Prognostic Value of the Stage 4S Metastatic Pattern and Tumor Biology in Patients With Metastatic Neuroblastoma Diagnosed Between Birth and 18 Months of Age

Abstract

A B S T R A C T PurposePatients with neuroblastoma younger than 12 months of age with a 4S pattern of disease (metastases limited to liver, skin, bone marrow) have better outcomes than infants with stage 4 disease. The new International Neuroblastoma Risk Group (INRG) staging system extends age to 18 months for the 4S pattern. Our aim was to determine which prognostic features could be used for optimal risk classification among patients younger than 18 months with metastatic disease. MethodsEvent-free survival (EFS) and overall survival were analyzed by log-rank tests, Cox models, and survival tree regression for 656 infants with stage 4S neuroblastoma younger than 12 months of age and 1,019 patients with stage 4 disease younger than 18 months of age in the INRG database. ResultsUnfavorable biologic features were more frequent in infants with stage 4 disease than in infants with 4S tumors and higher overall in those age 12 to 18 months (although not different for stage 4 v 4S pattern). EFS was significantly better for infants younger than 12 months with 4S pattern than with stage 4 disease (P Ͻ .01) but similar for toddlers age 12 to 18 months with stage 4 versus 4S pattern. Among 717 patients with stage 4S pattern, patients age 12 to 18 months had worse EFS than those age younger than 12 months (P Ͻ .01). MYCN, 11q, mitosis-karyorrhexis index (MKI), ploidy, and lactate dehydrogenase were independently statistically significant predictors of EFS and more highly predictive than age or metastatic pattern. MYCN, 11q, MKI, histology, and 1p were combined in a survival tree for improved risk stratification. ConclusionTumor biology is more critical than age or metastatic pattern for prognosis of patients age younger than 18 months with metastatic neuroblastoma and should be considered for risk stratification.

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

“…It is widely accepted that near-triploid cells are characteristic of low-risk Neuroblastoma, which indicates that supernumerary whole chromosomes are a feature of non-aggressive tumors [15, 17]. Recently, we performed a survey of 2994 cases, which included all stages of Neuroblastoma, and we confirmed that aneuploidy is more frequent in tumors of patients younger than 18 months of age with stage 1, 2, 3, or 4 disease compared with older patients (Fig.…”

Image‐defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra‐operative risk factors and the completeness of resection

“…This finding could be related to a more undifferentiated histology of M tumors but also to the preoperative chemotherapy regimens intended for high-risk (HR) patients that might have had a better impact on IDRFs than regimens designed for non HR patients. In patients with Ms disease, the decline in IDRFs might be explained both by the efficacy of chemotherapy and by a favorable tumor biology [19][20][21]. Interestingly, we observed more tumors with MYCN amplification in the group of tumors that lost IDRFs than in the group of tumors that did not lose any IDRF.…”

Striking dichotomy in outcome of MYCN‐amplified neuroblastoma in the contemporary era

“…Thus, in a 1999–2004 multicenter study of MYCN (+) infants, EFS/OS rates at only 2 years were 29%/30% for all stages (2-year OS was 20% for stage 4); 19 reviews of a 1990–2002 international experience found MYCN (+) stage 4 and 4S patients <18 months old to have 5-year EFS/OS rates of 28%/34% 45 and MYCN (+) stage 4 patients >18 months old to have 5-year EFS/OS rates of <25%; 16 and a 1991–1996 group-wide study of MYCN (+) stage 3 (all ages) yielded 5-year EFS/OS rates of 25%/27%. 11 …”