Radiotherapy for asymptomatic brain metastasis in epidermal growth factor receptor mutant non-small cell lung cancer without prior tyrosine kinase inhibitors treatment: a retrospective clinical study

Abstract

BackgroundNon-small cell lung cancer (NSCLC) with brain metastasis (BM) harboring an epidermal growth factor receptor (EGFR) mutation shows good response to tyrosine kinase inhibitors (TKIs). This study is to assess the appropriate timing of brain radiotherapy (RT) for asymptomatic BM in EGFR mutant NSCLC patients.MethodsThere were 628 patients diagnosed with EGFR mutant NSCLC between October 2005 and December 2011. Treatment outcomes had been retrospectively evaluated in 96 patients with asymptomatic BM without prior TKI treatment. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT.ResultsWith a median follow-up of 26 months, the 2-year OS was 40.6 %. Univariate analyses revealed that ECOG performance status (p = 0.006), other distant metastases (p = 0.002) and first line systemic treatment (p = 0.032) were significantly associated with overall survival (OS). Multivariate analyses revealed that other sites of distant metastases (p = 0.030) were prognostic factor. The timing of brain RT was not significantly related to OS (p = 0.246). The 2-year BM progression-free survival (PFS) was 26.9 %. Brain RT as first-line therapy failed to demonstrate a significant association with BM PFS (p = 0.643).ConclusionsFirst-line brain RT failed to improve long-term survival in TKI-naïve EGFR mutant NSCLC patients with asymptomatic BM. Prospective studies are needed to validate these clinical findings.

Clinical study of the treatment of multiple brain metastases from adenocarcinoma of the lung by simultaneous integrated boost intensity-modulated radiotherapy

“…The factors including gender, age, radiotherapy dose in whole brain and pathological grading have no significant influence on survival. The ECOG score is higher, the poorer the prognosis will be, which is to correspondence with the previous reports [26][27][28]. The radiotherapy dose in intracranial metastases is positively related with the prognosis.…”

Clinical factors associated with mortality within three months after radiosurgery of asymptomatic brain metastases from non-small cell lung cancer

“…In fact, small, asymptomatic brain metastases respond well to TKI treatment alone in treatment naïve patients [29]. Liu et al [29] analyzed overall survival in 96 neurologically-asymptomatic, EGFR-mutant NCSLC patients with brain metastases under three treatment groups: upfront radiation therapy (RT, both WBRT and SRS), delayed RT but upfront TKI treatment, or no RT. They argued for upfront EGFR-TKI followed by RT when appropriate as they found no significant impact on OS with delayed RT.…”

Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model

“…Approximately 25–30% of NSCLC patients experience CNS metastases [20]. EGFR TKIs have become a first-line treatment for EGFR mutation-positive NSCLC patients; they are also used in NSCLC patients with brain metastases, and numerous studies have confirmed their safety and efficacy [9, 10].…”

“…Different from research exploring the mechanism of tumor transplantation and blood metastases as the object of study, this study primarily compared the efficacy of EGFR-TKIs in the treatment of intracranial tumors, for which the direct intracranial transplant method created a more consistent model. Furthermore, whether in drug efficacy studies of metastatic brain tumors or intracranial primary tumors, this type of animal model is widely applied [20, 42, 43]. Secondly, in this study, we did not investigate the potential effect of WBRT on the penetration of EGFR-TKIs into the CSF.…”