Urinary Catecholamines Predict Relapse During Complete Remission in High-Risk Neuroblastoma

JCO Precision Oncology, vol. 9, pp. e2400491

Abstract

PURPOSE Urinary catecholamine metabolites are well-known biomarkers for the diagnosis (Dx) of neuroblastoma, but their clinical significance in determining therapy response during treatment is not well established. Therefore, catecholamines are not included in criteria for assessing response and complete remission (CR). This study investigated the use of urinary catecholamines in response monitoring and predicting survival outcomes. METHODS From 2005 to 2021, a panel of eight urinary catecholamines were measured in patients with high-risk neuroblastoma at Dx and at standard evaluation moments during treatment. At the same time points, response and CR were assessed according to the revised International Neuroblastoma Response Criteria. RESULTS The total cohort consists of 153 high-risk patients, and at least one of the eight metabolites was elevated (ie, catecholamine status positive) in 141 of 146 (97%), 104 of 128 (81%), and 39 of 69 (57%) patients at Dx, postinduction, and at CR, respectively. Primary tumor resection significantly reduced catecholamine levels ( P < .01). A positive catecholamine status at Dx, during treatment, and at the end of treatment was not significantly associated with event-free survival (EFS) or overall survival (OS). However, in patients who achieved CR, those with a positive catecholamine status had poor EFS (38% v 80%, respectively; P < .01) and OS (52% v 86%, respectively; P = .01) compared with those with a negative catecholamine status. Notably, 3-methoxytyramine levels at CR seem to be a prognostic marker for poor OS (hazard ratio, 7.5 [95% CI, 2.0 to 28.6]). CONCLUSION Catecholamine measurements contribute to the assessment of CR and identifies patients with high-risk neuroblastoma with an increased risk of relapse and death.

Authors 15

1. Yvette A.H. Matser

   Princess Máxima Center

   Affiliation as printed

   Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

2. Atia Samim

   University Medical Center Utrecht · Princess Máxima Center

   Affiliation as printed

   Division of Imaging and Oncology, University Medical Center, Utrecht, the Netherlands

   Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

3. Marta F. Fiocco Aachen Department of Biomedical Data Science Section Medical Statistics Mathematical Institute

   Leiden University · Leiden University Medical Center · Princess Máxima Center

   Affiliation as printed

   Department of Biomedical Data Science, Section Medical Statistics, Leiden University Medical Centre, Leiden, the Netherlands

   Mathematical Institute, Leiden University, Leiden, the Netherlands

   Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

4. Marieke van de Mheen

   Princess Máxima Center

   Affiliation as printed

   Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

5. Maria van der Ham

   Wilhelmina Children's Hospital

   Affiliation as printed

   Department of Genetics, Section Metabolic Diagnostics, Wilhelmina Children's Hospital, Utrecht, the Netherlands

6. Monique G.M. de Sain–van der Velden

   Wilhelmina Children's Hospital

   Affiliation as printed

   Department of Genetics, Section Metabolic Diagnostics, Wilhelmina Children's Hospital, Utrecht, the Netherlands

7. Nanda M. Verhoeven‐Duif

   Wilhelmina Children's Hospital

   Affiliation as printed

   Department of Genetics, Section Metabolic Diagnostics, Wilhelmina Children's Hospital, Utrecht, the Netherlands

8. Martine van Grotel

   Princess Máxima Center

   Affiliation as printed

   Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

9. Kathelijne C.J.M. Kraal

   Princess Máxima Center

   Affiliation as printed

   Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

10. Miranda P. Dierselhuis

    Princess Máxima Center

    Affiliation as printed

    Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

11. Natasha K. A. van Eijkelenburg

    Princess Máxima Center

    Affiliation as printed

    Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

12. Karin P.S. Langenberg

    Princess Máxima Center

    Affiliation as printed

    Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

13. Max M. van Noesel

    University Medical Center Utrecht · Princess Máxima Center

    Affiliation as printed

    Division of Imaging and Oncology, University Medical Center, Utrecht, the Netherlands

    Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

14. André B. P. Kuilenburg

    Amsterdam University Medical Centers · Cancer Center Amsterdam

    Affiliation as printed

    Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands

    Laboratory Genetic Metabolic Diseases, Amsterdam UMC, Free University Amsterdam, Amsterdam, the Netherlands

15. Lieve Tytgat

    Utrecht University · University Medical Center Utrecht · Princess Máxima Center

    Affiliation as printed

    Department of Genetics, Utrecht University Medical Center, Utrecht University, Utrecht, the Netherlands

    Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands