Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non–small cell lung cancer and brain metastases

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  • 1 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital;
  • 2 Department of Radiology, Taipei Veterans General Hospital;
  • 3 School of Medicine, National Yang-Ming University, Taipei;
  • 4 Cancer Center, Taipei Veterans General Hospital;
  • 5 Department of Chest Medicine, Taipei Veterans General Hospital;
  • 6 Brain Research Center, National Yang-Ming University, Taipei;
  • 7 Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University; and
  • 8 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
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OBJECTIVE

The presence of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).

METHODS

This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.

RESULTS

The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).

CONCLUSIONS

The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

ABBREVIATIONS BM = brain metastasis; EGFR = epidermal growth factor receptor; GKRS = Gamma Knife radiosurgery; KPS = Karnofsky Performance Scale; NSCLC = non–small cell lung cancer; OS = overall survival; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery; TKI = tyrosine kinase inhibitor; WBRT = whole-brain radiotherapy.

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Contributor Notes

Correspondence Huai-Che Yang: Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan. wade012@gmail.com.

INCLUDE WHEN CITING Published online June 21, 2019; DOI: 10.3171/2019.4.JNS19446.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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