Gamma Knife consolidation therapy improves prognosis in patients with advanced epidermal growth factor receptor-mutant lung adenocarcinoma treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors.

Non-small cell lung carcinoma (NSCLC) accounts for most cancer-related deaths. Whilst epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective in prolonging the survival of patients with EGFR mutations, resistance to these therapies inevitably emerges. The present study aimed to analyze the efficacy and safety of combining Gamma Knife therapy and first-generation EGFR-TKIs treatment in patients with advanced EGFR-mutant NSCLC. The present study was a retrospective analysis performed at a single center. The patients included in the analysis were histologically confirmed as inoperable stage III or IV lung adenocarcinoma with EGFR-sensitive mutations (19DEL or 21L858R). Patients received first-generation EGFR-TKIs treatment, including gefitinib, erlotinib and icotinib, then received Gamma Knife consolidation therapy for the treatment of residual lesions in the chest, with a total of 10-17 sessions administered five times a week. Each session delivered a fractionated dose between 3.0-5.5 Gy. The primary endpoint was progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were objective response rate (ORR) and safety. Between October 2014 and November 2021, the 35 patients included in the follow-up analysis received Gamma Knife therapy combined with EGFR-TKIs treatment, with a follow-up visit in December 2023. The PFS and median OS were 20 (range, 17.6-22.4) and 39 (range, 32.0-46.0) months, respectively. The ORR was 77% and the incidence of grade III or higher radiation pneumonitis was 3%. Univariate analysis indicated an improved survival trend for patients with the following characteristics: Aged ≥62 years, carcinoembryonic antigen (CEA) level of <10 ng/ml and those with grade I or no radiation pneumonia; however, the differences were not statistically significant. Multivariate analysis demonstrated that non-smoking patients, those with a CEA level of <10 ng/ml, grade I or no radiation pneumonitis after treatment and those treated with icotinib had a statistically longer PFS. In conclusion, combining first-generation EGFR-TKIs with Gamma Knife therapy can delay EGFR resistance, extend PFS and OS, and result in a low incidence of toxic and side effects. However, further prospective randomized controlled studies are required to validate the results of the present study.