Changes of Brain Structure in Patients With Metastatic Non-Small Cell Lung Cancer After Long-Term Target Therapy With EGFR-TKI.

Beisheng Yang,Yongmei Liu,Min Yu,Lin Zhou,Youling Gong,Yong Xu,Ying Zhou,Xiaojuan Zhou,Yan Zhang,Meijuan Huang,Zhiping Li,Yongsheng Wang,Su Lui,Chunli Luo,Jianxin Xue,Yanying Li,Jiang Zhu,Bo Tao,Bing Tang ,Feng Peng ,You Lü

doi:10.3389/fonc.2020.573512

Abstract

PurposeEpidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is the routine treatment for patients with metastatic non-small cell lung cancer (NSCLC) harboring positive EGFR mutations. Patients who undergo such treatment have reported cognitive decline during follow-up. This study, therefore, aimed to evaluate brain structural changes in patients receiving EGFR-TKI to increase understanding of this potential symptom.MethodThe medical records of 75 patients with metastatic NSCLC (without brain metastasis or other co-morbidities) who received EGFR-TKI therapy from 2010 to 2017 were reviewed. The modified Scheltens Visual Scale and voxel-based morphometry were used to evaluate changes in white matter lesions (WML) and gray matter volume (GMV), respectively.ResultsThe WML scores were higher at the 12-month [8.65 ± 3.86; 95% confidence interval (CI), 1.60–2.35; p < 0.001] and 24-month follow-ups (10.11 ± 3.85; 95% CI, 2.98–3.87; p < 0.001) compared to baseline (6.68 ± 3.64). At the 24-month follow-up, the visual scores were also significantly higher in younger patients (3.89 ± 2.04) than in older patients (3.00 ± 1.78; p = 0.047) and higher in female patients (3.80 ± 2.04) than in male patients (2.73 ± 1.56; p = 0.023). Additionally, significant GMV loss was observed in sub-regions of the right occipital lobe (76.71 voxels; 95% CI, 40.740–112.69 voxels), left occipital lobe (93.48 voxels; 95% CI, 37.48–149.47 voxels), and left basal ganglia (37.57 voxels; 95% CI, 21.58–53.57 voxels) (all p < 0.005; cluster-level false discovery rate < 0.05).ConclusionsAn increase in WMLs and loss of GMV were observed in patients with metastatic NSCLC undergoing long-term EGFR-TKI treatment. This might reflect an unknown side-effect of EGFR-TKI treatment. Further prospective studies are necessary to confirm our findings.

Highlights

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide
Fortyone (54.7%) and 34 (45.3%) patients were positive for epidermal growth factor receptor (EGFR) 19 exon deletion and 21 exon L858R transformation, respectively
For the 21 patients included in the gray matter volume (GMV) analysis, the median age was 59 years and the majority were female (12/21, 57.1%) (Table 1)

Summary

Introduction

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. About 40–50% of Asian patients with NSCLC harbor epidermal growth factor receptor (EGFR) mutations, and distant metastases are observed in nearly 40% of these patients at initial diagnosis [1]. The approval of gefitinib, the first-generation EGFR tyrosine kinase inhibitor (TKI), led to the development of molecular targeted therapy for lung cancer [2]. Prospective phase III trials have established that EGFR-TKIs are superior to chemotherapy for patients harboring an EGFR mutation [3,4,5,6]. EGFR-TKIs have been recommended as first-line treatment for such patients in clinical guidelines [7, 8]. EGFR-TKI therapy has been routinely prescribed for patients with EGFR mutations worldwide

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