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QOL-28. Clinico-molecular correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 trials

QOL-28. Clinico-molecular correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 trials
QOL-28. Clinico-molecular correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 trials
Determinants of survivorship outcomes are emerging from limited studies of medulloblastoma (MB) survivors. We undertook an integrated analysis of biological (tumour group, host genetics) and clinico-demographic features in patients treated on the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials with available quality of survival (QoS) data (n=218), to determine key correlates of survivorship, and their clinical potential. Treatment/demographic factors and molecular subgroup (MBWNT, MBSHH, MBGrp3, MBGrp4) were assessed against health status, behavioural functioning, and health-related quality of life (HrQoL). In DNA from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs with known modifying effects on neurocognitive outcomes (e.g., involved in oxidative stress/inflammation) were genotyped and assessed against Wechsler Intelligence Scale (WISC) scores. As expected, MBSHH was associated with improved HrQoL, but subgroup did not associate further with QoS outcomes. SIOP-UKCCSG-PNET3 patients receiving chemotherapy before craniospinal irradiation (CSI) had significantly lower health status (p=0.021) and behavioural functioning (p<0.016) compared to patients treated with CSI alone, and those treated on both arms (maintenance chemotherapy and hyperfractionated (36Gy) or standard (23.4Gy) CSI) of HIT-SIOP-PNET4. SIOP-UKCCSG-PNET3 patients receiving CSI-only had better HrQoL scores than those who received pre-CSI chemotherapy and both HIT-SIOP-PNET4 arms (p=0.004). Females reported worse HrQoL/behavioural functioning across both trials (p<0.04). In HIT-SIOP-PNET4, longer intervals from diagnosis to CSI predicted worse HrQoL/health status (p<0.05). Neither molecular group nor clinico-demographic features tested were associated with neurocognition. In contrast, 6 SNPs significantly associated with ≥1 WISC domain; 4/6 showed multiple associations and were independently prognostic; further associations were apparent at the gene/pathway level. This large, integrated and multi-disciplinary analysis of two independent trials cohorts has revealed multiple factors predictive of medulloblastoma survivorship including treatment (chemotherapy, time to CSI), tumour (molecular group) and host genetic factors. Assessment in further prospective series are required to determine their potential as a basis for modifications to disease management.
1522-8517
i139-i140
Chevignard, Mathilde
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Bull, Kim S.
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Holt, James
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Harrington, Bertie
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Castle, Jemma
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Heng, Marie-amelie
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Kennedy, Colin
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Doz, Francois
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Lannering, Birgitta
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Rutkowski, Stefan
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Massimino, Maura
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Bailey, Simon
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Oyefiade, Adeoye
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Mabbott, Donald
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Clifford, Steven C
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Hicks, Debbie
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Chevignard, Mathilde
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Bull, Kim S.
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Holt, James
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Harrington, Bertie
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Castle, Jemma
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Heng, Marie-amelie
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Kennedy, Colin
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Doz, Francois
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Lannering, Birgitta
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Rutkowski, Stefan
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Massimino, Maura
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Bailey, Simon
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Oyefiade, Adeoye
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Mabbott, Donald
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Clifford, Steven C
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Hicks, Debbie
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Chevignard, Mathilde, Bull, Kim S., Holt, James, Harrington, Bertie, Castle, Jemma, Heng, Marie-amelie, Kennedy, Colin, Doz, Francois, Lannering, Birgitta, Rutkowski, Stefan, Massimino, Maura, Bailey, Simon, Oyefiade, Adeoye, Mabbott, Donald, Clifford, Steven C and Hicks, Debbie (2022) QOL-28. Clinico-molecular correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 trials. Neuro-Oncology, 24 (Supplement_1), i139-i140. (doi:10.1093/neuonc/noac079.511).

Record type: Meeting abstract

Abstract

Determinants of survivorship outcomes are emerging from limited studies of medulloblastoma (MB) survivors. We undertook an integrated analysis of biological (tumour group, host genetics) and clinico-demographic features in patients treated on the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials with available quality of survival (QoS) data (n=218), to determine key correlates of survivorship, and their clinical potential. Treatment/demographic factors and molecular subgroup (MBWNT, MBSHH, MBGrp3, MBGrp4) were assessed against health status, behavioural functioning, and health-related quality of life (HrQoL). In DNA from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs with known modifying effects on neurocognitive outcomes (e.g., involved in oxidative stress/inflammation) were genotyped and assessed against Wechsler Intelligence Scale (WISC) scores. As expected, MBSHH was associated with improved HrQoL, but subgroup did not associate further with QoS outcomes. SIOP-UKCCSG-PNET3 patients receiving chemotherapy before craniospinal irradiation (CSI) had significantly lower health status (p=0.021) and behavioural functioning (p<0.016) compared to patients treated with CSI alone, and those treated on both arms (maintenance chemotherapy and hyperfractionated (36Gy) or standard (23.4Gy) CSI) of HIT-SIOP-PNET4. SIOP-UKCCSG-PNET3 patients receiving CSI-only had better HrQoL scores than those who received pre-CSI chemotherapy and both HIT-SIOP-PNET4 arms (p=0.004). Females reported worse HrQoL/behavioural functioning across both trials (p<0.04). In HIT-SIOP-PNET4, longer intervals from diagnosis to CSI predicted worse HrQoL/health status (p<0.05). Neither molecular group nor clinico-demographic features tested were associated with neurocognition. In contrast, 6 SNPs significantly associated with ≥1 WISC domain; 4/6 showed multiple associations and were independently prognostic; further associations were apparent at the gene/pathway level. This large, integrated and multi-disciplinary analysis of two independent trials cohorts has revealed multiple factors predictive of medulloblastoma survivorship including treatment (chemotherapy, time to CSI), tumour (molecular group) and host genetic factors. Assessment in further prospective series are required to determine their potential as a basis for modifications to disease management.

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e-pub ahead of print date: 3 June 2022
Published date: 3 June 2022
Venue - Dates: 20th International Symposium on Pediatric Neuro-Oncology, Congress Center Hamburg, Hamburg, Germany, 2022-06-12 - 2022-06-15

Identifiers

Local EPrints ID: 467675
URI: http://eprints.soton.ac.uk/id/eprint/467675
ISSN: 1522-8517
PURE UUID: c034bf2a-04fe-4147-ae35-84bad6829bd0
ORCID for Kim S. Bull: ORCID iD orcid.org/0000-0002-5541-4556

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Date deposited: 19 Jul 2022 16:37
Last modified: 29 Jul 2022 01:37

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Contributors

Author: Mathilde Chevignard
Author: Kim S. Bull ORCID iD
Author: James Holt
Author: Bertie Harrington
Author: Jemma Castle
Author: Marie-amelie Heng
Author: Colin Kennedy
Author: Francois Doz
Author: Birgitta Lannering
Author: Stefan Rutkowski
Author: Maura Massimino
Author: Simon Bailey
Author: Adeoye Oyefiade
Author: Donald Mabbott
Author: Steven C Clifford
Author: Debbie Hicks

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