Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors

doi:10.1016/j.ijrobp.2018.05.069

International Journal of Radiation OncologyBiologyPhysics

Volume 102, Issue 2, 1 October 2018, Pages 391-398

https://doi.org/10.1016/j.ijrobp.2018.05.069 Get rights and content

Purpose

Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam radiation therapy (PRT), which enables better focusing of radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT.

Methods and Materials

A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irradiation [CSI; 39%] and focal irradiation [61%]).

Results

Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups.

Conclusions

At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type.

Introduction

Multimodality approaches that integrate surgery, chemotherapy, and radiation therapy have reduced mortality outcomes for pediatric patients with brain tumor (1). However, long-term effects of radiation therapy on cognitive and adaptive functioning are a major complication for survivors of childhood tumors 2, 3, 4, 5, 6, 7, with younger patients typically manifesting greater cognitive deficits 8, 9, 10, 11, 12. Therefore, it has been common practice to avoid use of radiation in children under the age of 3 years (11). Radiation appears to have a disproportionate effect on white matter 11, 12, 13, 14, and the rapid development of white matter in early childhood might be one reason why younger children are at greater risk for negative cognitive sequelae, including impairments of processing speed and working memory 12, 15, 16. Such impairments might lead to further difficulties later in life by preventing development of necessary skills at age-appropriate rates.

Adaptive functioning is the ability to perform tasks of daily living at an age-appropriate level. It provides a practical overall indication of the level of development and need for services at all ages. Ample evidence indicates that children with brain tumors are vulnerable to declines in adaptive functioning (17), but few studies have examined if or how radiation therapy affects that risk 6, 18. Recent investigations of outcome after conformal photon radiation have found fairly stable overall adaptive functioning (19), although there is also evidence of impairments in the areas of communication and socialization 20, 21.

Proton beam radiation therapy (PRT) reduces radiation dose to normal tissues compared with photon radiation therapy and may thereby reduce long-term side effects 22, 23, 24, 25. A prior study examining the effects of PRT on cognitive functioning in patients aged 6 to 21 years found that overall IQ remained stable at about 3 years after treatment but that processing speed was negatively affected (26). The present paper follows up on those results with the addition of a younger cohort (<6 years of age) and, for some patients, later follow-up assessments. Little research has been conducted on the effects of PRT on adaptive functioning in any age group.

The aim of the current study is to examine cognitive and adaptive functioning in a large cohort of patients, aged 1 to 22 years at treatment, who received diagnosis of a brain tumor and received PRT. The findings may help inform treatment decisions for the care of pediatric patients who receive a diagnosis of brain tumor.

Section snippets

Patients and procedures

The study cohort included 155 patients treated with PRT at the Massachusetts General Hospital (MGH) Francis H. Burr Proton Center for a primary brain tumor. The patients received baseline cognitive and adaptive testing at MGH as part of their routine clinical care between 2002 and 2017. Patients were ≤22 years at baseline (defined as immediately before or during PRT), had no prior diagnosis of brain or central nervous system tumor, and had follow-up assessment through MGH at least 1 year after

Patient characteristics

Demographic and clinical characteristics are summarized in Table 1. The mean age at baseline was 8.9 years, with 36.8% of the sample in the younger group. Age at baseline was not significantly related to sex, hydrocephalus at diagnosis, treatment with CSI or focal PRT, treatment with chemotherapy, motor or sensory deficits at baseline, or socioeconomic status (SES). The mean follow-up interval for the younger CSI group was significantly longer than that for the other 3 groups (P = .03); no

Discussion

The present study investigates cognitive and adaptive outcome at an average of 3.6 years posttreatment in a large group of pediatric patients with brain tumor treated with PRT. We found a small but statistically significant decline in mean cognitive scores for the total sample, and a greater time interval between baseline and follow-up testing was associated with greater cognitive decline for the total sample. However, the overall mean FSIQ/MDI score was in the average range at both baseline

Conclusions

The present study examined cognitive and adaptive functioning in a large cohort aged 1 to 22 years and treated with PRT for primary brain tumor. Patients under 6 years of age treated with CSI exhibited a significantly greater decline in IQ than did patients treated with focal PRT and older patients. Processing speed and working memory skills were significantly lower at follow-up for patients treated with CSI, regardless of age. No significant change in adaptive functioning was found after PRT,

Acknowledgments

The authors thank the MGH Francis Burr Proton Center pediatric patients and their families for participation in this study.

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: This project was supported by Award Number P01CA021239 from the National Cancer Institute. This report does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The project also was supported by the Federal Share of program income earned by the Massachusetts General Hospital (MGH) on C06 CA059267 Proton Therapy Research and Treatment Center.

: This study is registered at ClinicalTrials.gov, number NCT01180881.

: Conflict of interest: none.

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Clinical InvestigationCognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Patients and procedures

Patient characteristics

Discussion

Conclusions

Acknowledgments

Lancet Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lancet Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiotherapy for pediatric brain tumors: When and how

Expert Rev Anticancer Ther

Neurocognitive consequences of a paediatric brain tumour and its treatment: A meta-analysis

J Dev Med Child Neurol

Impact of cranial dose, boost volume, and neurological complications on intellectual outcome in patients with medulloblastoma

J Clin Oncol

Adaptive functioning of childhood brain tumor survivors following conformal radiation therapy

J Neurooncol

Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: Prospective evaluation of cognitive, endocrine, and hearing deficits

J Clin Oncol

Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma

J Clin Oncol

Processing speed, attention, and working memory after treatment for medulloblastoma: An international, prospective, and longitudinal study

J Clin Oncol

Neuropsychological impact of treatment of brain tumors

Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss

J Clin Oncol

Atypical white matter volume development in children following craniospinal irradiation

Neuro-Oncol

Neurobehavioral effects of central nervous system prophylactic treatment of cancer in children

J Clin Exp Neuropsych

White matter integrity is associated with cognitive processing in patients treated for a posterior fossa brain tumor

Neuro-Oncol

Clinical Investigation
Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors