Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naive Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer from the Perspective of Long-Term Radiation Brain Damage: A Multi-Institutional Real-World Analysis

Abstract

Objective: To investigate the relationship between the timing of SRS intervention and the complications of cerebral radiation necrosis(CRN) and its impact on the cognitive function and quality of life (QOL) in patients with brain metastases of EGFR-mutated NSCLC who received TKI treatment. Methods: A total of 361 targets from 257 patients with brain oligo-metastases of EGFR-mutated NSCLC who received Cyberknife treatment between 2010 and 2017 were collected from three Cyberknife centers. The difference in brain necrosis between patients with or without TKI application was statistically counted. Logistic regression analysis was used to analyze the effect of applying TKI on the occurrence of CRN in patients, and the effect of SRS before and after TKI resistance on CRN. The effects of CRN on the cognitive function and quality of life of surviving patients were analyzed. Results: The rate of CRN in the TKI group was significantly higher than that in the non-TKI group. The incidence of brain necrosis in patients undergoing SRS after drug resistance was significantly higher than that in patients undergoing SRS before drug resistance. Regression analysis showed that combination of TKI with SRS, and SRS after TKI resistance were important influencing factors for CRN. The follow-up results of currently surviving patients showed that the occurrence of brain necrosis seriously affected the cognitive function and QOL of patients. Conclusion: Long-term radiation-induced brain damage needs to be seriously monitored in NSCLC patients with EGFR mutation brain metastasis undergoing combination of radiotherapy and TKI. Clinicians need to pay attention to this problem and make reasonable recommendations for radiotherapy and TKI treatment. Funding Statement: This Paper was supported by Clinical key project of Peking University Third Hospital (BYSY2017030). Declaration of Interests: We declared that there were no any financial and personal relationships with other people or organizations that could inappropriately influence the work. Ethics Approval Statement: The study was approved by the Ethics Committee of the Peking University Third Hospital and completed under its supervision. It was in accordance with all the ethical requirements.