The catecholamine metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) were assayed in initial urine specimens of 288 patients with neuroblastoma and related tumors of neural crest origin (NCT). The interrelationships between the excretion of these metabolites, age at diagnosis, stage of the disease, site of the primary tumor, and prognosis were examined. In addition, to permit comparison with a control group of hospitalized children, the excretion of these metabolites by patients with Wilms' tumor was also examined. VMA was excreted above the upper limits of controls by 204 (71%) of 288 NCT patients and HVA was excreted by 196 (75%) of 260 NCT patients for whom data were available. The VMA excretion of the younger NCT patients was significantly higher than was that of NCT patients older than 1 year. Patients in Stages IV and IV-S excreted VMA at levels significantly higher than did those in Stages I to III. There was no significant relationship of VMA and HVA excretion to the primary site of the tumor. With regard to prognosis, age, stage of the disease, and site of the primary tumor were each independently related to survival, as has been reported previously by others. The patients with extraadrenal abdominal tumors had the poorest prognosis followed by adrenal, thoracic, pelvic, and cervical tumors in increasing order of survival. When all NCT patients were considered, HVA and the VMA/HVA ratio were significantly related to survival, but VMA excretion was not. When data on the Stage IV patients were analyzed separately, there was no significant relationship between survival time and VMA or HVA excretion, but the VMA/HVA ratio was still significantly related to survival.
The findings reported here from 288 NCT patients support the evidence that the initial urinary excretion levels of VMA and HVA are of value as an aid in diagnosis of 75%, or more, of patients with neuroblastoma and related tumors. Moreover, we wish to emphasize that elevated levels of VMA and/or HVA in initial urine specimens permit a definitive diagnosis of a neural crest tumor even when histological data are lacking or are nonspecific.
The relationships between urinary VMA and HVA and prognosis suggest that there is a common factor between the catecholamine metabolism within the tumor cells and their malignancy as reflected by the survival of the patients. Further investigations will be necessary to elucidate these relationships.
Supported in part by USPHS Fellowship Grant CA55731 and Grant CA08726, also in part by Grant CH-105 from the American Cancer Society, New York, N. Y. Computer time was provided by the Computer Science Center, University of Maryland, College Park, Md.; by the Institut Gustave-Roussy, Villejuif, France; and by the Institut International de la Santé et de la Recherche Médicale, Paris, France.