Universität zu Köln

Campbell, Kevin, Shyr, Derek, Bagatell, Rochelle, Fischer, Matthias, Nakagawara, Akira, Canete Nieto, Adela, Brodeur, Garrett M., Matthay, Katherine K., London, Wendy B. and DuBois, Steven G. (2019). Comprehensive evaluation of context dependence of the prognostic impact of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project. Pediatr. Blood Cancer, 66 (8). HOBOKEN: WILEY. ISSN 1545-5017

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Abstract

Background MYCN amplification (MYCN-A) is an established adverse prognostic factor in neuroblastoma. The extent to which the prognostic impact of MYCN-A depends on other factors has not been fully characterized. Patients and methods Using the International Neuroblastoma Risk Group database, we constructed Cox models of overall survival (OS) to obtain hazard ratios of the effect of MYCN-A within subgroups defined by other prognostic factors. Cox models assessed the degree to which the prognostic impact of MYCN-A was modulated by each other covariate. We used absolute hazard ratio (HR) differences to construct classification trees to identify subgroups with greatest differential prognostic effect of MYCN-A. Results In a cohort of 6223 patients with known MYCN status, the OS hazard ratio associated with MYCN-A was 6.3 (95% confidence interval 5.7-7.0, P < .001). Age at diagnosis conferred the largest HR absolute difference for MYCN-A between subgroups (HR absolute difference 16.6; HRs for MYCN-A of 19.6 for <18 months, 3.0 for >= 18 months). MYCN-A remained significantly prognostic of OS after controlling for other factors, abrogating their prognostic strength. Patients whose outcome was most impacted by MYCN status were those who were <18 months, had high mitosis karrhyohexis index (MKI) and low ferritin. Conclusion The prognostic strength of MYCN-A varies depending on which patient subgroup defined by other neuroblastoma risk factors is examined, with greatest strength in patients with otherwise favorable features. MYCN-A has little effect within some subgroups, aiding clinical decision-making if MYCN status cannot be assessed. Subgroups where MYCN-A has large effect may be prioritized for agents targeting Myc family proteins.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Campbell, Kevin UNSPECIFIED UNSPECIFIED UNSPECIFIED Shyr, Derek UNSPECIFIED UNSPECIFIED UNSPECIFIED Bagatell, Rochelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakagawara, Akira UNSPECIFIED UNSPECIFIED UNSPECIFIED Canete Nieto, Adela UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodeur, Garrett M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthay, Katherine K. UNSPECIFIED UNSPECIFIED UNSPECIFIED London, Wendy B. UNSPECIFIED UNSPECIFIED UNSPECIFIED DuBois, Steven G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-134341
DOI:	10.1002/pbc.27819
Journal or Publication Title:	Pediatr. Blood Cancer
Volume:	66
Number:	8
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1545-5017
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language N-MYC; PATHOLOGY CLASSIFICATION; ONCOGENE; SURVIVAL; INFANTS; MARKERS Multiple languages Oncology; Hematology; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13434