Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

Gupta, Tejpal; Jalali, Rakesh; Goswami, Sumanta; Nair, Vimoj; Moiyadi, Aliasgar; Epari, Sridhar; Sarin, Rajiv

doi:10.1016/j.ijrobp.2011.10.037

Cited by 30 publications

(23 citation statements)

References 21 publications

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“…These results also parallel those reported by Carrie et al 22 and Gupta et al 23 that children treated with HFRT displayed more preserved cognitive functions when compared with historical controls. IQ deficits in MB survivors are probably due to a diminished ability to acquire new information, rather than the loss of previously acquired knowledge 15 .…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 90%

“…On one hand, these results follow the findings of Gupta et al 23 who indicated the absence of any decreasing trend on measures of FSIQ, VIQ and PIQ for patients allocated to HFRT, when compared with historical controls. On the other hand, the results of the analyses performed with the full sample contrasts with an established body of literature documenting an IQ decline in MB survivors 22,37 , suggesting a possible overall improvement of MB treatments, regardless of radiotherapy fractionation, as suggested earlier regarding the protection of the temporal and occipital lobes.…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 89%

“…Compared with standard fractionated treatment (STRT), HFRT can be utilised either to maintain a given anti-tumour effect while decreasing unwanted effects on the CNS, or to increase the anti-tumour effect without increasing unwanted effects on the CNS. Previous uncontrolled studies of Carrie et al 22 and Gupta et al 23 reported higher post-treatment full-scale IQ in patients receiving twice-daily HFRT, compared to historical controls receiving once-daily STRT. However, using historical controls instead of a controlled experimental randomized design, limits the interpretation of these data.…”

Section: Introductionmentioning

confidence: 90%

“…This study 25 indicated significantly better executive functioning for children and young adults treated with HFRT compared with STRT, in accordance with Carrie et al 22 and Gupta el al. 23 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

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Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

Câmara-Costa

Resch

Kieffer

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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AcknowledgmentsThe authors wish to thank the participant families and the PNET4 committee and all the PNET 4 investigators. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT SummaryCognitive performance (Intelligence Quotient) in children and young adults with standard risk medulloblastoma in the XXXXX 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. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTCognitive performance in the XXXXX study 1 Abstract Purpose/Objective(s): In the XXX-XXXX XXXXX European 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 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.

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Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 90%

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 90%

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

See 2 more Smart Citations

Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

Câmara-Costa

Resch

Kieffer

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…New information about the biology of MB may identify selected patients for CSI dose reductions or elimination. This information is currently being used to select favorable risk patients for CSI doses as low as 15Gy [25]. As proton therapy promises to further reduce the dose to normal tissue associated with the boost phase of treatment, it is conceivable that with more advanced forms of proton therapy, including intensity-modulated proton therapy [26], selectively reducing dose to critical volumes of the brain during CSI, especially those associated with neurogenesis, might be feasible and safe.…”

Section: Discussionmentioning

confidence: 99%

Critical Combinations of Radiation Dose and Volume Predict Intelligence Quotient and Academic Achievement Scores After Craniospinal Irradiation in Children With Medulloblastoma

Merchant

Schreiber

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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Purpose To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. Methods and Materials Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99–20.11 years) with medulloblastoma received risk-adapted CSI followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years post-treatment) that included IQ (estimated-EIQ, full-scale, verbal and performance) and academic achievement (math, reading, spelling) tests. CSI consisted of 23.4Gy for average-risk patients (non-metastatic) and 36–39.6Gy for high-risk patients (metastatic or residual disease > 1.5cm2). The primary site was treated using conformal or intensity-modulated radiation therapy using a 2cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. Results A decline with time for all test scores was observed for the entire cohort. Sex, race and CSF shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25Gy, 35Gy, 45Gy and 55Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25Gy and 55Gy at 10Gy increments according to brain volume and age. Conclusions The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain sub-volumes will improve treatment planning, guide intervention, and help estimate the value of newer methods of irradiation.

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Long-Term Social Outcomes of Hyperfractionated Radiation on Childhood ALL Survivors

Tang

Alyman

Anderson

et al. 2016

Pediatr Blood Cancer

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Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

Cited by 30 publications

References 21 publications

Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

Critical Combinations of Radiation Dose and Volume Predict Intelligence Quotient and Academic Achievement Scores After Craniospinal Irradiation in Children With Medulloblastoma

Long-Term Social Outcomes of Hyperfractionated Radiation on Childhood ALL Survivors

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