C Matthew Kinsey1, Raúl San José Estépar2,3, Yongyue Wei4,5, George R Washko6, David C Christiani4,5,7. 1. 1 Division of Pulmonary and Critical Care, University of Vermont Medical Center, Burlington, Vermont. 2. 2 Department of Radiology. 3. 3 Laboratory of Mathematics in Imaging, and. 4. 4 Department of Environmental Health, and. 5. 5 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; and. 6. 6 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 7. 7 Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts.
Abstract
RATIONALE: Chronic obstructive pulmonary disease is associated with a worse overall survival in non-small cell lung cancer. Lung emphysema is one component of chronic obstructive pulmonary disease. We hypothesized that emphysema of the tumor region may result in larger tumors and a poorer overall survival. METHODS: We evaluated 304 cases of non-small cell lung cancer from a prospectively enrolled cohort. The lung was divided into equal volumetric thirds (upper, middle, or lower region). Emphysema was defined as percentage of low-attenuation areas less than -950 Hounsfield units (%LAA-950) and measured for each region. Whole-lung %LAA-950 was defined as the emphysema score of the entire lung parenchyma, whereas regional %LAA-950 was the score within that particular region (upper, middle, or lower). The emphysema score of the region in which the tumor occurred was defined as the tumor %LAA-950. Tumor diameter was measured while blinded to characteristics of the lung parenchyma. A proportional hazards model was used to control for multiple factors associated with survival. MEASUREMENTS AND MAIN RESULTS: Increasing tumor %LAA-950 was associated with larger tumors (P = 0.024). Survival, stratified by stage, was significantly worse in those with tumor %LAA-950 greater than or equal to the 50th percentile versus less than the 50th percentile (P = 0.046). Whole-lung %LAA-950 and regional %LAA-950 (e.g., regional emphysema without tumor occurring in the region) were not significantly associated with survival. There were no differences in presenting symptoms or locations of mediastinal or distant metastasis by emphysema score. Increasing tumor %LAA-950 was associated with an increased risk of death (adjusted hazard ratio, 1.36; confidence interval, 1.09-1.68; P = 0.006) after adjustment for age, sex, smoking status, histology, stage, performance status, chemotherapy, radiation, and surgery. Sensitivity analyses revealed no significant difference in the effect size or test of significance for each of the following conditions: (1) exclusion of cases with central tumor location, (2) exclusion of cases where surgery was performed, (3) exclusion of cases where radiation therapy was performed, (4) exclusion of cases where epidermal growth factor receptor tyrosine kinase inhibitors were administered, and (5) inclusion of only stage IV disease. CONCLUSIONS: Increasing emphysema of the region in which a non-small cell lung cancer tumor occurs is associated with increasing tumor size and worse overall survival.
RATIONALE: Chronic obstructive pulmonary disease is associated with a worse overall survival in non-small cell lung cancer. Lung emphysema is one component of chronic obstructive pulmonary disease. We hypothesized that emphysema of the tumor region may result in larger tumors and a poorer overall survival. METHODS: We evaluated 304 cases of non-small cell lung cancer from a prospectively enrolled cohort. The lung was divided into equal volumetric thirds (upper, middle, or lower region). Emphysema was defined as percentage of low-attenuation areas less than -950 Hounsfield units (%LAA-950) and measured for each region. Whole-lung %LAA-950 was defined as the emphysema score of the entire lung parenchyma, whereas regional %LAA-950 was the score within that particular region (upper, middle, or lower). The emphysema score of the region in which the tumor occurred was defined as the tumor %LAA-950. Tumor diameter was measured while blinded to characteristics of the lung parenchyma. A proportional hazards model was used to control for multiple factors associated with survival. MEASUREMENTS AND MAIN RESULTS: Increasing tumor %LAA-950 was associated with larger tumors (P = 0.024). Survival, stratified by stage, was significantly worse in those with tumor %LAA-950 greater than or equal to the 50th percentile versus less than the 50th percentile (P = 0.046). Whole-lung %LAA-950 and regional %LAA-950 (e.g., regional emphysema without tumor occurring in the region) were not significantly associated with survival. There were no differences in presenting symptoms or locations of mediastinal or distant metastasis by emphysema score. Increasing tumor %LAA-950 was associated with an increased risk of death (adjusted hazard ratio, 1.36; confidence interval, 1.09-1.68; P = 0.006) after adjustment for age, sex, smoking status, histology, stage, performance status, chemotherapy, radiation, and surgery. Sensitivity analyses revealed no significant difference in the effect size or test of significance for each of the following conditions: (1) exclusion of cases with central tumor location, (2) exclusion of cases where surgery was performed, (3) exclusion of cases where radiation therapy was performed, (4) exclusion of cases where epidermal growth factor receptor tyrosine kinase inhibitors were administered, and (5) inclusion of only stage IV disease. CONCLUSIONS: Increasing emphysema of the region in which a non-small cell lung cancertumor occurs is associated with increasing tumor size and worse overall survival.
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