| ). While robust and validated software for volumetric nodule measurement is not widely used at present, we anticipate that it will have an increased role in the future.
Volume doubling times for solid cancers are well established (one volume doubling corresponds to a 26% increase in diameter), with a large majority of times being in the 100–400-day range. For subsolid cancerous nodules, which represent primary adenocarcinomas, more indolent growth is the rule, with average doubling times on the order of 3–5 years (34,66). For this reason, longer initial follow-up intervals and longer total follow-up periods are recommended for subsolid nodules than for solid nodules. Emphysema and FibrosisThe presence of emphysema on a CT image is an independent risk factor for lung cancer (67). An analysis of lung cancer and emphysema in the NLST trial revealed an incidence of 25 instances of cancer per 1000 screened patients with emphysema, compared with 7.5 instances of cancer per 1000 screened patients for those without (68). Chiles et al (69) investigated the relationship between chronic obstructive pulmonary disease phenotypes and risk of cancer in indeterminate nodules detected in the NLST trial and found that emphysema-predominant chronic obstructive pulmonary disease phenotype and increasing severity of centrilobular emphysema were associated with increased risk of malignancy. Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis, is also an independent risk factor, with a hazard ratio of approximately 4.2 compared with emphysema alone (70). Age, Sex, Race, and Family HistoryThe relationship between age and lung cancer risk has been clearly established, with an accelerating increase in risk associated with advancing age. Lung cancer is still relatively rare in individuals younger than 35 years and is unusual before the age of 40 years. For each additional decade of life, lung cancer incidence increases steadily (71,72). The possible role of sex as a risk factor for lung cancer has been explored in several recent studies. Chiles et al (69) identified certain individual characteristics of female subjects in the NLST trial, such as lower educational level and lower body mass index, that were associated with an increased risk of cancer; however, the overall 6-year risk of cancer was not significantly different from that in male subjects. Boiselle (73) examined the relative risk for women and men in the same trial with solid, nonsolid, or part-solid nodules and found a significantly higher risk in women with ground-glass (nonsolid) nodules. Female sex was also found to be a risk factor in the PanCan trial, with an overall odds ratio of 1.8; however, the relationship to nodule type was not reported (7 |