2022-01