Cargando…
QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS
Relationships between biological factors (genetic, tumour molecular subgroup) and neurocognitive/Quality of Survival (QoS) outcomes in medulloblastoma survivors are emerging, based on studies of limited retrospective cohorts. Integrated investigations of the medulloblastoma late-effects pathway (con...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715342/ http://dx.doi.org/10.1093/neuonc/noaa222.679 |
_version_ | 1783618933362786304 |
---|---|
author | Chevignard, Mathilde Bull, Kim Holt, James Heng, Marie-Amelie Kennedy, Colin Doz, Francois Lannering, Birgitta Rutkowski, Stefan Massimino, Maura Clifford, Steven Hicks, Debbie |
author_facet | Chevignard, Mathilde Bull, Kim Holt, James Heng, Marie-Amelie Kennedy, Colin Doz, Francois Lannering, Birgitta Rutkowski, Stefan Massimino, Maura Clifford, Steven Hicks, Debbie |
author_sort | Chevignard, Mathilde |
collection | PubMed |
description | Relationships between biological factors (genetic, tumour molecular subgroup) and neurocognitive/Quality of Survival (QoS) outcomes in medulloblastoma survivors are emerging, based on studies of limited retrospective cohorts. Integrated investigations of the medulloblastoma late-effects pathway (considering biological, clinical and treatment factors), using larger clinically-controlled cohorts, are now essential to determine their independent significance and potential for clinical application. In a combined cohort of SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 patients (n=150), molecular subgroup (MB(WNT), MB(SHH), MB(Grp3), MB(Grp4)) was assessed against QoS measures [health status: HUI3; emotional and behavioural difficulties: SDQ; Health-related Quality of Life (HrQoL): PedsQL]. Additionally, in DNA remaining from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs (involved in metabolism, DNA maintenance/repair, neural growth/repair and oxidative stress/inflammation) were genotyped by multiplexed MALDI-TOF MassArray and assessed against Wechsler Intelligence Scale (WISC) scores. Molecular subgroup was significantly associated with HrQoL and health status in univariate analyses; MB(Grp4) predicted significantly worse outcomes than MB(SHH) and MB(Grp3) (p<0.05), but not in multivariate analyses taking into consideration other significant and reported QoS predictors (e.g. treatment, gender, age). In contrast, 6 SNPs were significantly associated with ≥1 WISC domain; 4/6 showed associations across domains. 3 SNPs were independently prognostic in multivariate analyses, and further significant associations were apparent at the gene (BDNF, APOE) and pathway (folate) level. This cross-discipline, international study encompassing two medulloblastoma trials has identified relationships between molecular subgroup, genotype and survivorship outcomes. These findings now require assessment in larger series, to inform our understanding of medulloblastoma survivorship outcomes and impact future disease management strategies. |
format | Online Article Text |
id | pubmed-7715342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77153422020-12-09 QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS Chevignard, Mathilde Bull, Kim Holt, James Heng, Marie-Amelie Kennedy, Colin Doz, Francois Lannering, Birgitta Rutkowski, Stefan Massimino, Maura Clifford, Steven Hicks, Debbie Neuro Oncol Neuropsychology/Quality of Life Relationships between biological factors (genetic, tumour molecular subgroup) and neurocognitive/Quality of Survival (QoS) outcomes in medulloblastoma survivors are emerging, based on studies of limited retrospective cohorts. Integrated investigations of the medulloblastoma late-effects pathway (considering biological, clinical and treatment factors), using larger clinically-controlled cohorts, are now essential to determine their independent significance and potential for clinical application. In a combined cohort of SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 patients (n=150), molecular subgroup (MB(WNT), MB(SHH), MB(Grp3), MB(Grp4)) was assessed against QoS measures [health status: HUI3; emotional and behavioural difficulties: SDQ; Health-related Quality of Life (HrQoL): PedsQL]. Additionally, in DNA remaining from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs (involved in metabolism, DNA maintenance/repair, neural growth/repair and oxidative stress/inflammation) were genotyped by multiplexed MALDI-TOF MassArray and assessed against Wechsler Intelligence Scale (WISC) scores. Molecular subgroup was significantly associated with HrQoL and health status in univariate analyses; MB(Grp4) predicted significantly worse outcomes than MB(SHH) and MB(Grp3) (p<0.05), but not in multivariate analyses taking into consideration other significant and reported QoS predictors (e.g. treatment, gender, age). In contrast, 6 SNPs were significantly associated with ≥1 WISC domain; 4/6 showed associations across domains. 3 SNPs were independently prognostic in multivariate analyses, and further significant associations were apparent at the gene (BDNF, APOE) and pathway (folate) level. This cross-discipline, international study encompassing two medulloblastoma trials has identified relationships between molecular subgroup, genotype and survivorship outcomes. These findings now require assessment in larger series, to inform our understanding of medulloblastoma survivorship outcomes and impact future disease management strategies. Oxford University Press 2020-12-04 /pmc/articles/PMC7715342/ http://dx.doi.org/10.1093/neuonc/noaa222.679 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Neuropsychology/Quality of Life Chevignard, Mathilde Bull, Kim Holt, James Heng, Marie-Amelie Kennedy, Colin Doz, Francois Lannering, Birgitta Rutkowski, Stefan Massimino, Maura Clifford, Steven Hicks, Debbie QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS |
title | QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS |
title_full | QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS |
title_fullStr | QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS |
title_full_unstemmed | QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS |
title_short | QOL-17. BIOLOGICAL CORRELATES OF QUALITY OF SURVIVAL AND NEUROCOGNITIVE OUTCOMES IN MEDULLOBLASTOMA; A META-ANALYSIS OF THE SIOP-UKCCSG-PNET3 AND HIT-SIOP-PNET4 TRIALS |
title_sort | qol-17. biological correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the siop-ukccsg-pnet3 and hit-siop-pnet4 trials |
topic | Neuropsychology/Quality of Life |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715342/ http://dx.doi.org/10.1093/neuonc/noaa222.679 |
work_keys_str_mv | AT chevignardmathilde qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT bullkim qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT holtjames qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT hengmarieamelie qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT kennedycolin qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT dozfrancois qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT lanneringbirgitta qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT rutkowskistefan qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT massiminomaura qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT cliffordsteven qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials AT hicksdebbie qol17biologicalcorrelatesofqualityofsurvivalandneurocognitiveoutcomesinmedulloblastomaametaanalysisofthesiopukccsgpnet3andhitsioppnet4trials |