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Abstract

Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

Fig 1.

Kaplan-Meier analysis comparing overall survival in patients treated with upfront stereotactic radiosurgery (SRS), upfront whole-brain radiotherapy (WBRT), and upfront epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI).​ 

Author information​

Magnuson WJ1, Lester-Coll NH1, Wu AJ1, Yang TJ1, Lockney NA1, Gerber NK1, Beal K1, Amini A1, Patil T1, Kavanagh BD1, Camidge DR1, Braunstein SE1, Boreta LC1, Balasubramanian SK1, Ahluwalia MS1, Rana NG1, Attia A1, Gettinger SN1, Contessa JN1, Yu JB1, Chiang VL1.

1 William J. Magnuson, Nataniel H. Lester-Coll, Scott N. Gettinger, Joseph N. Contessa, James B. Yu, and Veronica L. Chiang, Yale School of Medicine, New Haven, CT; Abraham J. Wu, T. Jonathan Yang, Natalie A. Lockney, Naamit K. Gerber, and Kathryn Beal, Memorial Sloan Kettering Cancer Center, New York, NY; Arya Amini, Tejas Patil, Brian D. Kavanagh, and D. Ross Camidge, University of Colorado School of Medicine, Denver, CO; Steven E. Braunstein and Lauren C. Boreta, University of California-San Francisco, San Francisco, CA; Suresh K. Balasubramanian and Manmeet S. Ahluwalia, Cleveland Clinic Foundation, Cleveland, OH; and Niteshkumar G. Rana and Albert Attia, Vanderbilt University School of Medicine, Nashville, TN.