Statistical Framework in Support of a Revised Children's Oncology Group Neuroblastoma Risk Classification System - PubMed (original) (raw)
Statistical Framework in Support of a Revised Children's Oncology Group Neuroblastoma Risk Classification System
Arlene Naranjo et al. JCO Clin Cancer Inform. 2018 Dec.
Abstract
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.
Conflict of interest statement
Arlene Naranjo
No relationship to disclose
Meredith S. Irwin
No relationship to disclose
Michael D. Hogarty
No relationship to disclose
Susan L. Cohn
Stock and Other Ownership Interests: United Therapeutics, United Therapeutics (I), Varian Medical Systems (I), Vermillion, Resmed (I), Merck, Merck (I), Stryker, Stryker (I), Amgen, Amgen (I), Pfizer, Pfizer (I), Abbvie, Jazz Pharmaceuticals, Eli Lilly, Sanofi, Varex Imaging, Vermillion
Research Funding: United Therapeutics (Inst), Merck (Inst)
Julie R. Park
Honoraria: Bristol-Myers Squibb
Travel, Accommodations, Expenses: Roche
Wendy B. London
No relationship to disclose
Figures
Fig 1.
Relationship between the INSS and the INRGSS. IDRF, image-defined risk factor; INRGSS, International Neuroblastoma Risk Group Staging System; INSS, International Neuroblastoma Staging System; mIBG, metaiodobenzylguanidine.
Fig 2.
Distribution of patients by INSS stage 1 through 3 and IDRF status into INRGSS L1 and L2 (n = 2,192 patients with INRGSS L1 or L2 tumors). IDRF, image-defined risk factor; INRGSS, International Neuroblastoma Risk Group Staging System; INSS, International Neuroblastoma Staging System.
Fig 3.
EFS survival-tree regression of 4,569 patients enrolled on the Children’s Oncology Group NB biology and banking study ANBL00B1 between August 18, 2006, and June 30, 2016. Quoted values are 3-year EFS and OS rates. Diff, differentiated; EFS, event-free survival; GNB, ganglioneuroblastoma; GNBI, ganglioneuroblastoma, intermixed; Ind, indeterminate; INRG, International Neuroblastoma Risk Group; MKI, mitosis-karyorrhexis index; NB, neuroblastoma; OS, overall survival; Undiff, undifferentiated.
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