The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report

University of Cologne, Köln, North Rhine-Westphalia, Germany
Journal of Clinical Oncology (Impact Factor: 18.43). 01/2009; 27(2):298-303. DOI: 10.1200/JCO.2008.16.6876
Source: PubMed


The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system.
To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known.
In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010).
Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.

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    • "2012). Features like age of the patient at diagnosis, stage of the disease, and nonrandom chromosomal aberrations are well-established parameters for stratification of risk and treatment as well as for predicting the disease outcome in patients (Cohn et al., 2009; Monclair et al., 2009). Neuroblastoma patients with nonrandom chromosomal alterations MNA (MYCN amplification )/1p (shorter arm of the chromosome 1) deletion/17q (longer arm of the chromosome 17) gain (seen in 20% of patients) or 11q deletion (11q-) /17q gain (seen in 30% of patients) are often associated with high-risk tumors and an unfavorable outcome. "
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    ABSTRACT: Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to NBAT-1 differential expression. Loss of NBAT-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. NBAT-1 loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors. Copyright © 2014 Elsevier Inc. All rights reserved.
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    • "(2) The high-risk group, comprising all MYCN-amplified NB, regardless of stage and age of the child, plus non-MYCN-amplified disseminated NB for children older than 18 months, usually very aggressive tumors that more frequently lead to death (8). However, relapse for low-risk patients constitutes a current concern (9), hence the International Neuroblastoma Risk Group Staging System (INRGSS) has recently established a new classification based on clinical criteria and image-defined risk factors (10). It distinguishes localized stages L1 and L2, and stages M and MS as disseminated forms. "
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    ABSTRACT: Neuroblastoma (NB), accounting for 10% of childhood cancers, exhibits aberrant cell-surface glycosylation patterns. There is evidence that changes in glycolipids and protein glycosylation pathways are associated to NB biological behavior. Polysialic acid (PSA) interferes with cellular adhesion, and correlates with NB progression and poor prognosis, as well as the expression of sialyltransferase STX, the key enzyme responsible for PSA synthesis. Galectin-1 and gangliosides, overexpressed and actively shedded by tumor cells, can modulate normal cells present in the tumor microenvironment, favoring angiogenesis and immunological escape. Different glycosyltransferases are emerging as tumor markers and potential molecular targets. Immunotherapy targeting disialoganglioside GD2 rises as an important treatment option. One anti-GD2 antibody (ch14.18), combined with IL-2 and GM-CSF, significantly improves survival for high-risk NB patients. This review summarizes our current knowledge on NB glycobiology, highlighting the molecular basis by which carbohydrates and protein-carbohydrate interactions impact on biological behavior and patient clinical outcome.
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    • "However, infants below 18 months old constituted about 25% of the patients, which is much smaller than what reported by some other investigators (3,6,14,15). Instead, the majority of our patients were in the age-range between 18 and 60 months, which is already considered as the high risk group according to the International Neuroblastoma Risk Group (INRG) task force report (16,17).Similar to other reports (3,5-9,11,18,19), adrenal gland was the most frequent site of primary disease. "
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    ABSTRACT: Background Neuroblastoma is the third most common malignancy in children with a very heterogeneous feature. In this study, the epidemiological and clinical characteristics of children with neuroblastoma treated in a referral oncology hospital in Shiraz, Southern Iran, were investigated. Material and method In this historical cohort study, the medical files of 36 children under 18 years old with neuroblastoma were reviewed, who were admitted to Amir Oncology Hospital in Shiraz, Iran from 2006 to 2013. Overall survival and event free survival (EFS) curves were demonstrated by Kaplan Meier methods. Also the effects of demographic and clinical characteristics of the patients on survival were evaluated by Cox regression model. Results The median age of diagnosis was 30 months (age range: from 4 to144 months), with M/F ratio of 63.9%. Over 70% of the patients had stage 4 of neuroblastoma at their initial presentations. Adrenal gland comprised 72.2% of the primary tumor site. The most common presenting symptoms were gastrointestinal and constitutional symptoms. The mean overall survival and EFS were 30.75 and 20.56 months, respectively. Among the different variables analyzed, only liver metastasis had an adverse effect on EFS (p=0.025 Hazard ratios 2.83, CI: 1.14-7.02). Conclusion This study revealed that the majority of children suffering from neuroblastoma in our center are high stage with disseminated disease at the time of detection. It also warns us about an urgent necessity for holding a re-educational program for general practitioners and pediatricians to review the warning signs of common pediatric cancers such as neuroblastoma.
    Full-text · Article · Jul 2014
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