Catecholamine metabolites and their correlations with biological and clinical features in patients with neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in childhood. Besides
pathology (diagnostic golden standard), urinary catecholamines (VMA and HVA)
are measured as part of the diagnostic work-up and monitoring response to
therapy/follow-up. After the diagnosis has been established, the patient is
allocated to a risk-group and treated accordingly. Current risk-group
stratification (low-, intermediate- and high risk) is based on clinical
parameters (metastatic disease), pathological and genetic factors, such as MYCN
amplification. In all risk groups, patients with the same risk assessment, and
thus receiving the same treatment, can have markedly different outcomes.
Therefore, additional markers that can distinguish low and high risk disease
more accurately are needed. Furthermore, these markers might also assist in
therapy monitoring and early detection of relapse/progression.

In 90-95% of neuroblastoma patients, the urinary concentrations of
catecholamine metabolites are strongly elevated and provide an important
non-invasive diagnostic tool for diagnosis, during treatment and at follow up.
Our retrospective study showed that implementation of a panel of 8
catecholamines, instead of only VMA and HVA, improves diagnostic sensitivity by
10%. Furthermore, 1 of the catecholamines also correlated with high-risk
disease and thus with clinical outcome. For this reason, in this project we
intend to prospectively validate these findings in order to improve standard
care (diagnostics and risk-group allocation).

Main aim:
Identify the optimal urinary catecholamine metabolites panel for neuroblastoma
diagnostics.

Sub-aims:
1. Investigate whether catecholamine metabolites can also be linked to
prognosis and thus assist in risk assessment.
2. Investigate whether catecholamine metabolites can be used for monitoring
response to therapy and possible progression/relapse
3. Determine which medium (urine or plasma) is the most accurate for
catecholamine metabolites measurement.

Prospective study of catecholamine metabolites (dopamine, 3-methoxytyramine,
norepinephrine, normetanephrine, epinephrine, metanephrine, HVA and VMA) in
urine of every newly diagnosed neuroblastoma patient. Measurements will be done
at certain points during the clinical course (e.g. at diagnosis, before and
after surgery, etc.).

Furthermore, a pilot-study will be done based on 20 patients. In this study,
the urinary catecholamine metabolites will be compared to their corresponding
plasma levels. If the plasma catecholamine will be as sensitive/more sensitive
than the urine catecholamine, the study cohort will be increased to the
complete urine cohort.

Urine: no burden, it's part of the standard diagnostics (only the metabolites
panel is broader)
Plasma: blood will be collected as part of routine diagnostics. During these
moments, when possible, 1 additional will be taken.