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  • Purpose To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. Methods RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. Results High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log(10)TH > 0.8) or high PHOX2B (log(10)PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. Conclusion High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.
  • Purpose To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. Methods RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. Results High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log(10)TH > 0.8) or high PHOX2B (log(10)PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. Conclusion High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment. (en)
Title
  • Neuroblastoma mRNAs Predict Outcome in Children With Stage 4 Neuroblastoma: AEuropean HR-NBL1/SIOPEN Study
  • Neuroblastoma mRNAs Predict Outcome in Children With Stage 4 Neuroblastoma: AEuropean HR-NBL1/SIOPEN Study (en)
skos:prefLabel
  • Neuroblastoma mRNAs Predict Outcome in Children With Stage 4 Neuroblastoma: AEuropean HR-NBL1/SIOPEN Study
  • Neuroblastoma mRNAs Predict Outcome in Children With Stage 4 Neuroblastoma: AEuropean HR-NBL1/SIOPEN Study (en)
skos:notation
  • RIV/00216208:11130/14:10292992!RIV15-MSM-11130___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
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http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 32244
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11130/14:10292992
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • oncology group; randomized-trial; molecular-detection; prognostic indicator; qrt-pcr; tyrosine-hydroxylase; bone-marrow; time rt-pcr; high-risk neuroblastoma; minimal residual disease (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [2F482D8B483A]
http://linked.open...i/riv/nazevZdroje
  • Journal of Clinical Oncology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 32
http://linked.open...iv/tvurceVysledku
  • Vícha, Aleš
  • Brock, Penelope
  • Burchill, Susan A.
  • Corrias, Maria V.
  • Dallorso, Sandro
  • Gregory, Walter M.
  • Ladenstein, Ruth
  • Laureys, Genevieve
  • Luksch, Roberto
  • Papadakis, Vassilios
  • Pearson, Andrew D.
  • Swerts, Katrien
  • Tchirkov, Andrei
  • Valteau-Couanet, Dominique
  • Viprey, Virginie F.
http://linked.open...ain/vavai/riv/wos
  • 000335138400017
issn
  • 0732-183X
number of pages
http://bibframe.org/vocab/doi
  • 10.1200/JCO.2013.53.3604
http://localhost/t...ganizacniJednotka
  • 11130
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