Significance of tumor biology compared to metastatic pattern (INSS 4 versus 4s) and age for prognosis of neuroblastoma less than 18 months of age

Abstract

10010 Background: Neuroblastoma is a heterogeneous disease with variability in outcome among different risk groups. Historically, INSS stage 4s neuroblastoma (age less than 12 months, stage 1 or 2 primary tumor with metastases limited to liver, skin and bone marrow) has a more favorable outcome than infant stage 4 disease. The aim was to determine if metastatic pattern (4 vs 4s) predicted favorable prognosis in infants < 12 months or in toddlers aged 12–18 months when stratifying by biology. Methods: Outcome was analyzed by log rank tests and Cox models for 656 infants with stage 4s neuroblastoma and 1,019 stage 4 patients < 18 months of age in the International Neuroblastoma Risk Group database (n=8,800). Prognostic factors (tumor ploidy, histology, grade, MKI, LDH, MYCN, 11q, 1p, primary site) were tested for association with age/stage subgroups (Fisher's exact test) and in Cox models. Results: MYCNamplification, 1p aberration, diploidy, and high MKI and LDH were more frequent in infant stage 4 than infant 4s tumors. The incidence of unfavorable biology was higher in toddlers aged 12–18 months, but did not differ with stage 4 vs. 4s pattern. EFS was significantly better for infants <12 months with stage 4s than stage 4 (p=0.0004). EFS was similar for toddlers 12–18 months for stage 4 vs. 4s pattern (p=0.3893). Within the 717 patients with 4s pattern of metastases, age 12–18 months had worse EFS than <12 months (p<0.0001). After adjustment for age in 6 separate models, MYCN, 11q, 1p, MKI, and LDH were statistically significant prognostic factors. Although treatment regimens differed, EFS was similar for <12 months vs. 12–18 months for MYCN not amplified patients in both 4S pattern (p=0.8469) and stage 4 (p=0.3783). Conclusions: For patients with MYCN not amplified tumors, outcome for patients 12–18 months is similar to those <12 months regardless of the pattern of metastases. Tumor biology is more critical than metastatic pattern for prognosis of patients aged 12–18 months with stage 4 neuroblastoma. [Table: see text] No significant financial relationships to disclose.