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Abstract

PURPOSE:

We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis.

PATIENTS AND METHODS:

A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling.

RESULTS:

Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001).

CONCLUSION:

Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease. 

Author information

Johung KL1, Yeh N1, Desai NB1, Williams TM1, Lautenschlaeger T1, Arvold ND1, Ning MS1, Attia A1, Lovly CM1, Goldberg S1, Beal K1, Yu JB1, Kavanagh BD1, Chiang VL1, Camidge DR1, Contessa JN2.​

1Kimberly L. Johung, Sarah Goldberg, James B. Yu, Veronica L. Chiang, and Joseph N. Contessa, Yale University School of Medicine, New Haven, CT; Norman Yeh, Brian D. Kavanagh, and D. Ross Cambidge, University of Colorado Comprehensive Cancer Center, Aurora, CO; Neil B. Desai and Kathryn Beal, Memorial Sloan Kettering Cancer Center, New York, NY; Terence M. Williams and Tim Lautenschlaeger, Ohio State University, Columbus, OH; Nils D. Arvold, Dana-Farber/Brigham and Women's Hospital, Boston, MA; and Matthew S. Ning, Albert Attia, and Christine M. Lovly, Vanderbilt University School of Medicine, Nashville, TN.

2Kimberly L. Johung, Sarah Goldberg, James B. Yu, Veronica L. Chiang, and Joseph N. Contessa, Yale University School of Medicine, New Haven, CT; Norman Yeh, Brian D. Kavanagh, and D. Ross Cambidge, University of Colorado Comprehensive Cancer Center, Aurora, CO; Neil B. Desai and Kathryn Beal, Memorial Sloan Kettering Cancer Center, New York, NY; Terence M. Williams and Tim Lautenschlaeger, Ohio State University, Columbus, OH; Nils D. Arvold, Dana-Farber/Brigham and Women's Hospital, Boston, MA; and Matthew S. Ning, Albert Attia, and Christine M. Lovly, Vanderbilt University School of Medicine, Nashville, TN. joseph.contessa@yale.edu.