Clinical research on stereotactic radiosurgery combined with epithermal growth factor tyrosine kinase inhibitors in the treatment of brain metastasis of non-small cell lung cancer.

Purpose: To compare the clinical efficacy and safety of stereotactic radiosurgery (SRS) combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) versus whole-brain radiation therapy (WBRT) combined with EGFR-TKIs in the treatment of brain metastasis of non-small cell Lung cancer (NSCLC).

Methods: The clinical data of patients with brain metastatic NSCLC who had EGFR-sensitive mutation and followed between January 2014 and January 2016 was retrospectively analyzed. Patients were divided into two groups according to their treatment types. Fifty seven patients were treated with SRS combined with EGFR-TKIs, while another 57 patients were treated with WBRT combined with EGFR-TKIs. The clinical efficacy, intracranial progression-free survival (iPFS), systemic progression-free survival (sPFS), overall survival (OS,) and adverse reactions were compared between the two groups. Computed tomography (CT) or magnetic resonance imaging (MRI) were used for imaging evaluation in both groups and all patients underwent symptomatic treatment such as dehydration or hormone therapy according to the patient's condition. The efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) and adverse reactions were assessed based on the criteria for toxic reaction of anti-cancer drugs of WHO.

Results: There were no statistically significant differences in general conditions between the two groups of patients. The median iPFS and median sPFS were similar between the two groups (12.2 months vs. 11.5 months and 10.7 months vs. 9.8 months respectively, p>0.05). The median OS of patients treated with SRS + EGFR-TKIs was significantly longer than in those treated with WBRT + EGFR-TKIs (25.1 months vs. 22.0 months, respectively, p=0.042). No statistically significant differences were found in the objective response rate (ORR), disease control rate (DCR), the incidence rates of cytopenia, gastrointestinal reaction and liver dysfunction between the two groups (p>0.05). There were 8 cases with radiotherapy-associated grade 3 or higher brain damage in SRS + EGFR-TKIs group compared to 19 cases in those treated with WBRT + EGFR-TKIs, suggesting that the incidence rate of radiation-induced brain injuries in SRS + EGFR-TKIs group was remarkably lower than those in WBRT + EGFR-TKIs group (p=0.026).

Conclusion: The clinical efficacy of SRS combined with EGFR-TKIs is comparable to that of WBRT combined with EGFR-TKIs in the treatment of NSCLC patients with ≤3 brain metastases and EGFR-sensitive mutation and the OS of patients is longer, with lower toxic side effect and higher safety, hence SRS combined with EGFR-TKIs should be used as the preferred therapeutic regimen.