Abstract
BACKGROUND: The threshold value of consolidation-to-tumor ratio (CTR) for distinguishing between ground-glass opacity (GGO)-predominant and solid-predominant ground-glass nodules (GGNs) needs to be clarified, as the lack of clarity has caused the prognostic implications to remain ambiguous. This study aimed to determine the threshold value of CTR for distinguishing between GGO-predominant GGNs and solid-predominant GGNs and elucidate the prognostic implications of the solid-predominant GGNs categorized by CTR on c-stage IA lung adenocarcinoma. METHODS: Between January 2016 and October 2018, 764 c-stage IA lung adenocarcinoma cases were assembled from the First Affiliated Hospital of Chongqing Medical University. Of the 764 lesions, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were solid nodules (SNs) on thin-section computed tomography (CT). We evaluated the correlation of the 3-dimensional (3D) consolidation component volume ratio with CTR based on the coefficient of determination, r. After receiver operating characteristic (ROC) analysis of 515 GGNs, we defined the nodule with CTR >0.750 as solid-predominant GGN and the nodule with CTR ≤0.750 as GGO-predominant GGN. Subsequently, the prognosis of 439 patients who had follow-up registration was evaluated. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was employed to compare survival rates among different groups. Cox proportional hazard regression models were applied to evaluate the independent risk factors for recurrence-free survival (RFS). RESULTS: Among 764 patients, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were SNs on thin-section CT. For 515 GGNs, the 3D consolidation component volume ratio correlated well with CTR (r=0.888). CTR tended to be slightly larger than the 3D consolidation component volume ratio. A 3D consolidation component volume ratio >50% was best predicted by CTR >0.750, followed by CTR >0.549. CTR >0.750 and CTR >0.549 predicted 3D consolidation component volume ratio >50% with 85% and 99.2% sensitivity and 91.6% and 57.2% specificity, respectively. The 5-year RFS and overall survival (OS) of patients with 0.750< CTR <1 were worse than those of patients with 0≤ CTR ≤0.750 (P<0.001 and P<0.001, respectively) but better than those of patients with CTR =1 (P=0.002 and P=0.03, respectively). Carcinoembryonic antigen (CEA) >2.1 [hazard ratio (HR) =12.516, 95% confidence interval (CI): 1.729-90.598], CTR >0.750 (HR =13.934, 95% CI: 3.341-58.123), larger consolidation component size with diameter more than 20 mm (HR =1.855, 95% CI: 1.242-2.770), poorly differentiated (HR =1.622, 95% CI: 1.056-2.491), lymph node metastasis (HR =2.473, 95% CI: 1.601-3.821), and sublobar resection (HR =2.596, 95% CI: 1.701-3.962) could predict the poor prognosis. Patients with 0≤ CTR ≤0.750 receiving sublobar resection had prognoses comparable to those receiving lobar resection, whether the tumor size ≤2 cm or consolidation component size ≤3 cm. Lobar resection was superior to sublobar resection for non-small cell lung cancer (NSCLC) ≤2 cm with CTR >0.750. CONCLUSIONS: Compared to CTR =0.5, the 2-dimensional (2D) CTR =0.750 found using the 3D consolidation component volume ratio as the gold standard better differentiated between solid-predominant GGNs and GGO-predominant GGNs. CTR >0.750 was an independent risk factor associated with the poor prognosis of patients with c-stage IA lung adenocarcinoma. Sublobar resection should be cautiously adopted in GGNs with 0.750< CTR ≤1.