Evolving significance of prognostic markers associated with treatment improvement in patients with Stage 4 neuroblastoma

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Abstract
BACKGROUND: With recent improvements in the treatment and outcome of patients with neuroblastoma (NB), the authors reassessed the prognostic importance of clinical and biologic markers in patients with Stage 4 NB who were treated at the Memorial Sloan‐Kettering Cancer Center (MSKCC).METHODS: The authors analyzed 84 patients with Stage 4 NB who were treated on the N5, N6, or N7 protocols at MSKCC from 1987 to 1999. The impact on survival of clinical factors (age, serum ferritin, and lactate dehydrogenase [LDH] levels), histopathology (International Neuroblastoma Pathology Classification [INPC]), and tumor biologic markers (MYCN; ploidy; loss of heterozygosity [LOH] at 1p36, 1p22, 11q23, 14q12–q32, 9p21, and 19q13; and gain at 17q) were analyzed in univariate and multivariate models.RESULTS: Forty‐six of 84 patients were alive at the time of this report (55%), with a median follow‐up of 41 months from the time of diagnosis. In the univariate analysis, there was no prognostic impact on survival by age, serum ferritin and LDH levels,MYCN, 1p36 LOH, 14q32 LOH, or 17q gain. LOH at 11q23 was associated significantly with superior progression free survival (P= 0.04) and survival (P= 0.04) in the univariate analysis. In the multivariate analysis, it was found that 11q23 status was the most significant variable associated with overall survival (hazard ratio, 0.50; 95% confidence interval, 0.26–0.99). LOH at 11q23 and LOH at 1p22 were highly correlated (P= 0.02). It was found that 11q23 status and INPC score were the most significant variables associated with progression free survival.CONCLUSIONS: Because patient survival improves with more effective therapy, traditional prognostic markers, such as age,MYCNamplification, and elevated serum LDH levels, have become less important for patients with Stage 4 NB. In the current study, less common chromosomal abnormalities (LOH at 1p22 and 11q23) appeared to assume new importance. Cancer 2002;94:2756–65. © 2002 American Cancer Society.DOI 10.1002/cncr.10548