1Department of Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
2Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
3Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
4Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
5Department of Respiratory Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
Aim: To clarify how patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) respond to radiotherapy (RT) for brain metastases. Patients and Methods: Forty-seven patients were divided into the following three groups: a TKI-naïve group with EGFR mutation (n=11), a TKI-resistant group with EGFR mutation (n=10), and an EGFR-wild-type group (n=26). Patients received stereotactic RT (n=23) or whole-brain RT (n=24). Results: The response rate for patients with TKI-resistant tumor at three months after RT tended to be lower (11%) than that of those who were TKI-naïve (82%, p=0.006) and for patients with wild-type EGFR (48%, p=0.10). On univariate analysis, central nervous system progression-free and overall survival were significantly shorter for patients with TKI-resistant tumors than for those who were TKI-naïve (p=0.018 and p=0.005, respectively). Multivariate analysis showed that TKI resistance was an independent predictor of poorer overall survival (p=0.011).
Conclusion: Acquired resistance to TKIs appears to be associated with low efficacy of brain RT.