Elevated plasma catecholamines in neuroblastoma patients are associated with positive therapeutic response to chemotherapy regimen containing arsenic trioxide

Abstract Introduction Neuroblastoma (NB), a pediatric malignancy arising from the developing sympathetic nervous system, is frequently characterized by the excessive production and secretion of catecholamines. At present, the predictive value of plasma catecholamine concentration for patient prognosis, as well as its application in guiding therapeutic interventions, has not been clearly confirmed. Therefore, we conducted an analysis of a panel of plasma catecholamine metabolites in children with stage 4 NB to reveal their potential clinical significance. Patients and methods This study retrospectively analyzed the data of 16 children with INSS stage 4 NB. All patients were enrolled in a clinical trial of arsenic trioxide (ATO) combined chemotherapy. Plasma catecholamine metabolites including dopamine (DA), 3-methoxytyramine (3-MT), norepinephrine (NE), epinephrine (E), normetanephrine (NMN), and metanephrine (MN), were measured at diagnosis and at the end of induction. Correlations between plasma catecholamine metabolites levels and clinical characteristics as well as treatment outcome were analyzed. Result Six patients (37.5%) had elevated plasma catecholamine levels. Among them, one child had both malignant hypertension and tachycardia, three children only suffered from tachycardia, and the remaining two children had no adrenergic symptoms. The plasma levels of DA and E were significantly associated with urine vanillylmandelic acid-to-creatinine ratio (VMA/Cr), serum neurone specific enolase (NSE) as well as tumor size. More patients with hypercatecholamines reach complete remission (CR) after ATO-based induction therapy compared with those without hypercatecholamines ( P = 0.036). The plasma DA level in CR group after induction therapy is significantly higher than that in non-CR (NCR) group ( P = 0.002). Patients with hypercatecholaminemia exhibited a trend toward improved overall survival (OS) and progression-free survival (PFS), but the differences were not statistically significant (OS, P = 0.577; PFS, P = 0.398). Conclusion Catecholamine secretion and metabolism are heterogeneous in NB patients, who are partially symptomatic. NB patients with elevated catecholamines in plasma, particularly those with increased DA levels, have more favorable response to chemotherapy regimen containing ATO. Further parallel-controlled study studies with expanded sample sizes and mechanistic investigations are warranted to validate these preliminary findings.