scholarly journals Statistical Framework in Support of a Revised Children's Oncology Group Neuroblastoma Risk Classification System

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Arlene Naranjo ◽  
Meredith S. Irwin ◽  
Michael D. Hogarty ◽  
Susan L. Cohn ◽  
Julie R. Park ◽  
...  
Keyword(s):  
Classification System ◽  
Recursive Partitioning ◽  
Diagnostic Category ◽  
Staging System ◽  
Risk Classification ◽  
Imaging Data ◽  
Oncology Group ◽  
Clinical Validity ◽  
International Consensus ◽  
Str Analysis

Purpose The International Neuroblastoma Risk Group (INRG) Staging System (INRGSS) was developed through international consensus to provide a presurgical staging system that uses clinical and imaging data at diagnosis. A revised Children's Oncology Group (COG) neuroblastoma (NB) risk classification system is needed to incorporate the INRGSS and within the context of modern therapy. Herein, we provide statistical support for the clinical validity of a revised COG risk classification system. Patients and Methods Nine factors were tested for potential statistical and clinical significance in 4,569 patients diagnosed with NB who were enrolled in the COG biology/banking study ANBL00B1 (2006-2016). Recursive partitioning was performed to create a survival-tree regression (STR) analysis of event-free survival (EFS), generating a split by selecting the strongest prognostic factor among those that were statistically significant. The least absolute shrinkage and selection operator (LASSO) was applied to obtain the most parsimonious model for EFS. COG patients were risk classified using STR, LASSO, and per the 2009 INRG classification (generated using an STR analysis of INRG data). Results were descriptively compared among the three classification approaches. Results The 3-year EFS and overall survival (± SE) were 72.9% ± 0.9% and 84.5% ± 0.7%, respectively (N = 4,569). In each approach, the most statistically and clinically significant factors were diagnostic category (eg, NB, ganglioneuroblastoma), INRGSS, MYCN status, International Neuroblastoma Pathology Classification, ploidy, and 1p/11q status. The results of the STR analysis were more concordant with those of the INRG classification system than with LASSO, although both methods showed moderate agreement with the INRG system. Conclusion These analyses provide a framework to develop a new COG risk classification incorporating the INRGSS. There is statistical evidence to support the clinical validity of each of the three classifications: STR, LASSO, and INRG.

scholarly journals Age, Diagnostic Category, Tumor Grade, and Mitosis-Karyorrhexis Index Are Independently Prognostic in Neuroblastoma: An INRG Project

2020 ◽  
Vol 38 (17) ◽  
pp. 1906-1918 ◽  
Author(s):  
Elizabeth Sokol ◽  
Ami V. Desai ◽  
Mark A. Applebaum ◽  
Dominique Valteau-Couanet ◽  
Julie R. Park ◽  
...  
Keyword(s):  
Risk Group ◽  
Recursive Partitioning ◽  
Diagnostic Category ◽  
Staging System ◽  
Tumor Grade ◽  
Risk Classification ◽  
Event Free Survival ◽  
Cox Models ◽  
Free Survival ◽  
The Individual

PURPOSE The Children’s Oncology Group (COG) stratifies the treatment of patients with neuroblastoma on the basis of a combination of biomarkers that include age and tumor histology classified by age-linked International Neuroblastoma Pathology Classification (INPC) criteria. By definition, this leads to a duplication of the prognostic contribution of age. The individual histologic features underlying the INPC have prognostic strength and are incorporated in the International Neuroblastoma Risk Group classification schema. Here, we analyzed data in the International Neuroblastoma Risk Group Data Commons to validate the prognostic strength of the underlying INPC criteria and to determine whether a risk classification devoid of the confounding of age and INPC criteria will identify new prognostic subgroups. PATIENTS AND METHODS Event-free survival of patients diagnosed between 1990 and 2002 (cohort 1; n = 10,104) and between 2003 and 2016 (cohort 2; n = 8,761) was analyzed. Recursive partitioning with univariate Cox models of event-free survival (“survival tree regression”) was performed using (1) individual INPC criteria (age at diagnosis, histologic category, mitosis-karyorrhexis index (MKI), grade of differentiation) and (2) factors in (1) plus other COG-risk biomarkers (International Neuroblastoma Staging System [INSS] stage, MYCN status, ploidy). RESULTS The independent prognostic ability of age, histologic category, MKI, and grade were validated. Four histologic prognostic groups were identified (< 18 months with low v high MKI, and ≥ 18 months with differentiating v undifferentiated/poorly differentiating tumors). Compared with survival trees generated with established COG risk criteria, an additional prognostic subgroup was identified and validated when individual histologic features were analyzed in lieu of INPC. CONCLUSION Replacing INPC with individual histologic features in the COG risk classification will eliminate confounding, facilitate international harmonization of risk classification, and provide a schema for more precise prognostication and refined therapeutic approaches.

The Pediatric Oncology Group experience with the international staging system criteria for neuroblastoma. Member Institutions of the Pediatric Oncology Group.

1994 ◽  
Vol 12 (11) ◽  
pp. 2378-2381 ◽  
Author(s):  
R P Castleberry ◽  
J J Shuster ◽  
E I Smith
Keyword(s):  
Lymph Node ◽  
Pediatric Oncology ◽  
Regional Lymph Node ◽  
Staging System ◽  
Distant Metastases ◽  
Lymph Node Involvement ◽  
Oncology Group ◽  
International Consensus ◽  
Age Related ◽  
Pediatric Oncology Group

PURPOSE An international consensus on the criteria for surgicopathologic staging (INSS) of patients with neuroblastoma has been published, but has not been validated. A retrospective study was conducted to assess if the INSS definitions identified prognostic subsets of patients with neuroblastoma. PATIENTS AND METHODS The initial operative and pathology reports were reviewed from 675 patients on Pediatric Oncology Group (POG) #8104, a stage- and age-related treatment study that used the POG surgicopathologic staging system. RESULTS Of 596 eligible cases, there was concordance between the POG and INSS stages for the 193 patients with localized, resected disease (POG stage A), the 202 with distant metastases, the 51 with POG stage Ds (IVs) tumors, and 40 of the cases with grossly unresected, localized tumor without lymph node involvement (POG stage B). Of the remaining 19 patients with POG stage B tumors, five were INSS stage 2B and 14 INSS stage 3. All of the 91 cases with nonadherent, regional lymph node metastases (POG stage C) conformed to the definitions for INSS stage 2B (n = 42) or 3 (n = 49). In infants, there was no difference in event-free survival (EFS) among INSS stages 2A, 2B, or 3. In contrast, older children with INSS stage 3 disease had inferior EFS compared with INSS stage 2A or 2B tumors. CONCLUSION We conclude the following: (1) the INSS identifies distinct patient subsets, particularly in children; (2) infants remain a favorable group, regardless of INSS/POG stage; and (3) the INSS deserves further prospective study especially in the light of recent biologic prognostic variables.

Update on the development of the international neuroblastoma risk group (INRG) classification schema

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9503-9503 ◽  
Author(s):  
S. L. Cohn ◽  
W. B. London ◽  
T. Monclair ◽  
K. K. Matthay ◽  
P. F. Ambros ◽  
...  
Keyword(s):  
Classification System ◽  
Risk Group ◽  
Diagnostic Category ◽  
Treatment Strategies ◽  
Staging System ◽  
Mycn Amplification ◽  
Tumor Differentiation ◽  
Treatment Groups ◽  
Ultra High Risk ◽  
Pre Treatment

9503 Background: Modern treatment strategies for neuroblastoma (NB) are tailored according to patient risk. However, it is not currently possible to compare the results of clinical studies conducted around the globe because the criteria used to define risk are not uniform. A committee of international investigators with expertise in NB have worked during the past 2 years to develop a uniform International NB Risk Group (INRG) Classification System for pre-treatment stratification. Methods: Investigators from North America and Australia (COG); Europe (SIOPEN and Germany), and Japan collated data on 8,800 children with NB diagnosed between 1990 and 2002. Survival tree regression analyses tested 13 potential prognostic factors. Tumor differentiation, MKI, and diagnostic category were evaluated individually in lieu of the International NB Pathology Classification (INPC) system to determine if these histologic features had prognostic value independent from age. To stage patients at the time of diagnosis prior to surgery, a new staging system was developed (INRGSS) based on the presence or absence of image-defined risk factors (IDRFs) and metastases. Results: Since statistical analyses demonstrated support for an optimal age cut- off between 14–19 months, 18 months was selected. In addition to age, stage, MYCN amplification, tumor differentiation, ploidy, and genetic aberrations of 11q were found to be the most highly prognostically significant factors. These clinical and biological factors were combined to define 15 INRG pre-treatment groups. Patients with low- (3 groups), intermediate- (4 groups), high- (4 groups), or ultra-high-risk NB (4 groups) had EFS of ≥85%, >70–85%, >50–70%, or <50%, respectively. Conclusion: International collaborative studies in NB will be greatly facilitated by the INRG classification system which will allow comparisons of different risk-based therapeutic approaches in homogeneous patient cohorts. No significant financial relationships to disclose.

Revised Neuroblastoma Risk Classification System: A Report From the Children's Oncology Group

2021 ◽  
pp. JCO.21.00278
Author(s):  
Meredith S. Irwin ◽  
Arlene Naranjo ◽  
Fan F. Zhang ◽  
Susan L. Cohn ◽  
Wendy B. London ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
Staging System ◽  
Risk Classification ◽  
Intermediate Risk ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Pathology Classification

PURPOSE Treatment planning for children with neuroblastoma requires accurate assessment of prognosis. The most recent Children's Oncology Group (COG) risk classification system used tumor stage as defined by the International Neuroblastoma Staging System. Here, we validate a revised classifier using the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporate segmental chromosome aberrations (SCA) as an additional genomic biomarker. METHODS Newly diagnosed patients enrolled on the COG neuroblastoma biology study ANBL00B1 between 2007 and 2017 with known age, International Neuroblastoma Staging System, and INRGSS stage were identified (N = 4,832). Tumor MYCN status, ploidy, SCA status (1p and 11q), and International Neuroblastoma Pathology Classification histology were determined centrally. Survival analyses were performed for combinations of prognostic factors used in COG risk classification according to the prior version 1, and to validate a revised algorithm (version 2). RESULTS Most patients with locoregional tumors had excellent outcomes except for those with image-defined risk factors (INRGSS L2) with MYCN amplification (5-year event-free survival and overall survival: 76.3% ± 5.8% and 79.9% ± 5.5%, respectively) or patients age ≥ 18 months with L2 MYCN nonamplified tumors with unfavorable International Neuroblastoma Pathology Classification histology (72.7% ± 5.4% and 82.4% ± 4.6%), which includes the majority of L2 patients with SCA. For patients with stage M (metastatic) and MS (metastatic, special) disease, genomic biomarkers affected risk group assignment for those < 12 months ( MYCN) or 12-18 months ( MYCN, histology, ploidy, and SCA) of age. In a retrospective analysis of patient outcome, the 5-year event-free survival and overall survival using COG version 1 were low-risk: 89.4% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 86.1% ± 1.3% and 94.9% ± 0.8%; high-risk: 50.8% ± 1.4% and 61.9% ± 1.3%; and using COG version 2 were low-risk: 90.7% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 85.1% ± 1.4% and 95.8% ± 0.8%; high-risk: 51.2% ± 1.4% and 62.5% ± 1.3%, respectively. CONCLUSION A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates SCAs has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.

scholarly journals Tailoring Therapy for Children With Neuroblastoma on the Basis of Risk Group Classification: Past, Present, and Future

2020 ◽  
pp. 895-905
Author(s):  
Wayne H. Liang ◽  
Sara M. Federico ◽  
Wendy B. London ◽  
Arlene Naranjo ◽  
Meredith S. Irwin ◽  
...  
Keyword(s):  
Task Force ◽  
Risk Group ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Staging System ◽  
Risk Classification ◽  
Disease Stage ◽  
Learning Tools ◽  
Oncology Group ◽  
Frontline Treatment

For children with neuroblastoma, the likelihood of cure varies widely according to age at diagnosis, disease stage, and tumor biology. Treatments are tailored for children with this clinically heterogeneous malignancy on the basis of a combination of markers that are predictive of risk of relapse and death. Sequential risk-based, cooperative-group clinical trials conducted during the past 4 decades have led to improved outcome for children with neuroblastoma. Increasingly accurate risk classification and refinements in treatment stratification strategies have been achieved with the more recent discovery of robust genomic and molecular biomarkers. In this review, we discuss the history of neuroblastoma risk classification in North America and Europe and highlight efforts by the International Neuroblastoma Risk Group (INRG) Task Force to develop a consensus approach for pretreatment stratification using seven risk criteria including an image-based staging system—the INRG Staging System. We also update readers on the current Children’s Oncology Group risk classifier and outline plans for the development of a revised 2021 Children’s Oncology Group classifier that will incorporate INRG Staging System criteria to facilitate harmonization of risk-based frontline treatment strategies conducted around the globe. In addition, we discuss new approaches to establish increasingly robust, future risk classification algorithms that will further refine treatment stratification using machine learning tools and expanded data from electronic health records and the INRG Data Commons.

scholarly journals The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force Report

2009 ◽  
Vol 27 (2) ◽  
pp. 298-303 ◽  
Author(s):  
Tom Monclair ◽  
Garrett M. Brodeur ◽  
Peter F. Ambros ◽  
Hervé J. Brisse ◽  
Giovanni Cecchetto ◽  
...  
Keyword(s):  
Classification System ◽  
Task Force ◽  
Risk Group ◽  
Staging System ◽  
Risk Classification ◽  
Clinical Staging ◽  
Task Force Report ◽  
Clinical Criteria ◽  
Stage 1 ◽  
The Impact

Purpose 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. Methods 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. Results 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). Conclusion 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.

A revised Children's Oncology Group (COG) neuroblastoma risk classification system: Report from the COG biology study ANBL00B1.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10012-10012
Author(s):  
Meredith Irwin ◽  
Arlene Naranjo ◽  
Susan Lerner Cohn ◽  
Wendy B London ◽  
Julie M Gastier-Foster ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prognostic Factors ◽  
Classification System ◽  
Risk Group ◽  
Staging System ◽  
Risk Classification ◽  
Classification Systems ◽  
Pre Treatment ◽  
Modern Era ◽  
Clinical Trial Information

10012 Background: The COG risk classification system previously used the International Neuroblastoma Staging System (INSS). The pre-treatment INRG staging system (INRGSS) has been adopted internationally, requiring integration of INRGSS with known prognostic biological and clinical characteristics to evaluate outcomes and assess whether this incorporation will require revision to the established COG risk classifier. Methods: 4,037 newly diagnosed neuroblastoma patients were enrolled on COG ANBL00B1 between 2006-2014. Staging per the INSS and INRGSS was determined. Tumor biological and histologic features, including MYCN status [amplified (A) versus not amplified (NA)], ploidy, histology, and segmental chromosome aberrations (SCA) including 1p and 11q LOH, were assessed centrally. Survival analyses were performed to identify independent prognostic factors and to calculate event-free and overall survival (EFS, OS) for combinations of variables used to determine risk group assignments according to COG and INRG classification templates. Results: Using the original COG risk classifier 1,309 low (LR), 992 intermediate (IR) and 1,736 high-risk (HR) patients were identified with 5-year EFS of 91.4±2.1%, 84.3±2.9%, 45.2±3.1%, and OS of 98.1±1.0%, 94.0±1.9%, 54.1±3.0%, respectively. Outcomes based on combinations of clinical and biological prognostic factors were determined and compared for subsets of patients according to the COG (version1) and INRG risk classification systems to develop a revised COG risk classifier that incorporates the INRGSS (version 2, subset shown in table). Conclusions: Use of INRGSS requires a revision to the COG risk classifier. By combining INRGSS and presence of SCA together with age, MYCN status, ploidy, and histology to determine outcome of patients treated with modern era therapies, we developed a revised risk classification system to inform therapy and COG clinical trial eligibility. Clinical trial information: NCT00904241. [Table: see text]

scholarly journals Percepção de enfermeiros sobre utilização do protocolo do sistema de classificação de risco manchester/ Nurses’ perception on the use of the manchester risk classification system protocol

2015 ◽  
Vol 14 (2) ◽  
pp. 1004 ◽  
Author(s):  
Marcia Luciane da Silva Bohn ◽  
Maria Alice Dias da Silva Lima ◽  
Carmen Lúcia Mottin Duro ◽  
Kelly Piacheski de Abreu
Keyword(s):  
Classification System ◽  
Risk Classification
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