Abstract

Although cranial radiotherapy is considered the standard treatment for brain metastasis (BM), EGFR tyrosine kinase inhibitors (TKIs) have shown promising activity in EGFR mutant non-small cell lung cancer (NSCLC) patients with BM. However, the efficacy of sequential cranial radiotherapy in patients with EGFR mutant NSCLC who are treated with EGFR TKIs remains to be determined. Patients with NSCLC who harbored an EGFR mutation and whose BM had been treated with EGFR TKIs were retrospectively reviewed. The clinical outcomes of patients treated with EGFR TKIs alone and those treated with cranial radiotherapy followed by EGFR TKIs (additive therapy) were compared. Of the 573 patients with NSCLC with BM who harbored an EGFR mutation and had received EGFR TKIs, 121 (21.1 %) had BM at the time of initial diagnosis. Fifty-nine (49 %) patients were treated with additive therapy, whereas 62 (51 %) patients were treated only with EGFR TKIs. No significant differences were observed between the additive therapy group and the EGFR TKI alone group regarding intracranial progression-free survival (PFS) (16.6 vs 21.0 months, p = 0.492) or extracranial PFS (12.9 vs 15.0 months, p = 0.770). The 3-year survival rates were similar in both groups (71.9 vs 68.2 %, p = 0.675). Additive therapy consisting of cranial radiotherapy followed by EGFR TKI treatment did not improve OS or intracranial PFS compared with EGFR TKI treatment alone in EGFR mutant NSCLC patients with BM. Further prospective studies are needed to determine the precise benefits of sequential cranial radiotherapy in EGFR mutant NSCLC treated with EGFR TKIs.Electronic supplementary materialThe online version of this article (doi:10.1007/s12032-016-0811-3) contains supplementary material, which is available to authorized users.

Highlights

  • 20–40 % of all patients with non-small cell lung cancer (NSCLC) present with brain metastasis (BM) at the time of diagnosis or develop BM during their disease course [1, 2]

  • The clinical outcomes of patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) alone and those treated with cranial radiotherapy followed by EGFR TKIs were compared

  • The longer survival achieved with effective treatments such as EGFR tyrosine kinase inhibitors (TKIs) in EGFR mutant NSCLC is associated with a higher incidence of brain metastasis during the disease course

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Summary

Introduction

20–40 % of all patients with non-small cell lung cancer (NSCLC) present with brain metastasis (BM) at the time of diagnosis or develop BM during their disease course [1, 2]. The incidence of BM in patients with epidermal growth factor receptor (EGFR) mutant advanced NSCLC is higher than in patients with wild type EGFR over the disease course [3]. The longer survival achieved with effective treatments such as EGFR tyrosine kinase inhibitors (TKIs) in EGFR mutant NSCLC is associated with a higher incidence of brain metastasis during the disease course. Whole brain radiation therapy (WBRT) has been considered the standard treatment for BM, but usually results in neurologic sequelae such as neurocognitive dysfunction. Stereotactic radiosurgery (SRS) is a novel technique that is usually indicated in patients with oligo-brain metastasis. This technique reduces the radiation damage to the

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