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. 2025 May 30;15:1554765. doi: 10.3389/fonc.2025.1554765

Table 2.

The potential non-cancer effects of proton therapy, such as neurocognitive function, growth and development, and quality of life in pediatric patients.

Author Patients PRT initiation age [yrs] Cancer type Type of PBT Medium dose [Gy] CRT Post-PRT observation time [yrs] Incidence of neurocognitive impairment
Mash et al. (2023)
(27)
12 4.6 Low-Grade Glioma
Embryonal tumor
Ependymoma
53.55 ± 8.9 No incidence
of neurocognitive impairment:
No changes in white matter integrity.
Ali
et al. (2021)
(28)
41 2.0 Glioma-42.3%
Medulloblastoma/
PNET-7.7%
Ependymoma-19.2%
Atypical teratoid rhabdoid tumor
Primitive neuroectodermal tumor
Germinoma – 11.52%
Other-15.4%
nd + 2.3 No incidence
of neurocognitive impairment
Child
et al.
(2021)
(29)
58 7.7 Glioma-25.9%
Medulloblastoma/
PNET-32.7%
Ependymoma-13.9%
Germ Cell Tumor-17.2%
Other-10.3%
PS F: 50.4
CSI: 54.0
nd 6.1 Variable - F vs CSI:
FSIQ - 13.3% vs 28.6%)
VCI - 3.3% vs 28.6%
PRI – 10% vs 17.9%),
WMI - 10% (F), 17.9%
PSI – 30% vs 46.4%
Fine Motor – 26.7% vs 60.7
Switching (Verbal) - 26.7% vs 17.9%
Switching (Graphomotor) – 30% vs 46.4%
Inhibition/Switching – 23.3% vs 32.1%
Verbal Learning – 20% vs 32.1%
Verbal Memory vs16.7% vs 21.4%
Visual Learning 10% vs 25%
Visual Memory 13.3% vs 14.3%
Attention 13.3% vs 17.9%
Omissions 3.3% vs 10.7%
Reading fluency 23.3% vs 42.9%
Writing fluency 26.7% vs 53.6%
Math Fluency 33.3% vs 42.9%
Weusthof et al. (2021)
(30)
26 9.4 Glioma-42.3%
Medulloblastoma/
PNET-7.7%
Ependymoma-19.2%
Craniopharyngioma – 3.8*
Germinoma – 11.52%
Other-15.4%
51.3 ± 3.5 No incidence
of neurocognitive impairment
Yip et al. (2020)
(31)
14 Medulloblastoma – 36.0% nd nd 4.3 No incidence
of neurocognitive impairment
Kahalley et al.
(2020)
(32)
37 8.6 Medulloblastoma PBS 54.0 10 No incidence
of neurocognitive impairment
Gross
et al. (2019)
(33)
58 7.4 Craniopharyngioma - 8.6%
Medulloblastoma/PNET - 44.8%
Ependymoma –8.6%
Germinoma -15.5%
Glioma -15.5%
Other - 6.9%
nd ± 2.6 No incidence
of neurocognitive impairment
Peterson et al. (2019)
(34)
22 10.0 nd nd nd nd No incidence
of neurocognitive impairment
Yang et al. (2018)
(35)
4 5.9 Atypical meningioma Retinoblastoma
Ependymoma
PBS nd + nd No incidence
of neurocognitive impairment
Pulsifer
et al. (2018)
(36)
60 12.3 Medulloblastoma – 38.3%
Gliomas – 18.3%
Craniopharyngioma – 15.0%
Ependymoma – 11.7%
Other – 16.7%
PBS 52.2 ± 3.6 FSIQ – 40%
Processing Speed – 35%
Kahalley et al. (2016)
(37)
90 9.2 Glioma – 22.2%
Medulloblastoma/PNET – 37.8%
Ependymoma – 4.4%
Germ cell tumor – 18.9%
Other – 16.7%
90% PS
10% PBS
54 5 No incidence
of neurocognitive impairment

CRT, conformal radiotherapy; CSI, craniospinal irradiation; F, focal; FSIQ, Full Scale Intelligence Quotient; nd, no data; PRI, Perceptual Reasoning Index; PSI, Processing Speed Index; VCI, Verbal Comprehension Index; WMI, Working Memory Index.; PBS, PS.