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

Background: Non-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.

Methods: There 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.

Results: With 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).

Conclusions: First-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.

Fig. 1

Overall survival since the initiation of treatment (n = 96): The 2-year OS was 40.6 %, with a median follow-up of 26 months (range, 11–56 months), and the estimated overall survival time was 21.0 months

Fig. 2

Impact of the timing of brain RT on overall survival (p = 0.246, n = 96): 39 patients were treated initially with brain radiotherapy (first-line RT), and 23 patients were administered RT when they exhibited brain disease progression (delayed RT). Thirty-four patients did not receive radiotherapy and remained asymptomatic until the last follow-up (no brain RT). Univariate analysis revealed that the timing of brain RT was not significantly related to OS (p = 0.246)

Fig. 3

Brain metastasis progression free survival since the initiation of treatment (n = 96): 54 patients exhibited progressive brain disease after local or systemic treatment. The 2-year brain metastasis progression free survival (BM PFS) was 29.6 %, and the estimated BM PFS time was 17 months

Fig. 4

Impact of the timing of brain RT on BM PFS (p = 0.643, n = 96): Brain RT as first-line therapy was not significantly associated with BM PFS (p = 0.643, HR 0.82, 95 % CI 0.39–1.81)

Fig. 5

Impact of the timing of brain RT on brain-metastases-only patients’ overall survival (p = 0.019, n = 35): The timing of brain RT was significantly related to OS (P = 0.019). Patients with delayed brain RT had better long-term survival than the others