Long‐term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy

Child, Amanda; Warren, Emily; Grosshans, David R.; Paulino, Arnold C.; Okcu, M. Fatih; Ris, M. Douglas; Mahajan, Anita; Orobio, Jessica; Cirino, Paul T.; Minard, Charles G.; Viana, Andres G.; Bick, Johanna; Woods, Steven Paul; Chintagumpala, Murali; Kahalley, Lisa S.

doi:10.1002/pbc.29125

Cited by 26 publications

(40 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the previous literature, this study found that all areas of intellectual functioning were significantly lower in patients who received XRT compared to PRT, with processing speed emerging as especially vulnerable in both groups (Antonini et al, 2017; Child et al, 2021; Gross et al, 2019; Kahalley et al, 2019, 2020). Individuals receiving PRT consistently performed within typical age expectations, while the XRT group demonstrated notable deficits with respect to working memory and processing speed.…”

Section: Discussionsupporting

confidence: 91%

Superior verbal learning and memory in pediatric brain tumor survivors treated with proton versus photon radiotherapy.

Mash¹,

Kahalley²,

Okcu³

et al. 2023

Neuropsychology

Self Cite

View full text Add to dashboard Cite

Objective: Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers lower doses of radiation to healthy brain tissue. PRT has been associated with improved long-term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory. Method: Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing >1 year following radiotherapy. Performance on neuropsychological measures was compared between treatment groups using analysis of covariance. Chi-squared tests of independence were used to compare the frequency of encoding, retrieval, and intact memory profiles between treatment groups. Associations between memory performance and other neurobehavioral measures were examined using Pearson correlation. Results: Overall, patients receiving PRT demonstrated superior verbal learning and recall compared to those treated with XRT. Encoding and retrieval deficits were more common in the XRT group than the PRT group, with encoding problems being most prevalent. The PRT group was more likely to engage in semantic clustering strategies, which predicted better encoding and retrieval. Encoding ability was associated with higher intellectual and adaptive functioning, and fewer parent-reported concerns about day-to-day attention and cognitive regulation. Conclusion: Results suggest that PRT is associated with verbal memory sparing, driven by effective encoding and use of learning strategies. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline, which will better inform treatment approaches. This document is copyrighted by the American Psychological Association or one of its allied publishers.This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.Lisa E. Mash https://orcid.org/0000-0002-3425-8646 Lisa S. Kahalley received funding from Grant R01CA221197 and R01CA187202 from the Division of Cancer Prevention, National Cancer Institute. The authors have no conflict of interest to disclose.Data and analysis code for this study are available upon request. This study was not preregistered.Lisa E. Mash played lead role in conceptualization, formal analysis, methodology, software, writing of original draft and writing of review and editing. Lisa S. Kahalley played lead role in funding acquisition and equal role in conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, writing of original draft and writing of review and editing. M. Fatih Okcu played supporting role in conceptualization, data curation, investigation, methodology, project administration, resources and writing of review and editing. David R. Grosshans played supporting role in conceptualization, data curation, investigation, methodology, project administration, resources...

show abstract

Section: Discussionsupporting

confidence: 91%

Superior verbal learning and memory in pediatric brain tumor survivors treated with proton versus photon radiotherapy.

Mash¹,

Kahalley²,

Okcu³

et al. 2023

Neuropsychology

Self Cite

View full text Add to dashboard Cite

show abstract

“…No significant differences were seen for verbal reasoning and processing speed. In addition, Child et al [ 34 ] found that focal radiotherapy using protons led to favorable long-term cognitive and academic outcomes in pediatric patients. Focally irradiated children generally showed similar cognitive status to a normalized sample of children with normal development.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy with Helium Ions Has the Potential to Improve Both Endocrine and Neurocognitive Outcome in Pediatric Patients with Ependymoma

Wickert

Tessonnier

Deng

et al. 2022

Cancers

View full text Add to dashboard Cite

Ependymomas are the third most-frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Compared to photon radiation treatment, proton therapy often achieves even better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions could further reduce side effects, providing better protection of healthy tissue despite similar target coverage. In our in silico study, 15 pediatric ependymoma patients were considered. All patients underwent adjuvant radiotherapeutic treatment with active-scanned protons at Heidelberg Ion Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric advantage of ion beam therapy compared to the current state-of-the-art photon-based treatments. To estimate the potential clinical benefit of helium ions, normal tissue complication probabilities (NTCP) were calculated. Target coverage was comparable in all three modalities. As expected, the integral dose absorbed by healthy brain tissue could be significantly reduced with protons by up to −48% vs. IMRT. Even compared to actively scanned protons, relative dose reductions for critical neuronal structures of up to another −39% were achieved when using helium ions. The dose distribution of helium ions is significantly superior when compared to proton therapy and IMRT due to the improved sparing of OAR. In fact, previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose–response relationship of critical organs at risk combined with NTCP calculation, the results of our study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

show abstract

“…It is notable that survivor social outcomes did not differ based on RT modality, although significant differences in cognitive outcomes between survivors treated with XRT versus PRT extend previous studies, suggesting a potential neuroprotective benefit of PRT for cognitive skills. [24][25][26][27] Given previous associations of cognitive impairment with poor social outcomes, 12…”

Section: Discussionmentioning

confidence: 99%

Cognitive predictors of social adjustment in pediatric brain tumor survivors treated with photon versus proton radiation therapy

Warren

Raghubar

Cirino

et al. 2022

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Background Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. Procedure Survivors who underwent PRT (n = 38) or XRT (n = 20) participated in a neurocognitive evaluation >1 year post radiotherapy. Group differences in cognitive and social functioning were assessed using analysis of covariance (ANCOVA). Regression analyses examined predictors of peer relations and social skills. Results Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p > .05). XRT participants were younger at diagnosis (XRT M = 5.0 years, PRT M = 7.6 years) and further out from radiotherapy (XRT M = 8.7 years, PRT M = 4.6 years). The XRT group performed worse than the PRT group on measures of processing speed (p = .01) and verbal memory (p < .01); however, social outcomes did not differ by radiation type. The proportion of survivors with impairment in peer relations and social skills exceeded expectation; χ2(1) = 38.67, p < .001; χ2(1) = 5.63, p < .05. Household poverty predicted peer relation difficulties (t = 2.18, p < .05), and verbal memory approached significance (t = −1.99, p = .05). Tumor diameter predicted social skills (t = −2.07, p < .05). Conclusions Regardless of radiation modality, survivors are at risk for social challenges. Deficits in verbal memory may place survivors at particular risk. Results support monitoring of cognitive and social functioning throughout survivorship, as well as consideration of sociodemographic risk factors.

show abstract

Long‐term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy

Cited by 26 publications

References 35 publications

Superior verbal learning and memory in pediatric brain tumor survivors treated with proton versus photon radiotherapy.

Superior verbal learning and memory in pediatric brain tumor survivors treated with proton versus photon radiotherapy.

Radiotherapy with Helium Ions Has the Potential to Improve Both Endocrine and Neurocognitive Outcome in Pediatric Patients with Ependymoma

Cognitive predictors of social adjustment in pediatric brain tumor survivors treated with photon versus proton radiation therapy

Contact Info

Product

Resources

About