Growth dynamics of lung nodules: implications for classification in lung cancer screening

Lung nodules observed in cancer screening are believed to grow exponentially, and their associated volume doubling time (VDT) has been proposed for nodule classification. This retrospective study aimed to elucidate the growth dynamics of lung nodules and determine the best classification as either benign or malignant. Data were analyzed from 180 participants (73.7% male) enrolled in the I-ELCAP screening program (140 primary lung cancer and 40 benign) with three or more annual CT examinations before resection. Attenuation, volume, mass and growth patterns (decelerated, linear, subexponential, exponential and accelerated) were assessed and compared as classification methods. Most lung cancers (83/140) and few benign nodules (11/40) exhibited an accelerated, faster than exponential, growth pattern. Half (50%) of the benign nodules versus 26.4% of the malignant ones displayed decelerated growth. Differences in growth patterns allowed nodule malignancy to be classified, the most effective individual variable being the increase in volume between two-year-interval scans (ROC-AUC = 0.871). The same metric on the first two follow-ups yielded an AUC value of 0.769. Further classification into solid, part-solid or non-solid, improved results (ROC-AUC of 0.813 in the first year and 0.897 in the second year). In our dataset, most lung cancers exhibited accelerated growth in contrast to their benign counterparts. A measure of volumetric growth allowed discrimination between benign and malignant nodules. Its classification power increased when adding information on nodule compactness. The combination of these two meaningful and easily obtained variables could be used to assess malignancy of lung cancer nodules.