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Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics.

ABSTRACT: Embryonal tumors (ET) of the central nervous system (CNS) in children encompass a wide clinical spectrum of aggressive malignancies. Until recently, the overlapping morphological features of these lesions posed a diagnostic challenge and undermined discovery of optimal treatment strategies. However, with the advances in genomic technology and the outpouring of biological data over the last decade, clear insights into the molecular heterogeneity of these tumors are now well delineated. The major subtypes of ETs of the CNS in children include medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and embryonal tumors with multilayered rosettes (ETMR), which are now biologically and clinically characterized as different entities. These important developments have paved the way for treatments guided by risk stratification as well as novel targeted therapies in efforts to improve survival and reduce treatment burden.

SUBMITTER: Kram DE

PROVIDER: S-EPMC6315657 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics.

Kram David E DE Henderson Jacob J JJ Baig Muhammad M Chakraborty Diya D Gardner Morgan A MA Biswas Subhasree S Khatua Soumen S

Bioengineering (Basel, Switzerland) 20180923 4

Embryonal tumors (ET) of the central nervous system (CNS) in children encompass a wide clinical spectrum of aggressive malignancies. Until recently, the overlapping morphological features of these lesions posed a diagnostic challenge and undermined discovery of optimal treatment strategies. However, with the advances in genomic technology and the outpouring of biological data over the last decade, clear insights into the molecular heterogeneity of these tumors are now well delineated. The major ...[more]

PMID: 30249036

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Project description:ImportanceThe incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk.ObjectiveTo examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years).Design, setting, and participantsIn this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018).ExposuresMaternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (≤3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered.Main outcomes and measuresHazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years.ResultsAfter 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, -0.3 [95% CI, -1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, -0.8 [95% CI, -1.7 to 0.0]) for previous use, compared with no use. No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception.Conclusions and relevanceAmong Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk.

Dataset Information

Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics.

Publications

Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics.

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