We report on 63 subjects with NSCLC and lung tumors that were amenable to segmentation by the VITAL/VITREA 2 algorithm. These cancers represent 42% of the lung cancers detected to date as part of the ongoing PLuSS (). The 63 subjects with NSCLC included in the analysis and the 65 subjects with NSCLC excluded from analysis were similar with respect to sex, age, race, smoking history, lung function (GOLD), and a CT measure of emphysema (). The group excluded from analysis contained more non-AC/BAC, more NSCLC diagnosed at advanced stage (III/IV), and more subjects dying before the end of follow-up. By requiring two CT scans separated by more than 90 days, the DT calculation effectively excluded lung cancer presenting as a large primary tumor, as a central airway abnormality, or as a tumor with lymph node enlargement at screening. This situation, accounting for 29 of 65 excluded cases, appropriately demanded more immediate biopsy intervention and explained the histology, stage, and outcome differences observed between cases excluded and included for DT analysis.
Two factors—histology and manner of detection—differed by DT. AC/BAC histology and prevalent detection characterized cases with slow DT (). Equivalently, AC/BAC histology and prevalent cases had longer DT ().
Other studies have looked at DTs in lung cancer (6
). Several studies have compared DT in squamous cell carcinoma (SCC) and AC, showing significantly shorter DT in SCC than in AC (6
). Hasegawa and associates reported on DT in early-stage SCC versus AC in a CT screening–detected population from Japan (6
). They reported mean DTs for 8 SCC versus 49 AC of 97 versus 533 days. There is one study that showed no significant difference among histologic types of lung cancer and DT; this study included 21 of 149 subjects (14%) that did not grow between the two CT scans (10
). Our study is the first to compare prevalent and nonprevalent NSCLC. In light of the recently announced results from the NLST, it is likely that screening CT scans in high-risk individuals will become much more mainstream. If this occurs, many more lung nodules will be found that will require follow-up. The risks of finding indeterminant pulmonary nodules in high-risk individuals include morbidity from overly aggressive diagnostic procedures and radiation exposure from follow-up imaging (2
). Tools that allow enhanced prediction of individual lung cancer risk will be critical to the management of CT-detected lung nodules. We and others have published clinical predictive formulas for individual lung cancer risk (11
). The use of DT data for indeterminate peripheral lung nodules could potentially aid in the risk stratification and follow-up management.
A study by van Klaveren and colleagues has advocated using DT to predict benign versus malignant lung nodules detected on CT screening (14
). Focusing on nodules 50 to 500 mm3
, these authors report that a DT > 400 days on a follow-up CT scan at 3 months had a point estimate negative predictive value of 99.7%. These data are relevant to indeterminant small pulmonary nodules in a CT screening population. Our data focus on screening-detected lung cancers and show a wide range of DTs (72–4,263 d). Our results are similar to Hasegawa (6
) with respect to slower DT for AC. We also found slower DT in prevalent cancers, the majority of which (34/42 [81%]) were ACs (). The slower DT in prevalent lung cancers is not unexpected. Compared with cancer detected shortly after an initially normal screening, the pool of cases found at an initial screening typically includes a higher proportion of slower-growing prevalent tumors existing in the population for longer and indefinite periods of time. One could argue that the more rapid DT in nonprevalent cancers should be a factor that informs the management of newly detected lung nodules on follow-up CT scans done serially in high-risk patients. It is known that new nodules not previously seen on prior CT scans are more likely to be cancer than indeterminant nodules of unknown duration. Thus, the management of these nodules should be more expectant with shorter-interval follow-up and a lower threshold to biopsy. With respect to using DT data for peripheral indeterminant lung nodules of unknown duration, our data suggest that following nodules detected on prevalence CT scans for 2 years may be inadequate (15
). shows that 25% of ACs had a DT > 711 days, suggesting that there is a wide range of growth rates for this type of lung cancer. One can hypothesize that in slow-growing prevalent nodules suggestive of adenocarcinoma there is the potential for overdiagnosis and therefore a more conservative diagnostic management approach might be considered in selected patients.
There are reports that CT slice thickness and type of software package can affect the accuracy of volumetric measurements, especially for small (< 10 mm) nodules (16
). To minimize this effect, it has been suggested to use the same section thickness and overlap and the same segmentation software for all studies, a protocol we adhered to. In our experience, the VITREA/VITAL nodule segmentation software appears to be robust to slice thickness and other image acquisition parameters. Nodule characteristics (e.g., central location or proximity to vessels or airways), not technical parameters (e.g., slice thickness), explained our inability to segment the nine nodules excluded from volumetric analysis.
We have presented DT data on lung cancer appearing in PLuSS, a study using CT to detect early lung cancer. Using currently available technology, only 63 of 148 (43%) of all lung cancer and 63 of 128 (49%) of NSCLCs were amenable to DT analysis. AC/BAC comprised 46 of 63 (73%) of cancer amenable to DT analysis but 26 of 30 (87%) with slow DT. Squamous cell cancers comprised 8 of 63 (13%) of cancers amenable to DT analysis but 6 of 10 (60%) with rapid DT. Prevalent cancers had significantly slower DT than nonprevalent cancers. These results are most applicable to peripheral indeterminant nodules that are suitable for follow-up with serial CT scan, in contrast to more suspicious nodules that are more appropriate for immediate biopsy. As the field of quantitative CT analysis evolves with improved software and computerized segmentation algorithms incorporating freehand sketching of nodules into automated segmentation, volumetric nodule analysis will be easier and more reproducible. We believe the results presented in this manuscript represent a tip-of-the-iceberg phenomenon with respect to quantitative CT analysis of lung nodules, with future studies incorporating new radiology informatics and imaging biomarkers. If the promise of the NLST is to be fulfilled, the many indeterminant lung nodules detected by CT screening will call for a more standardized approach to their clinical management. These results should affect the management of peripheral indeterminant lung nodules detected on screening CT scans.