Regional Emphysema of a Non-Small Cell Tumor Is Associated with Larger Tumors and Decreased Survival

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 2950 Hounsfield units (%LAA2950) and measured for each region. Wholelung %LAA2950 was defined as the emphysema score of the entire lung parenchyma, whereas regional %LAA2950 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 %LAA2950. 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 %LAA2950 was associated with larger tumors (P = 0.024). Survival, stratified by stage, was significantly worse in those with tumor %LAA2950 greater than or equal to the 50th percentile versus less than the 50th percentile (P = 0.046). Whole-lung %LAA2950 and regional %LAA2950 (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 %LAA2950 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 nonsmall cell lung cancer tumor occurs is associated with increasing tumor size and worse overall survival.

Severity of pulmonary emphysema and lung cancer

“…[12] Many studies have been conducted to reveal the effect of emphysema on the development of lung cancer and their biological relationship. [13–15] Because of the common pathogenic process of the 2 disease entities and heterogeneous distribution of emphysema in the lungs, it has been postulated that regional severity of emphysema may determine the location of lung cancer. A few studies have shown that regional magnitude of emphysema is related to the location of lung cancer.…”

Emphysema is associated with the aggressiveness of COPD‐related adenocarcinomas

“…The impact of emphysema on the tumor aggressiveness of lung cancer in patients with COPD, not limited to adenocarcinoma, has been previously reported in the context of prognosis. Ueda et al revealed that CT‐diagnosed emphysema, but not spirometric values of airflow obstruction, was associated with worse overall and disease‐specific survival in early‐stage lung cancer, and Kinsey et al reported that the severity of peritumoral emphysema as well as the presence of emphysema affected tumor size and worse overall survival . Given the controversy regarding the prognostic impact of COPD on survival after resection of lung cancer, these results might suggest that the presence of emphysema may be more associated with regulation of the biology of lung cancer than airflow limitation itself.…”

Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non–Small Cell Lung Cancer

“…Details of enrollment and follow up of this cohort have been described previously. (14-16) Briefly, patients (>18 years old) with pathologically confirmed, newly diagnosed, NSCLC were consecutively recruited and followed at Massachusetts General Hospital between 2002 and 2006. This time period was selected in order to have adequate follow up time for analysis of overall survival.…”