title: Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kimberly 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.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Johung
authors.affiliation: Kimberly 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.
authors.forename: Norman
authors.initials: N
authors.lastname: Yeh
authors.affiliation: Kimberly 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.
authors.forename: Neil B
authors.initials: NB
authors.lastname: Desai
authors.affiliation: Kimberly 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.
authors.forename: Terence M
authors.initials: TM
authors.lastname: Williams
authors.affiliation: Kimberly 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.
authors.forename: Tim
authors.initials: T
authors.lastname: Lautenschlaeger
authors.affiliation: Kimberly 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.
authors.forename: Nils D
authors.initials: ND
authors.lastname: Arvold
authors.affiliation: Kimberly 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.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Ning
authors.affiliation: Kimberly 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.
authors.forename: Albert
authors.initials: A
authors.lastname: Attia
authors.affiliation: Kimberly 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.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lovly
authors.affiliation: Kimberly 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.
authors.forename: Sarah
authors.initials: S
authors.lastname: Goldberg
authors.affiliation: Kimberly 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.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beal
authors.affiliation: Kimberly 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.
authors.forename: James B
authors.initials: JB
authors.lastname: Yu
authors.affiliation: Kimberly 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.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kavanagh
authors.affiliation: Kimberly 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.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Chiang
authors.affiliation: Kimberly 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.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
authors.affiliation: Kimberly 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.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Contessa
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D002227:Carbazoles / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D016371:Cranial Irradiation; D000077547:Crizotinib; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009367:Neoplasm Staging; D010880:Piperidines / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016634:Radiosurgery; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013450:Sulfones / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib; C582670:alectinib