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Neuropsychological outcome of children treated for standard risk medulloblastoma in the PNET4 European randomised controlled trial of hyperfractionated (HFRT) versus standard radiotherapy (STRT) and maintenance chemotherapy

Neuropsychological outcome of children treated for standard risk medulloblastoma in the PNET4 European randomised controlled trial of hyperfractionated (HFRT) versus standard radiotherapy (STRT) and maintenance chemotherapy
Neuropsychological outcome of children treated for standard risk medulloblastoma in the PNET4 European randomised controlled trial of hyperfractionated (HFRT) versus standard radiotherapy (STRT) and maintenance chemotherapy
Purpose/Objective(s)

In the European HIT-SIOP PNET4 randomised controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated (HFRT arm, including a partially focussed boost) or standard radiation therapy (STRT arm) followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children aged <8 years at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms.

Methods and Materials

Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven’s Progressive Matrices, we estimated: Full scale Intelligence Quotient (IQ) and, when available, Verbal IQ, Performance IQ, Working Memory Index (WMI), and Processing Speed Index (PSI).

Results

Among the 137 participants [HFRT arm n=71, STRT arm n=66, 63.5% males], mean (SD) age at diagnosis and assessment respectively was 9.3 years (3.2) (40.8% aged <8 years at diagnosis), and 14.6 years (4.3). Mean (SD) FSIQ was 88 (19) and mean intergroup difference was [95% CIs] 3.88 [-2.66 to 10.42, p=.24]. No significant difference was found in children aged >8 years at diagnosis. In children aged <8 at diagnosis, a marginally significant trend towards higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI or FSIQ (mean inter-group differences [95% CIs]): VIQ (12.02 [2.37 to 21.67]) p=0.02; PIQ (3.77 [-5.19 to 12.74]) p>.10; WMI (5.20 [-2.07 to 12.47]) p>.10; PSI (10.90 [-1.54 to 23.36]) p=.08; FSIQ (5.28 [-4.23 to 14.79]) p>.10.

Conclusions

HFRT arm was associated with marginally higher VIQ in children aged <8 years at diagnosis, consistent with the previous report using questionnaire-based data. However, overall cognitive ability was not significantly different.
child, medulloblastoma, xxxx, chemotherapy, radiotherapy, outcome, cognitive function, intellectual ability, verbal ability, perceptive reasoning, processing speed, working memory, quality of survival
0360-3016
1-18
Câmara-Costa, Hugo
65b5e0c2-f6bb-4bb5-aed2-aad428619544
Resch, Anika
2072eba5-f70c-488a-9a8d-94ab55ec422a
Kieffer, Virginie
040f3c1b-ab18-49bd-b25d-134c2bf55cf8
Lalande, Clémence
10392d88-06ab-4dd0-a879-00f51a0487e7
Poggi, Geraldina
b3f8f70b-6458-4682-a874-09c811539229
Kennedy, Colin
7c3aff62-0a86-4b44-b7d7-4bc01f23ec93
Bull, Kim
751f8b25-29ba-4d4f-96e2-6c339a83a47f
Calaminus, Gabriele
5f85276d-ee2b-4336-8b0b-a94c7b69c7b2
Grill, Jacques
27893adb-54ef-4eea-98dc-d94092ff1539
Doz, François
e481a57d-379f-4fda-adae-c37581e839f7
Rutkowski, Stefan
d77a8428-40b1-468a-9cfa-c85ad1b84ee3
Massimino, Maura
4fe9b9c6-1c49-43d0-b447-4ec24488d4d4
Kortman, Rolf-Dieter
aca9e280-a1f9-4592-8a76-b7f504f2ea09
Lannering, Birgitta
c2915eb4-d616-40cb-ba22-129805101ba5
Dellatolas, Georges
b6783dfd-3f84-4cc0-8588-4e55338f48e9
Chevignard, Mathilde
4bc19521-5c91-44cd-a4ca-20197d744e7a
Câmara-Costa, Hugo
65b5e0c2-f6bb-4bb5-aed2-aad428619544
Resch, Anika
2072eba5-f70c-488a-9a8d-94ab55ec422a
Kieffer, Virginie
040f3c1b-ab18-49bd-b25d-134c2bf55cf8
Lalande, Clémence
10392d88-06ab-4dd0-a879-00f51a0487e7
Poggi, Geraldina
b3f8f70b-6458-4682-a874-09c811539229
Kennedy, Colin
7c3aff62-0a86-4b44-b7d7-4bc01f23ec93
Bull, Kim
751f8b25-29ba-4d4f-96e2-6c339a83a47f
Calaminus, Gabriele
5f85276d-ee2b-4336-8b0b-a94c7b69c7b2
Grill, Jacques
27893adb-54ef-4eea-98dc-d94092ff1539
Doz, François
e481a57d-379f-4fda-adae-c37581e839f7
Rutkowski, Stefan
d77a8428-40b1-468a-9cfa-c85ad1b84ee3
Massimino, Maura
4fe9b9c6-1c49-43d0-b447-4ec24488d4d4
Kortman, Rolf-Dieter
aca9e280-a1f9-4592-8a76-b7f504f2ea09
Lannering, Birgitta
c2915eb4-d616-40cb-ba22-129805101ba5
Dellatolas, Georges
b6783dfd-3f84-4cc0-8588-4e55338f48e9
Chevignard, Mathilde
4bc19521-5c91-44cd-a4ca-20197d744e7a

Câmara-Costa, Hugo, Resch, Anika, Kieffer, Virginie, Lalande, Clémence, Poggi, Geraldina, Kennedy, Colin, Bull, Kim, Calaminus, Gabriele, Grill, Jacques, Doz, François, Rutkowski, Stefan, Massimino, Maura, Kortman, Rolf-Dieter, Lannering, Birgitta, Dellatolas, Georges and Chevignard, Mathilde (2015) Neuropsychological outcome of children treated for standard risk medulloblastoma in the PNET4 European randomised controlled trial of hyperfractionated (HFRT) versus standard radiotherapy (STRT) and maintenance chemotherapy. International Journal of Radiation: Oncology, Biology, Physics, 1-18. (doi:10.1016/j.ijrobp.2015.04.023). (PMID:26194675)

Record type: Article

Abstract

Purpose/Objective(s)

In the European HIT-SIOP PNET4 randomised controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated (HFRT arm, including a partially focussed boost) or standard radiation therapy (STRT arm) followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children aged <8 years at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms.

Methods and Materials

Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven’s Progressive Matrices, we estimated: Full scale Intelligence Quotient (IQ) and, when available, Verbal IQ, Performance IQ, Working Memory Index (WMI), and Processing Speed Index (PSI).

Results

Among the 137 participants [HFRT arm n=71, STRT arm n=66, 63.5% males], mean (SD) age at diagnosis and assessment respectively was 9.3 years (3.2) (40.8% aged <8 years at diagnosis), and 14.6 years (4.3). Mean (SD) FSIQ was 88 (19) and mean intergroup difference was [95% CIs] 3.88 [-2.66 to 10.42, p=.24]. No significant difference was found in children aged >8 years at diagnosis. In children aged <8 at diagnosis, a marginally significant trend towards higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI or FSIQ (mean inter-group differences [95% CIs]): VIQ (12.02 [2.37 to 21.67]) p=0.02; PIQ (3.77 [-5.19 to 12.74]) p>.10; WMI (5.20 [-2.07 to 12.47]) p>.10; PSI (10.90 [-1.54 to 23.36]) p=.08; FSIQ (5.28 [-4.23 to 14.79]) p>.10.

Conclusions

HFRT arm was associated with marginally higher VIQ in children aged <8 years at diagnosis, consistent with the previous report using questionnaire-based data. However, overall cognitive ability was not significantly different.

Other
1-s2.0-S036030161500423X-main.pdf__tid=4d2b25a8-ee8a-11e4-b53f-00000aacb35e&acdnat=1430324029_92b008f5b037a69fb3e8b841007e8e2e - Accepted Manuscript
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More information

Accepted/In Press date: 10 April 2015
e-pub ahead of print date: 17 April 2015
Additional Information: Cognitive performance (Intelligence Quotient) in children and young adults with standard risk medulloblastoma in the PNET4 randomised controlled treatment trial were compared between those allocated to hyperfractionated (HFRT arm) or standard radiation therapy (STRT arm), followed, in both treatment arms, by a standard chemotherapy regimen. Treatment with HFRT was associated with a trend towards better verbal outcomes in children aged less than 8 years at diagnosis, but no significant differences on the other cognitive measures.
Keywords: child, medulloblastoma, xxxx, chemotherapy, radiotherapy, outcome, cognitive function, intellectual ability, verbal ability, perceptive reasoning, processing speed, working memory, quality of survival
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 376604
URI: https://eprints.soton.ac.uk/id/eprint/376604
ISSN: 0360-3016
PURE UUID: 430221d6-6efe-4ff3-bb27-982a8fed81c3
ORCID for Kim Bull: ORCID iD orcid.org/0000-0002-5541-4556

Catalogue record

Date deposited: 29 Apr 2015 16:12
Last modified: 06 Jun 2018 12:54

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Contributors

Author: Hugo Câmara-Costa
Author: Anika Resch
Author: Virginie Kieffer
Author: Clémence Lalande
Author: Geraldina Poggi
Author: Colin Kennedy
Author: Kim Bull ORCID iD
Author: Gabriele Calaminus
Author: Jacques Grill
Author: François Doz
Author: Stefan Rutkowski
Author: Maura Massimino
Author: Rolf-Dieter Kortman
Author: Birgitta Lannering
Author: Georges Dellatolas
Author: Mathilde Chevignard

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