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


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A Master's thesis.
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Master (thesis) (master)
Evaluation rétrospective de la signification pronostique de la méthoxytyramine plasmatique dans le suivi d’enfants atteints de neuroblastome de risque bas et intermédiaire
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Université de Lausanne, Faculté de biologie et médecine
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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
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.
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05/09/2018 16:14
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08/09/2020 7:10
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