PMID- 32315273 OWN - NLM STAT- MEDLINE DCOM- 20210222 LR - 20210611 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 38 IP - 17 DP - 2020 Jun 10 TI - Age, Diagnostic Category, Tumor Grade, and Mitosis-Karyorrhexis Index Are Independently Prognostic in Neuroblastoma: An INRG Project. PG - 1906-1918 LID - 10.1200/JCO.19.03285 [doi] AB - 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. FAU - Sokol, Elizabeth AU - Sokol E AD - Department of Pediatrics and Lurie Children's Hospital, Northwestern University, Chicago, IL. FAU - Desai, Ami V AU - Desai AV AD - Department of Pediatrics and Comer Children's Hospital, University of Chicago, Chicago, IL. FAU - Applebaum, Mark A AU - Applebaum MA AD - Department of Pediatrics and Comer Children's Hospital, University of Chicago, Chicago, IL. FAU - Valteau-Couanet, Dominique AU - Valteau-Couanet D AD - Institute Gustave Roussy, Villejuif, France. FAU - Park, Julie R AU - Park JR AD - Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington. FAU - Pearson, Andrew D J AU - Pearson ADJ AD - Paediatric Drug Development, Children and Young People's Unit, Royal Marsden Hospital, London, United Kingdom. FAU - Schleiermacher, Gudrun AU - Schleiermacher G AD - Department of Pediatric, Adolescents and Young Adults Oncology and INSERM U830, Institut Curie, Paris, France. FAU - Irwin, Meredith S AU - Irwin MS AD - Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Ontario, Canada. FAU - Hogarty, Michael AU - Hogarty M AD - Department of Pediatrics, University of Pennsylvania, Philadelphia, PA. FAU - Naranjo, Arlene AU - Naranjo A AD - Department of Biostatistics, Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL. FAU - Volchenboum, Samuel AU - Volchenboum S AD - Department of Pediatrics and Comer Children's Hospital, University of Chicago, Chicago, IL. FAU - Cohn, Susan L AU - Cohn SL AD - Department of Pediatrics and Comer Children's Hospital, University of Chicago, Chicago, IL. FAU - London, Wendy B AU - London WB AD - Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA. LA - eng GR - U10 CA180886/CA/NCI NIH HHS/United States GR - U10 CA180899/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200421 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Biomarkers, Tumor) SB - IM CIN - J Clin Oncol. 2020 Nov 1;38(31):3719-3720. PMID: 32931395 CIN - J Clin Oncol. 2020 Nov 1;38(31):3720-3721. PMID: 32931402 MH - Adolescent MH - Age Factors MH - Biomarkers, Tumor MH - Child MH - Child, Preschool MH - Cohort Studies MH - Humans MH - Infant MH - Mitotic Index MH - Neoplasm Grading MH - Neuroblastoma/classification/*diagnosis/*pathology MH - Prognosis MH - Young Adult PMC - PMC7280049 EDAT- 2020/04/22 06:00 MHDA- 2021/02/23 06:00 PMCR- 2021/06/10 CRDT- 2020/04/22 06:00 PHST- 2020/04/22 06:00 [pubmed] PHST- 2021/02/23 06:00 [medline] PHST- 2020/04/22 06:00 [entrez] PHST- 2021/06/10 00:00 [pmc-release] AID - 1903285 [pii] AID - 10.1200/JCO.19.03285 [doi] PST - ppublish SO - J Clin Oncol. 2020 Jun 10;38(17):1906-1918. doi: 10.1200/JCO.19.03285. Epub 2020 Apr 21.