1. Boksoon Chang, MD ; Jung Hye Hwang, MD ; Yoon-Ho Choi, MD ; Man Pyo Chung, MD, PhD ; Hojoong Kim, MD, PhD, FCCP ; O Jung Kwon, MD, PhD ; Ho Yun Lee, MD ; Kyung Soo Lee, MD, PhD ; Young Mog Shim, MD, PhD ; Joungho Han, MD, PhD ; and Sang-Won Um, MD, PhD Natural History of Pure Ground-Glass Opacity Lung Nodules Detected by Low-Dose CT Scan 호흡기내과 R1. 박민아

2. Introduction The advent of low-dose CT (LDCT) scanning has altered the landscape of lung cancer screening With the increased use of LDCT scan screening for lung cancer since the 1990s, very faint and smaller lesions termed ground-glass opacities (GGOs) have been encountered more frequently GGOs are characterized as lesions of homogenous density and with hazy increase in density in the lung field that does not obscure the bronchovascular structure  found in 0.2% to 0.5% of screened populations

3. Introduction GGOs can result in a variety of differential diagnoses of benign and malignant diseases  If the GGO is due to inflammation or bleeding ; disappears during an initial 3-month follow-up  persistent focal GGOs ; correspond to focal fibrosis, atypical adenomatous hyperplasia, bronchoalveolar carcinoma, invasive adenocarcinoma Although GGOs are generally reported to grow slowly, their natural history is still unclear due to short clinical experience with them Also, suspicion exists that some focal GGOs are the result of an overdiagnosis bias

4. Introduction  Purpose elucidate the natural history of screening-detected pure GGO nodules during a long-term follow-up of >2 years in patients with no history of lung cancer or other malignancy

5. Methods - retrospectively reviewed the database for subjects who had undergone screening LDCT scans at the Center for Health Promotion, Samsung Medical Center (June 1997 and September 2006) - persistent, pure GGO lung nodules, who were followed for > 2 years after the initial LDCT scans Pateints

6. Methods  Exclusion criteria - transient GGO lung nodules, diffuse GGO lung lesions - suspicion of interstitial lung disease, fibrotic changes or bronchiolitis, a confirmed solid or mixed GGO nodule on thin section chest CT scan - a history of previous primary lung cancer - any other malignancy resection of GGO lung nodules within 2 years - failure to undergo thin-section chest CT scans( < 2.5 mm) at the initial LDCT scan or during the follow-up period. Pateints

7. Methods The definitions of pure GGO and mixed GGO nodules were based on the tumor shadow disappearance rate (TDR) - solid (TDR = 1), mixed (0 < TDR < 1), pure GGOs (TDR = 0) GGO nodule size : ≥2 mm from the size on initial screening LDCT scan growth group : patients with detection of increased size in one or more nodules non-growth group : patients with lack of nodule growth or decreased nodule size Volume doubling time : based on the sizes of the GGO nodules on the initial LDCT scan and the final chest CT scan calculated according to a modified method of the Schwartz formula Radiologic Definition of GGO Nodules

8. Results

12. Growth patterns of GGO nodules One nodule had insufficient follow-up CT scans for the growth pattern analysis. one (9.1%) exhibited a linear growth pattern without dormancy, but 10 (90.9%) were dormant for >12 months and subsequently grew

13. Results 72.7 % 27.3 %

14. Discussion Previous studies of the natural history of GGO lung nodules have had limitations, including a short follow-up period, a small number of patients, heterogeneous populations that included patients with a history of malignancy, populations that included both pure and mixed GGO nodules, and populations that included only patients who had undergone surgical resection  a history of lung cancer appears to be a risk factor for GGO growth  the GGO lung nodules in patients with extrapulmonary malignancies tended to display a high malignancy rate One strength of this study was the long-term follow-up evaluation of a relatively large number of patients without a history of lung cancer

15. Discussion 5 patients with mixed GGO nodules were excluded from the analysis  The frequency and rate of growth were higher for mixed GGO nodules than for pure GGO nodules The results of our study support recent guidelines recommending that pure GGO nodules > 10 mm should be considered for surgical resection, as they have a high risk for growth Pure GGOMixed GGO Frequency of GGO growth13.5%60% Volume doubling time769 days488 days

16. Discussion  Limitation it was performed retrospectively  the follow-up CT scan protocol and duration were heterogeneous all study patients did not undergo tissue confirmation  could not calculate the prevalence of primary lung cancer in this patient cohort the size change and volume doubling time of GGO nodules may be difficult to evaluate accurately based on a two-dimensional size measurement (GGO nodule volumetry could not be applied because of the limitation of screening LDCT scan in this study)

17. Conclusion About 90% of the screening-detected pure GGO lung nodules did not grow during long term follow-up in subjects with no history of malignancy and most of growing nodules had an indolent clinical course Nodule growth is important in differentiating those that are malignant from those that should be followed for future growth