Association of white matter hyperintensities with long-term EGFR-TKI treatment and prediction of progression risk

Hang Yang, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Rui Meng, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Junjie Jiang, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yan Luo, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiaolin Deng, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sibo Yang, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shengcai Chen, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jiehong Wu, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yan Wan, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yanan Li, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huijuan Jin, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Quanwei He, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
David Wang, Neurovascular Division, Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.Follow
Jiang Chang, Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Kunyu Yang, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yifan Zhou, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bo Hu, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Document Type

Article

Abstract

PURPOSE: The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and identify clinical risk factors associated with WMH. EXPERIMENTAL DESIGN: This multiple-center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non-small cell lung cancer (NSCLC) who received or did not receive EGFR-TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2-year follow-up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. RESULTS: Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR-TKI and 92 (32%) patients with NSCLC without EGFR-TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR-TKI treatment was independently associated with the WMH progression (EGFR-TKI: aRR 2.72, 95% confidence interval [CI] 1.46-5.06, p = .002). Interleukin (IL)-2, IL-4, and IL-10 were associated with increased WMH in the adjusted model (IL-2: aRR 1.55 [95% CI 1.06-2.25], p = .023; IL-4: aRR 1.66 [95% CI 1.13-2.43], p = .010; IL-10: aRR 1.48 [95% CI 1.06-2.06], p = .020). CONCLUSION: Patients with NSCLC who received EGFR-TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL-2, IL-4, and IL-10 may be used as potential biomarkers to monitor the risk of increased WMH burden.

Medical Subject Headings

Humans; Carcinoma, Non-Small-Cell Lung (drug therapy, pathology); Lung Neoplasms (drug therapy); Interleukin-2; Interleukin-10; Prospective Studies; Interleukin-4 (therapeutic use); White Matter (diagnostic imaging, pathology); Protein Kinase Inhibitors (adverse effects); ErbB Receptors (genetics, therapeutic use); Mutation; Retrospective Studies

Publication Date

12-1-2023

Publication Title

Brain and behavior

E-ISSN

2162-3279

Volume

13

Issue

12

First Page

e3326

PubMed ID

38054663

Digital Object Identifier (DOI)

10.1002/brb3.3326

Link to Full Text

Share

COinS