Irradiation-related longitudinal white matter atrophy underlies cognitive impairment in patients with nasopharyngeal carcinoma

Abstract

To longitudinally investigate alterations in cerebral white matter volume as a function of irradiation dose and time after standard radiotherapy in nasopharyngeal carcinoma patients and to determine how these alterations are related to radiotherapy-associated neurocognitive dysfunction.

A total of 120 nasopharyngeal carcinoma patients were included in the present study. Longitudinal structural magnetic resonance imaging was performed at pre-radiotherapy and 1–3, 6, and 9–12 months post-radiotherapy. Twenty healthy controls were recruited and followed up with in parallel. Structural images were processed via FreeSurfer. The Montreal Cognitive Assessment was performed to evaluate cognitive function of the participants. Linear mixed models and general linear models were used to evaluate different trajectories and the relationship between white matter volume and cognition in patients and controls within approximately 12 months of follow-up.

Selective and time-dependent white matter atrophy was observed in the right parahippocampal gyrus, right inferior temporal gyrus, right middle temporal gyrus, right fusiform gyrus, and left insular cortex in post-radiotherapy patients compared to the controls. Moreover, radiotherapy-associated white matter atrophy in the right parahippocampal gyrus exhibited a dose-dependent pattern, whereas radiotherapy-associated white matter atrophy in the right inferior temporal gyrus was correlated with progressive cognitive impairment in patients.

Taken together, our findings illustrate that white matter volume alterations can be used as a potential biomarker to detect radiotherapy-related subtle brain injury in nasopharyngeal carcinoma patients, which may help further elucidate the pathogenesis of radiation-induced cognitive decline and facilitate studies on cognition-sparing radiotherapy.

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Abbreviations

RT:

radiotherapy

NPC:

nasopharyngeal carcinoma;

MRI:

magnetic resonance imaging

WM:

white matter

MoCA:

Montreal Cognitive Assessment

PHG:

parahippocampal gyrus

ITG:

inferior temporal gyrus

MTG:

middle temporal gyrus

FUS:

fusiform

EDS:

early-delayed stage

LDS:

late-delayed stage

DTI:

diffusion tensor imaging

FA:

fractional anisotrophy

GM:

gray matter

AJCC:

American Joint Committee on Cancer

IMRT:

intensity-modulated radiation therapy

3D-BRAVO:

three-dimensional brain volume imaging

eTIV:

estimated total intracranial volume

LMM:

linear mixed model

GLM:

general linear model

1H-MRS:

1H-MR spectroscopy.

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Acknowledgments

We thank LetPub (www.LetPub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

This work was funded by grants from the Natural Science Foundation of China (grant numbers 81401399, 81560283, and 81201084) and Natural Science Foundation of Guangdong (grant numbers 2019A1515011143, 2020A1515011332).

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Authors

Contributions

XLv and YQiu proposed conceptions and designed the study. XLin conducted data collection and wrote the manuscript. LTang and MLi screened clinical data and original imaging data of the study. MWang collected dose data of the study. YQiu, XLv, and ZGuo performed data analysis and contributed to the revision of this manuscript.

Corresponding authors

Correspondence to Xiaofei Lv or Yingwei Qiu.

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This study was conducted in accordance with the recommendations of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and the Institutional Review Board of the Sun Yat-sen University Cancer Center.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare that they have no conflict of interest.

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Lin, X., Tang, L., Li, M. et al. Irradiation-related longitudinal white matter atrophy underlies cognitive impairment in patients with nasopharyngeal carcinoma. Brain Imaging and Behavior (2021). https://doi.org/10.1007/s11682-020-00441-0

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Keywords

  • Radiotherapy
  • NPC
  • MRI
  • Structural
  • Cognition