Association between EGFR-TKI Resistance and Efficacy of Radiotherapy for Brain Metastases from EGFR-mutant Lung Adenocarcinoma

fuente: 

1. HIDENARI HIRATA¹, 
2. KATSUMASA NAKAMURA²⇑, 
3. NAONOBU KUNITAKE¹,
4. YOSHIYUKI SHIOYAMA³, 
5. TOMONARI SASAKI², 
6. SAIJI OHGA²,
7. TAKESHI NONOSHITA¹, 
8. TADAMASA YOSHITAKE³, 
9. KAORI ASAI²,
10. KOUJI INOUE⁴, 
11. AKIRA NAGASHIMA⁵, 
12. MINORU ONO¹ and
13. HIROSHI HONDA²

1. ¹Department of Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
2. ²Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
3. ³Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
4. ⁴Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
5. ⁵Department of Respiratory Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

Abstract

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.