INDOLENT COURSE OF ADVANCED NEUROBLASTOMA IN CHILDREN OLDER THAN 6 YEARS AT DIAGNOSIS

Background. An early observation suggests that children older than 6 y ears of age at diagnosis of neuroblastoma constitute a favorable progn ostic group. Methods. Kaplan-Meier plots of survival of all such patie nts diagnosed at the Children's Hospital of Pittsburgh 1975-1992 were compared with curves of concurrently treated patients with Stage IV di sease who were 16 years of age at diagnosis (''younger patients''). Kn own prognostic features, including stage and primary site of disease, pattern of metastases, histopathology, MYCN gene amplification, and ur inary catecholamine metabolite ratios, were reviewed. Results. Of 17 c hildren diagnosed after the age of 6 years (''older patients''), 13 pa tients had Evans' Stage IV disease and 4 had Stage III disease. The me dian survival was 3.24 years (range, 0.63-15.04 years) for the entire cohort and 3.07 years for those children with Stage IV disease. This c ompared with a median survival of 1.05 years in 34 concurrent younger patients (P < 0.01). In most cases, disease in these older patients wa s characterized by a short-lived complete or partial remission followe d by aggressive recurrent disease that was partially and only transien tly chemo- or radiosensitive. Only 3 patients (2 with Stage IV disease ) are in continuous complete remission at 3, 5 10/12, and 14 1/2 years from diagnosis. Although poor prognostic factors were common, includi ng the presence of bony metastases (12/17), biopsy material from pretr eatment tumor specimens demonstrated a single MYCN gene copy number in all patients and favorable histology in 15 of 16 samples. Conclusion. Older children with neuroblastoma have a more indolent course than do younger patients, a finding that appears to be related to favorable h istology and the absence of MYCN amplification. Examination of larger numbers of such patients from cooperative groups should lead to a bett er understanding of what appears to be a subset of pediatric patients with neuroblastoma who may benefit from specifically tailored treatmen t protocols.