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Published on: August 11, 2017
Changes of Brain Structure in Patients With Metastatic Non-Small Cell Lung Cancer After Long-Term Target Therapy With
Beisheng Yang1, Chunli Luo2,3, Min Yu2
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.
Purpose:
Epidermal 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.
Method:
The 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.
Results:
The 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).
Conclusions:
An 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.
Insights
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy for metastatic non-small cell lung cancer (NSCLC) may cause brain changes. Long-term treatment showed increased white matter lesions and gray matter volume loss, suggesting a potential side effect.
Area of Science:
- Neuroscience
- Oncology
- Radiology
Background:
- Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is standard for metastatic non-small cell lung cancer (NSCLC) with EGFR mutations.
- Patients on EGFR-TKI therapy have reported cognitive decline, necessitating investigation into potential neurological side effects.
Purpose of the Study:
- To evaluate brain structural changes, specifically white matter lesions (WML) and gray matter volume (GMV), in patients with metastatic NSCLC undergoing EGFR-TKI treatment.
- To understand the potential link between EGFR-TKI therapy and observed cognitive symptoms.
Main Methods:
- Retrospective review of 75 metastatic NSCLC patients treated with EGFR-TKI from 2010-2017.
- Assessment of WML using the modified Scheltens Visual Scale and GMV using voxel-based morphometry.
Main Results:
- Significant increases in WML scores were observed at 12 and 24 months compared to baseline.
- A notable loss of GMV was detected in the right and left occipital lobes and left basal ganglia.
- Higher WML scores at 24 months were associated with younger age and female sex.
Conclusions:
- Long-term EGFR-TKI treatment in metastatic NSCLC patients is associated with increased WML and GMV loss.
- These structural brain changes may represent an unrecognized side effect of EGFR-TKI therapy.
- Further prospective studies are required to validate these findings and elucidate the underlying mechanisms.
