Abstract
Simple SummarySince inception, radiation therapy in pediatric brain tumor patients has been associated with neurocognitive decline and persistent impairment. Recently published studies suggest improved cognitive outcomes with advanced radiation techniques due to increased conformality. Our study compares different treatment modalities through longitudinal assessment of seven neurocognitive domains as well as examining the overall effect on scholastic performance in long-term follow-up more than four years after treatment. Comprehensive data were available due to interdisciplinary cooperation of pediatric neuro-oncologists, radiation oncologists, neurosurgeons, and clinical psychologists. To our knowledge, only a few such detailed testing results have been published, allowing a more granular examination of neurocognitive outcomes rather than basic IQ testing. Our study was able to show no differences in performance after adding modern conformal proton or photon radiation therapy to surgery compared to surgery alone. We could rule out radiation therapy as severe confounding factor in neurocognitive decline after brain tumor treatment in our study.Advanced radiation techniques can reduce the severity of neurocognitive sequelae in young brain tumor patients. In the present analysis, we sought to compare neurocognitive outcomes after proton irradiation with patients who underwent photon radiotherapy (RT) and surgery. Neurocognitive outcomes were evaluated in 103 pediatric brain tumor patients (proton RT n = 26, photon RT n = 30, surgery n = 47) before and after treatment. Comparison of neurocognitive outcomes following different treatment modalities were analyzed over four years after treatment completion. Longitudinal analyses included 42 months of follow-up after proton RT and 55 months after photon RT and surgery. Neurocognitive assessment included standardized tests examining seven domains. A comparison of neurocognitive outcomes after RT (proton and photon with >90% additional surgery) and surgery showed no significant differences in any neurocognitive domain. Neurocognitive functioning tests after proton RT failed to identify alterations compared to baseline testing. Long-term follow up over four years after photon RT showed a decrease in non-verbal intelligence (−9.6%; p = 0.01) and visuospatial construction (−14.9%; p = 0.02). After surgery, there was a decline in non-verbal intelligence (−10.7%; p = 0.01) and processing speed (14.9%; p = 0.002). Differences in neurocognitive outcomes between RT and surgical cohorts in direct intermodal comparison at long-term follow-up were not identified in our study, suggesting that modern radiation therapy does not affect cognition as much as in the past. There were no alterations in long-term neurocognitive abilities after proton RT, whereas decline of processing speed, non-verbal intelligence, and visuospatial abilities were observed after both photon RT and surgery. Domains dependent on intact white matter structures appear particularly vulnerable to brain tumor treatment irrespective of treatment approach.
Highlights
Tumors of the central nervous system are frequently encountered in pediatric oncology, accounting for approximately 20% of all childhood malignancies [1,2]
Examining the longitudinal development of neurocognitive domains after treatment, we found no decline after proton RT, but the domains of processing speed and visuospatial construction were compromised after photon RT, whereas processing speed and nonverbal intelligence declined following surgical intervention
In our retrospectively assessed data with small patient cohorts we found worse neurocognitive outcomes in the domains of processing speed, working memory, visuospatial construction, and verbal memory in patients with infratentorial tumor sites compared to supratentorial tumor localization, especially in the radiation therapy groups
Summary
Tumors of the central nervous system are frequently encountered in pediatric oncology, accounting for approximately 20% of all childhood malignancies [1,2]. Thanks to improved multimodality therapy, survival rates have increased over the last several decades. Trials utilizing less conformal radiation (RT) techniques [3,4,5,6,7,8] show a neurocognitive decline after treatment. Suggest that increased RT conformality, achieved via IMRT Modulated Radiation Therapy) or proton RT [9,10] lead to fewer long-term deficits in neurocognitive function [7,11,12,13,14]. The primary aim of the present study is to compare the neurocognitive outcome of pediatric brain tumor patients after multimodal brain tumor therapy, especially comparing the main risk factors for neurocognitive decline: proton RT, photon RT, or surgery alone. We investigated differences in the longitudinal development of numerous neurocognitive domains after treatment and sought to elucidate the vulnerability of specific domains by neuroanatomic deficits
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