Show simple item record

dc.contributor.authorApplebaum, MA
dc.contributor.authorVaksman, Z
dc.contributor.authorLee, SM
dc.contributor.authorHungate, EA
dc.contributor.authorHenderson, TO
dc.contributor.authorLondon, WB
dc.contributor.authorPinto, N
dc.contributor.authorVolchenboum, SL
dc.contributor.authorPark, JR
dc.contributor.authorNaranjo, A
dc.contributor.authorHero, B
dc.contributor.authorPearson, AD
dc.contributor.authorStranger, BE
dc.contributor.authorCohn, SL
dc.contributor.authorDiskin, SJ
dc.date.accessioned2018-02-20T11:58:48Z
dc.date.issued2017-02
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2017, 72 pp. 177 - 185
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1397
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2016.11.022
dc.description.abstractBackground The incidence of second malignant neoplasm (SMN) within the first ten years of diagnosis in high-risk neuroblastoma patients treated with modern, intensive therapy is unknown. Further, the underlying germline genetics that contribute to SMN in these survivors are not known.Methods The International Neuroblastoma Risk Group (INRG) database of patients diagnosed from 1990 to 2010 was analysed. SMN risk was accessed by cumulative incidence, standardised incidence ratios (SIRs) and absolute excess risk. A candidate gene-based association study evaluated genetic susceptibility to SMN in neuroblastoma survivors.Results Of the 5987 patients in the INRG database with SMN data enrolled in a clinical trial, 43 (0.72%) developed a SMN. The 10-year cumulative incidence of SMN for high-risk patients was 1.8% (95% confidence interval [CI] 1.0-2.6%) compared with 0.38% (95% CI: 0.22-0.94%) for low-risk patients (P = 0.01). High-risk patients had an almost 18-fold higher incidence of SMN compared to age- and sex-matched controls (SIR = 17.5 (95% CI: 11.4-25.3), absolute excess risk = 27.6). For patients treated on high- and intermediate-risk clinical trials, the SIR of acute myelogenous leukaemia was 106.8 (95% CI: 28.7-273.4) and 127.7 (95%CI: 25.7-373.3), respectively. Variants implicating DNA repair genes XRCC3 (rs861539: P = 0.006; odds ratio: 2.04, 95%CI: 1.19-3.46) and MSH2 (rs17036651: P = 0.009; odds ratio: 0.26, 95% CI: 0.08-0.81) were associated with SMN.Conclusion The intensive multi-modality treatment strategy currently used to treat high-risk neuroblastoma is associated with a significantly increased risk of secondary acute myelogenous leukaemia. Defining the interactions of treatment exposures and genetic factors that promote the development of SMN is critical for optimising survivorship care.
dc.formatPrint-Electronic
dc.format.extent177 - 185
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectNeuroblastoma
dc.subjectNeoplasms, Second Primary
dc.subjectGenetic Predisposition to Disease
dc.subjectCombined Modality Therapy
dc.subjectIncidence
dc.subjectRisk Assessment
dc.subjectRisk Factors
dc.subjectDNA Repair
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectSurvivors
dc.subjectFemale
dc.subjectMale
dc.subjectLeukemia, Myeloid, Acute
dc.subjectYoung Adult
dc.subjectGenetic Association Studies
dc.titleNeuroblastoma survivors are at increased risk for second malignancies: A report from the International Neuroblastoma Risk Group Project.
dc.typeJournal Article
dcterms.dateAccepted2016-11-15
rioxxterms.versionofrecord10.1016/j.ejca.2016.11.022
rioxxterms.licenseref.startdate2017-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume72
pubs.embargo.termsNot known
dc.contributor.icrauthorMarsden,en


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record