1. Informed consent obtained
1325 Nodules
845 Patients
1238 Nodules
795 Patients
1229 Nodules
Excluded nine resected nodules
• No review by pathology panel
• Non-lung-cancer nodules
Excluded 57 nodules/50 patients
• Nodule diameter >3 cm
• Diameter of solid component >5 mm
• Thick section CT image
• Miscellaneous
Excluded 30 nodules – Unable to evaluate part of
multiple subsolid nodules
Informed consent obtained
(April December 28, 2011)
Eligible for assessment of growth
Assessment of frequency of invasive adenocarcinomas
(As of December 27, 2013)
Here is the study’s flow diagram. We obtained informed consent for participation in the study from 845 patients with 1325 nodules between April 2009 and December 28, For the reasons listed in the upper right-hand box, we excluded 87 nodules and 50 patients. Out of the remaining 795 patients with 1238 nodules, we excluded an additional nine nodules from our invasive adenocarcinoma evaluation, as indicated in the lower right-hand box. Finally, the frequency of invasive adenocarcinoma was assessed in 795 patients with 1229 nodules.
Supplemental data 1. Flow diagram of this study.

2. Time until appearance of solid component in PGGNs (years) 0.1401
15/02/06
D >10 mm, smoker, N=62 P
0.0046
< .0001
Time until appearance of solid component in PGGNs (years)
0.1401
0.0325*
0.5465
D >10 mm, never-smoked, N=66
D ≤10 mm
never-smoked
N=312
smoker, N=165
Estimated probability
Supplemental data 3. Time until the appearance of a solid component in PGGAs according to the initial maximal diameter and smoking status. The red, green, blue, and orange curves indicate the accumulated percentages of growth of PGGNs with a maximal diameter >10 mm in smokers, PGGNs with a maximal diameter >10 mm in never-smoked patients, PGGNs with a maximal diameter ≤10 mm in smokers, and PGGNs with a maximal diameter ≤10 mm in never-smoked patients, respectively. The pairs of red and green curves, red and blue curves, and red and orange curves showed statistically significant differences. The green, blue, and orange curves did not show growth until approximately 2 years into the follow-up period. PGGN: pure ground-glass nodule, D: initial maximal diameter, *: P value was not statistically significant after Bonferroni correction.

3. Sensitivity 1 - Specificity
Supplemental data 6. Receiver operating characteristic curve analysis for differentiating AIS and MIA from invasive adenocarcinomas showed that the cutoff value of the maximal diameter of a solid component was 3.3 mm, yielding a sensitivity of 61% and a specificity of 91%.