Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

Greenberger, Benjamin A.; Pulsifer, Margaret B.; Ebb, David H.; MacDonald, Shannon M.; Jones, Robin M.; Butler, William E.; Huang, Mary; Marcus, Karen J.; Oberg, Jennifer A.; Tarbell, Nancy J.; Yock, Torunn I.

doi:10.1016/j.ijrobp.2014.04.053

Cited by 176 publications

(136 citation statements)

References 34 publications

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“…These results follow recent reports of cognitive outcome in much smaller samples following PRT for ependymoma (FSIQ, N = 14) 18 and low-grade glioma (FSIQ, N=12) 19 that found generally preserved functioning, but with some indications of decline for children age <7 years.…”

Section: Discussionsupporting

confidence: 90%

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

Pulsifer

Sethi

Kuhlthau

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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106

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Purpose Proton radiation therapy (PRT) offers the potential of effective treatment with minimal irradiation to normal tissue, mitigating late effects in children requiring radiotherapy for brain tumors. This longitudinal study reports cognitive outcome in pediatric patients treated with PRT for central nervous system (CNS) tumors. Methods and Materials Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterwards (follow-up). Patients were ≥ 6 years at baseline to ensure consistency in neurocognitive measures. Results Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). PRT included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ (FSIQ) was 104.6; means of all four Index scores were also in the average range. At follow-up, no significant change was observed in mean FSIQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects < 12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, SES, chemotherapy or history of surgical resection. Conclusions Early cognitive outcomes following PRT for pediatric CNS tumors are encouraging, compared to published outcomes from photon RT.

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Section: Discussionsupporting

confidence: 90%

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

Pulsifer

Sethi

Kuhlthau

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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106

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“…The clinical benefit of PRT, however, is less clear. Reports on PRT for pediatric ependymomas [16], medullablastomas [23], and gliomas [10] show encouraging rates of acute toxicity. But as a newly emerging technique, data on long-term toxicity in the pediatric population is sparse.…”

Section: Discussionmentioning

confidence: 99%

Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics

Grant

Grosshans

Bilton

et al. 2015

Radiotherapy and Oncology

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Purpose We evaluated acute toxicity profiles and dosimetric data for children with salivary gland tumors treated with adjuvant photon/electron-based radiation therapy (X/E RT) or proton therapy (PRT). Methods and Materials We identified 24 patients who had received adjuvant radiotherapy for salivary gland tumors. Data was extracted from the medical records and the treatment planning systems. Toxicity was scored according to the Common Terminology Criteria for Adverse Effects 4.0. Results Eleven patients received X/E RT and 13 PRT, with a median prescribed dose of 60 Gy in each group. In the X/E RT group, 54% of patients developed acute grade II/III dermatitis, 27% grade II/III dysphagia, and 91% grade II/III mucositis, and the median weight loss was 5.3% with one patient requiring feeding tube placement. In the PRT group, 53% had acute grade II/III dermatitis, 0% grade II/III dysphagia, and 46% grade II/III mucositis, with a median weight gain of 1.2%. Additionally, PRT was associated with lower mean doses to several normal surrounding midline and contralateral structures. Conclusion In this retrospective study of pediatric salivary tumors, PRT was associated with a favorable acute toxicity and dosimetric profile. Continued follow-up is needed to identify long-term toxicity and survival data.

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“…14 Finally, a recent report found no difference between baseline and follow-up IQ scores (1 to 8 years after PBRT) in patients with low-grade glioma (n = 12). 15 Considering the small samples and lack of comparison groups, these early reports leave much unknown regarding the neurocognitive impact of PBRT in pediatric patients with brain tumors.…”

Section: Introductionmentioning

confidence: 99%

Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors

Kahalley

Ris

Grosshans

et al. 2016

JCO

150

134

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Purpose Compared with photon radiation (XRT), proton beam radiation therapy (PBRT) reduces dose to normal tissues, which may lead to better neurocognitive outcomes. We compared change in intelligence quotient (IQ) over time in pediatric patients with brain tumors treated with PBRT versus XRT. Patients and Methods IQ scores were available for 150 patients (60 had received XRT, 90 had received PBRT). Linear mixed models examined change in IQ over time since radiation therapy (RT) by RT group, controlling for demographic/clinical characteristics. Craniospinal and focal RT subgroups were also examined. Results In the PBRT group, no change in IQ over time was identified (P = .130), whereas in the XRT group, IQ declined by 1.1 points per year (P = .004). IQ slopes did not differ between groups (P = .509). IQ was lower in the XRT group (by 8.7 points) versus the PBRT group (P = .011). In the craniospinal subgroup, IQ remained stable in both the PBRT (P = .203) and XRT groups (P = .060), and IQ slopes did not differ (P = .890). IQ was lower in the XRT group (by 12.5 points) versus the PBRT group (P = .004). In the focal subgroup, IQ scores remained stable in the PBRT group (P = .401) but declined significantly in the XRT group by 1.57 points per year (P = .026). IQ slopes did not differ between groups (P = .342). Conclusion PBRT was not associated with IQ decline or impairment, yet IQ slopes did not differ between the PBRT and XRT groups. It remains unclear if PBRT results in clinically meaningful cognitive sparing that significantly exceeds that of modern XRT protocols. Additional long-term data are needed to fully understand the neurocognitive impact of PBRT in survivors of pediatric brain tumors.

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Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

Cited by 176 publications

References 34 publications

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics

Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors

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