Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis.

Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, Ning MS, Attia A, Lovly CM, Goldberg S, Beal K, Yu JB, Kavanagh BD, Chiang VL, Camidge DR, Contessa JN
J Clin Oncol. 2016 34 (2): 123-9

PMID: 26438117 · PMCID: PMC5070549 · DOI:10.1200/JCO.2015.62.0138

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.

© 2015 by American Society of Clinical Oncology.

MeSH Terms (34)

Adult Aged Anaplastic Lymphoma Kinase Antineoplastic Agents Brain Neoplasms Carbazoles Carcinoma, Non-Small-Cell Lung Cranial Irradiation Crizotinib Disease-Free Survival Female Follow-Up Studies Gene Rearrangement Humans Kaplan-Meier Estimate Karnofsky Performance Status Lung Neoplasms Male Middle Aged Molecular Targeted Therapy Neoplasm Staging Piperidines Prognosis Protein-Tyrosine Kinases Protein Kinase Inhibitors Pyrazoles Pyridines Pyrimidines Radiosurgery Receptor Protein-Tyrosine Kinases Risk Assessment Risk Factors Smoking Sulfones

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