DFS and OS analyses were performed in 159 patients (multiple GGNs [n=34] vs Single lesion [n=125]). Dominant tumors were divided into three categories (Pure GGN, Part solid and Solid). Patients with multiple GGNs were divided into pure [n=5], partly solid [n=20] and solid[n=9). Patients with a single lesion were divided into pure [n=17], partly solid[n=40] and solid[n=68) (Figure 1). The patient and surgical characteristics are summarized in Table 1. There were 159 patients (multiple GGN [n=34], pure GGN [n=17], part solid [n=40] and solid [n=68]). Five years of follow-up was completed in all cases. All patients were Asians and underwent video-assisted thoracoscopic resections. Combined resection of multiple lesions was performed for 23% of the patients in the multiple GGN group. Twenty percent of the patients underwent wedge resection alone. Fatal complications occurred in 2 patients in the solid group due to pulmonary embolism and a pulmonary artery rupture. Histologically, no invasive cancer was found in the Pure GGN group. Chemotherapy was performed according to the DT tumor size (pStage). There were three patients with pStage IIa disease in the multiple GGN group who did not receive chemotherapy.
Table 2 lists the results of postoperative surveillance. There were 17 cases of postoperative recurrence (multiple [n=2], part solid [n=3], and solid [n=12]). Eleven of them were positive for epidermal growth factor receptor (EGFR) mutations. The OS decreased as the C/T ratio increased (pure GGN, 94.1%; part solid, 90%; solid, 75%; Table2).
Kaplan-Meier analyses (Figure 2A) were performed to compare the patients with multiple lesions to those with single lesions; their survival did not differ to a statistically significant extent (single, 82.4% vs. multiple, 88.2%; P=0.3602). There when the outcomes were compared according to the DT classifications (Pure GGN, 94.1% vs. multiple GGN [pure], 100%; part solid, 90% vs. multiple GGN [part], 90%; solid, 75% vs. multiple GGN [solid]: 77.8%; Figure 2B–D). The DFS was similar to the OS (Figure 3).
Characteristics of the DT and non-dominant GGNs in the multiple GGN group
Characteristics of the DT and the non-dominant GGN are summarized in Table 3. As for non-dominant GGN, there were 2 cases with very large numbers of nodules (46 and 18) in the part solid group; these cases were excluded as outliers. Radiographically, the mean diameters of the DTs were as follows: Pure GGN, 8.6±4.6 mm; part solid, 21.7±11.6 mm; and solid, 36.8±11.2 mm. The mean diameters of the largest non-dominant GGN at presentation were as follows: pure GGN, 8.1±1.8 mm; part solid, 8.2±5.2 mm; and solid, 17.5±11.7 mm. The numbers of with non-dominant GGNs were as follows: pure GGN (range, 1-2), n=8; part solid (range, 1–7), n=38; and solid (range, 1-5), n=17. Four pure GGNs (50%), 19 part solid GGNs (50%) and 9 solid GGNs (53%) were identified in the contralateral lung to the DT. Some of the lesions in the lung lobe that differed from the DT could not be resected. Twenty-six patients had unresected GGNs. Two patients were excluded due to an extremely large numbers of unresected GGNs (n=46 and 18). Finally, 24 patients were included in the unresected GGNs analysis. In 10 of these patients, disease progression was observed in the unresected GGNs (Figure 4). In 2 cases, additional surgery or SRT was performed to treat the unresected GGN. Most unresected GGNs were pure GGN and none had a C/T ratio of >0.5.
Characteristics of the patients with GGN progression
The characteristics of the patients with or without progression of GGN are summarized in Table 4. The mean size of the unresected GGNs in the any GGN progression group was predominantly larger than that in the other group (mean size, 10.3±5.2 mm vs. 6.5±4.3 mm, respectively P=0.0004). The OS curve of the cases with and without GGN progression did not differ to a statistically significant extent (80% vs. 92.9%, P=0.3870).
The transition of the size of the 38 unresected GGNs on CT is shown in Figure5A. Twelve GGNs fulfilled the growth condition. Among them, 10 GGNs showed a change in size changed within 3 years. It took four years for all lesions change in size. The tumors of the GGNs that changed in size were significantly larger than no growth tumors (mean size 11.7±5.8 mm vs. 6.9±3.8 mm, P=0.0003) （Figure5B）.