This was a prospective, observational study of health-related quality of life (HRQOL) in advanced non-small-cell lung cancer, to examine the effect of baseline brain metastasis (BBM) over 1 year of follow-up. Assessed HRQOL on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and other measures across 1100 surveys from 145 patients. Results showed greater deterioration on most measures for patients with BBM. In these, the average 1-year deterioration in patients with BBM was 19.4%. Introduction: Health-related quality of life (HRQOL) in advanced non-small-cell lung cancer (NSCLC) might be affected by the presence of brain metastasis (BM). We report findings from a prospective observational study that examined HRQOL in patients newly diagnosed with advanced NSCLC, with or without baseline BM, through 1 year of follow-up. Patients and Methods: Patients starting first-line treatment of stage IIIB/IV NSCLC were prospectively enrolled and consented at 34 US-based community oncology practices. Data on patient-reported outcomes (PROs) were collected once per cycle during treatment, and at each visit after discontinuation. PROs included the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer Module (QLQ-LC13), the Lung Cancer Module of the M.D. Anderson Symptom Inventory (MDASI-LC), and the Rotterdam Activity Level Scale (RALS). Linear mixed models were used to examine the effect of baseline BM, including differences in change over time. Results: One hundred forty-five patients provided follow-up PRO data, comprising 1100 individual surveys and 32 PRO end points. The patient group was 58.6% (n = 85) male, and 86.2% (n = 125) Caucasian. Patients with baseline BM were younger (61.3 vs. 65.8 years; P = .040) with more concurrent radiotherapy (59.4% [n = 19] vs. 15.9% [n = 18]; P < .0001). Results showed minimal differences in baseline HRQOL. Of the 20 measures that showed significant group differences in HRQOL over time, 18 showed greater deterioration for patients with baseline BM. These 18 measures included all QLQ-C30 composite measures except Global Health Status, all MDASI-LC measures, and the RALS (all P < .05). For these measures, the average 1-year deterioration in patients with baseline BM was 19.4%. Conclusion: Newly diagnosed advanced NSCLC patients with baseline BM experienced a significantly faster and clinically meaningful deterioration in PRO-based HRQOL compared with those without baseline BM. (C) 2017 Elsevier Inc. All rights reserved.