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.

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 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 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 Significance of MYCN Amplification in International Neuroblastoma Staging System Stage 1 and 2 Neuroblastoma: A Report From the International Neuroblastoma Risk Group Database

2009 ◽  
Vol 27 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Rochelle Bagatell ◽  
Maja Beck-Popovic ◽  
Wendy B. London ◽  
Yang Zhang ◽  
Andrew D.J. Pearson ◽  
...  
Keyword(s):  
Risk Group ◽  
Prognostic Significance ◽  
Staging System ◽  
Moderate Intensity ◽  
Mycn Amplification ◽  
Localized Neuroblastoma ◽  
International Neuroblastoma Staging System ◽  
Stage 1 ◽  
Additional Therapy

Purpose Treatment of patients with localized neuroblastoma with unfavorable biologic features is controversial. To evaluate the outcome of children with low-stage MYCN-amplified neuroblastoma and develop a rational treatment strategy, data from the International Neuroblastoma Risk Group (INRG) database were analyzed. Patients and Methods The database is comprised of 8,800 patients. Of these, 2,660 patients (30%) had low-stage (International Neuroblastoma Staging System stages 1 and 2) neuroblastoma, known MYCN status, and available follow-up data. Eighty-seven of these patients (3%) had MYCN amplified tumors. Results Patients with MYCN-amplified, low-stage tumors had less favorable event-free survival (EFS) and overall survival (OS) than did patients with nonamplified tumors (53% ± 8% and 72% ± 7% v 90% ± 1% and 98% ± 1%, respectively). EFS and OS were statistically significantly higher for patients whose tumors were hyperdiploid rather than diploid (EFS, 82% ± 20% v 37% ± 21%; P = .0069; OS, 94% ± 11% v 54% ± 15%; P = .0056, respectively). No other variable had prognostic significance. Initial treatment consisted of surgery alone for 29 (33%) of 87 patients. Details of additional therapy were unknown for 14 patients. Twenty-two patients (25%) underwent surgery and moderate-intensity chemotherapy; another 22 underwent surgery, intensive chemotherapy, and radiation therapy. Nine of the latter 22 underwent stem cell transplantation. Survival in patients who received transplantation did not differ from survival in those who did not receive transplantation. Conclusion Among patients with low-stage, MYCN-amplified neuroblastoma, outcomes of patients with hyperdiploid tumors were statistically, significantly better than those with diploid tumors. The data suggest that tumor cell ploidy could potentially be used to identify candidates for reductions in therapy. Further study of MYCN-amplified, low-stage neuroblastoma is warranted.

Hepatoblastoma: Review of Pathology, Diagnosis and Modern Treatment Strategies

2020 ◽  
Vol 16 (4) ◽  
pp. 276-291
Author(s):  
Adil A. Abbas ◽  
Alaa M.N. Samkari ◽  
Abeer S. Almehdar
Keyword(s):  
Surgical Techniques ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Staging System ◽  
The United States ◽  
Surgical Approaches ◽  
Beta Hcg ◽  
Individualized Approach ◽  
Pre Treatment ◽  
Consensus Classification

Hepatoblastoma (HB) is the most common primary malignant hepatic tumor of childhood and, occurring predominantly in the first two years of life. Approximately 100 cases are diagnosed every year in the United States of America. The management of HB has changed markedly over the last three decades. Alfa feto protein (AFP) and beta human chorionic gonadotrophin (beta HCG) are the main tumor markers and are markers for diagnosis and follow up. International collaborative efforts have led to the implementation of the Pre - Treatment Extent of the Disease PRETEXT staging system consensus classification to assess upfront resectability. Complete surgical resection plays a key role in successful management. Overall, outcomes have greatly improved over the past decades mainly because of advances in chemotherapy (CTR) agents and administration protocols, newer surgical approaches and liver transplantation (LT). Targeted medications towards the newly discovered &#946;-catenin and Wnt genetic pathways in tumor cells may soon become an option for treatment. The current disease free survival (DFS) rates are approaching 85%. For the 25% of patients with metastasis at presentation, the overall survival (OS) remains poor. A more individualized approach to treating the heterogeneous spectrum of HB may become the basis of successful treatment in complex cases. Newer medications and surgical techniques are being exploited. Here we present a comprehensive review of the recent advances in the management of HB. A wide literature search was made using internet search engines such as PubMed and Google scholar. More than 100 articles were reviewed and the information extrapolated was arranged to produce this review.

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

2009 ◽  
Vol 27 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Susan L. Cohn ◽  
Andrew D.J. Pearson ◽  
Wendy B. London ◽  
Tom Monclair ◽  
Peter F. Ambros ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pediatric Oncology ◽  
Classification System ◽  
Risk Group ◽  
Prognostic Significance ◽  
Staging System ◽  
Low Risk ◽  
Task Force Report ◽  
Clinical Criteria ◽  
The World

Purpose Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Patients and Methods The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Results Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to ≤ 85%, ≥ 50% to ≤ 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. Conclusion By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.

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.

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 new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels.

1989 ◽  
Vol 7 (10) ◽  
pp. 1518-1527 ◽  
Author(s):  
F Swan ◽  
W S Velasquez ◽  
S Tucker ◽  
J R Redman ◽  
M A Rodriguez ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Risk Group ◽  
Treatment Protocol ◽  
Treatment Strategies ◽  
Staging System ◽  
Large Cell ◽  
High Risk Group ◽  
Rational Approach ◽  
Beta 2 ◽  
Beta 2 Microglobulin

We report results of our investigation of prognostic factors for patients with large-cell lymphoma who were entered on the same treatment protocol and who had known pretreatment serum beta 2-microglobulin (beta 2M) and lactate dehydrogenase (LDH) levels. beta 2M and LDH levels were the most significant and independent variables for predicting time to treatment failure (TTF) and survival. The serum level of beta 2M correlated with tumor burden. These two serum markers defined three significantly different prognostic groups. All 27 patients in the low-risk group remain alive and in remission; in contrast, 22 of the 27 patients (81%) in the high-risk group have failed treatment, and only seven (26%) remain alive. In comparison with the Ann Arbor staging system, serum levels of beta 2M and LDH may provide a more precise system for defining risk groups and thereby allow a more rational approach to the development and analysis of treatment strategies.

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