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Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group

2020-11-01Journal article Open access
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dc.contributor.authorAmbros, Inge M.
dc.contributor.authorTonini, Gian-Paolo
dc.contributor.authorPötschger, Ulrike
dc.contributor.authorGross, Nicole
dc.contributor.authorMosseri, Véronique
dc.contributor.authorBeiske, Klaus
dc.contributor.authorBerbegall, Ana P.
dc.contributor.authorBénard, Jean
dc.contributor.authorBown, Nick
dc.contributor.authorCaron, Huib
dc.contributor.authorCombaret, Valérie
dc.contributor.authorCouturier, Jerome
dc.contributor.authorDefferrari, Raffaella
dc.contributor.authorDelattre, Olivier
dc.contributor.authorJeison, Marta
dc.contributor.authorKogner, Per
dc.contributor.authorLunec, John
dc.contributor.authorMarques, Barbara
dc.contributor.authorMartinsson, Tommy
dc.contributor.authorMazzocco, Katia
dc.contributor.authorNoguera, Rosa
dc.contributor.authorSchleiermacher, Gudrun
dc.contributor.authorValent, Alexander
dc.contributor.authorVan Roy, Nadine
dc.contributor.authorVillamon, Eva
dc.contributor.authorJanousek, Dasa
dc.contributor.authorPribill, Ingrid
dc.contributor.authorGlogova, Evgenia
dc.contributor.authorAttiyeh, Edward F.
dc.contributor.authorHogarty, Michael D.
dc.contributor.authorMonclair, Tom F.
dc.contributor.authorHolmes, Keith
dc.contributor.authorValteau-Couanet, Dominique
dc.contributor.authorCastel, Victoria
dc.contributor.authorTweddle, Deborah A.
dc.contributor.authorPark, Julie R.
dc.contributor.authorCohn, Sue
dc.contributor.authorLadenstein, Ruth
dc.contributor.authorBeck-Popovic, Maja
dc.contributor.authorDe Bernardi, Bruno
dc.contributor.authorMichon, Jean
dc.contributor.authorPearson, Andrew D.J.
dc.contributor.authorAmbros, Peter F.
dc.date.accessioned2021-04-07T15:11:41Z
dc.date.available2021-04-07T15:11:41Z
dc.date.issued2020-11-01
dc.description.abstractPurpose: For localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome. Patients and methods: Diagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group. Results: Patients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] ± standard deviation [SD], 95% ± 2%; 5-year overall survival [OS], 99% ± 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS ± SD, 84% ± 3% in patients < 18 months of age and 75% ± 7% in patients ≥ 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS ± SD in < 18months and ≥ 18months, 96% ± 2% and 81% ± 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS ± SD in patients 1p loss and no 1p loss, 62% ± 13% and 87% ± 3%, respectively; P = .019) but not OS (5-year OS ± SD, 92% ± 8% and 97% ± 2%, respectively). In patients ≥ 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS ± SD, 48% ± 16% and 85% ± 7%, P = .033; 5-year OS ± SD, 46% ± 22% and 92% ± 6%, P = .038). Conclusion: Genomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.pt_PT
dc.description.sponsorshipFunded in part by Oesterreichische National Bank (Grant No. 13422), Wissenschaftsfonds FWF (Grant No. I 2799-B28), and Directorate-General V, European Commission (Grant No. SOC 98 201284 05F02), all to P.F.A.; and Instituto de Salud Carlos III (Grant No. PI17/01558) to R.N.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Clin Oncol. 2020 Nov 1;38(31):3685-3697. doi: 10.1200/JCO.18.02132. Epub 2020 Sep 9.pt_PT
dc.identifier.doi10.1200/JCO.18.02132pt_PT
dc.identifier.issn0732-183X
dc.identifier.urihttp://hdl.handle.net/10400.18/7652
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society of Clinical Oncologypt_PT
dc.relation.publisherversionhttps://ascopubs.org/doi/full/10.1200/JCO.18.02132pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAge Factorspt_PT
dc.subjectClinical Trials as Topicpt_PT
dc.subjectDiploidypt_PT
dc.subjectGene Amplificationpt_PT
dc.subjectGenomicspt_PT
dc.subjectHumanspt_PT
dc.subjectInfantpt_PT
dc.subjectN-Myc Proto-Oncogene Proteinpt_PT
dc.subjectNeoplasm Stagingpt_PT
dc.subjectNeuroblastomapt_PT
dc.subjectPrognosispt_PT
dc.subjectProgression-Free Survivalpt_PT
dc.subjectSurvival Ratept_PT
dc.subjectChromosome Aberrationspt_PT
dc.subjectChromosomes, Human, Pair 1pt_PT
dc.subjectChromosomes, Human, Pair 11pt_PT
dc.subjectPediatric Oncologypt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleAge Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Grouppt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3697pt_PT
oaire.citation.issue31pt_PT
oaire.citation.startPage3685pt_PT
oaire.citation.titleJournal of Clinical Oncologypt_PT
oaire.citation.volume38pt_PT
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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