Evaluation rétrospective de la signification pronostique de la méthoxytyramine plasmatique dans le suivi d’enfants atteints de neuroblastome de risque bas et intermédiaire

Résumé 0

Background and objective: Neuroblastoma (NB) accounts for 10% of the malignancies in children and is responsible for 15% of cancer related child mortality. Urine vanillylmandelic acid (VMA) and homovanillic acid (HVA) are the current gold standard for the diagnosis of NB. Urine harvesting might be particularly challenging considering the early childhood occurrence of NB, and this technique provides only suboptimal diagnostic sensitivity (70- 80%). Based on previous studies, there was evidence for a superior sensitivity of methoxylated plasma catecholamine derived metabolites called metanephrines. This project was designed to give a first retrospective insight on the use of plasma metanephrines and, particularly the free methoxytyramine as a biomarker for a diagnosis and follow-up approach of NB. Patients and methods: Retrospective study of a panel of 15 patients with low to intermediate risk NB. Patients were reviewed for clinical data and follow-up of imaging and laboratory results. None had renal dysfunction. The plasma total and free metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (MT) were analyzed and compared with age and gender-based reference percentiles established for 191 healthy pediatric controls by Franscini et al. (2015). Results: Follow up data up suggested a great variability in biomarker pattern with a broad spectrum of pathologies. Some tumors were still metabolically active although radiologically stable, which makes biomarkers interpretation challenging. Other patients still exhibited tumoral tissue without any metabolic activity. In a vast majority of cases, we observe normalisation of both metanephrines and catecholamines after treatment. At diagnosis, the combination of VMA and HVA urinary markers had a sensitivity of 90%. Plasma free MT had only 46% sensitivity with 0.1 nmol/l as cut-off. Plasma total MT and free NMN for NB diagnosis as single markers showed an 87% and 93% sensitivity respectively. Interestingly sensitivity increased up to 100% when plasma total MT and free NMN were combined. Conclusion and perspectives: In this retrospective observational design, our follow-up data underlies the broad clinical presentation of NB correlated with great variability of both catecholamines and metanephrines patterns. This underlies the need of considering the patient as a whole clinical and biological picture. The main outcome measure was 100% sensitivity for NB diagnosis with combined use of plasma total MT and free NMN in low to intermediate risk patients. In contrast, fMT seems not to be a satisfying parameter at diagnosis for low risk to intermediate risk specific NB disease. We confirmed better sensitivity of Franscini et al. partitioning by age and gender percentiles for plasma metanephrines as compared with the current reference limits. These promising results need further assessment and confirmation in a prospective large national multicentric study including low to high-risk NB patients.