Brain surgery in combination with tyrosine kinase inhibitor and whole brain radiotherapy for epidermal growth factor receptor-mutant non-small-cell lung cancer with brain metastases

Abstract

The role of brain surgery (BS) on the survival of patients with non-small-cell lung cancer (NSCLC) and brain metastases (BM), particularly those with epidermal growth factor receptor (EGFR) mutations under tyrosine kinase inhibitors (TKIs) is yet to be defined. We aimed to investigate whether BS could improve the survival of patients in addition to the combination of TKIs and whole brain radiotherapy (WBRT). A cohort of 1394 NSCLC patients between 2011 and 2016 was retrospectively studied. One hundred patients with BM receiving TKI + RT were enrolled. Forty patients (40%) received TKI + BS + RT, and 60 patients (60%) received TKI + RT. Survival time was calculated from the date of BM diagnoses to the date of death or last follow-up. With a median follow-up of 25.6 months (95% CI, 18.6-35.7), the median survival after BM was 18.2 months (95% CI, 10.8 to 27.4) in the TKI + BS + RT group and 11.8 months (95% CI, 5.2 to18) in the TKI + RT group. Cox proportional hazards regression model for the patients with the largest BM over 1 cm showed that TKI + BS + RT group was associated with improved survival relative to TKI + RT group (HR, 0.49; 95% CI, 0.29 to 0.83; P = 0.008). BS adds significant survival benefits in addition to TKIs and WBRT, especially for patients with EGFR-mutant NSCLC and the largest BM over 1 cm.

Figure 1

Patient enrollment flow diagram. Survival time was calculated from the date of BM diagnoses to the date of death or last follow-up. Abbreviations: BM: brain metastasis; WBRT: whole brain radiation therapy; TKI: tyrosine kinase inhibitor; BS: brain surgery.

Figure 2

Cox regression comparing survival after the diagnosis of brain metastasis in epidermal growth factor receptor-mutant non-small-cell lung cancer patients under tyrosine kinase inhibitors treated with and without brain surgery for brain metastases before whole-brain radiation therapy.

Figure 3

Cox regression comparing survival after the diagnosis of brain metastasis in epidermal growth factor receptor-mutant non-small-cell lung cancer patients under tyrosine kinase inhibitors with a size of the largest brain metastasis over 1 cm treated with and without brain surgery for brain metastases before whole-brain radiation therapy.