Discriminating invasive adenocarcinoma among lung pure ground-glass nodules: a multi-parameter prediction model

Background: Patients with consistent lung pure ground-glass nodules (pGGNs) have a high incidence of lung adenocarcinoma that can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Regular follow-up is recommended for AIS and MIA, while surgical resection should be considered for IAC. This study sought to develop a multi-parameter prediction model to increase the diagnostic accuracy in discriminating between IAC and AIS or MIA. Methods: The training data set comprised consecutive patients with lung pGGNs who underwent resection from January to December 2017 at the Zhongshan Hospital. Of the 370 resected pGGNs, 344 were pathologically confirmed to be AIS, MIA, or IAC and were included in the study. The 26 benign pGGNs were excluded. We compared differences in the clinical features (e.g., age and gender), the content of serum tumor biomarkers, the computed tomography (CT) parameters (e.g., nodule size and the maximal CT value), and the morphologic characteristics of nodules (e.g., lobulation, spiculation, pleura indentation, vacuole sign, and normal vessel penetration or abnormal vessel) between the pathological subtypes of AIS, MIA, and IAC. An abnormal vessel was defined as `vessel curve" or `vessel enlargement". Statistical analyses were performed using the chi-square test, analysis of variance (ANOVA), and rank test. The IAC prediction model was constructed via a multivariate logistical regression. Our prediction model for lung pGGNs was further validated in a data set comprising consecutive patients from multiple medical centers in China from July to December 2018. In total, 345 resected pGGNs were pathologically diagnosed as lung adenocarcinoma in the validation data set. Results: In the training data set, patients with pGGNs >= 10 mm in size had a high incidence (74.5%) of IAC. The maximal CT value of IAC [-416.1 +/- 121.2 Hounsfield unit (HU)] was much higher than that of MIA (-507.7 +/- 138.0 HU) and AIS (-602.6 +/- 93.3 HU) (P<0.001). IAC was more common in pGGNs that displayed any of the following CT manifestations: lobulation, spiculation, pleura indentation, vacuole sign, and vessel abnormality. The IAC prediction model was constructed using the parameters that were assessed as risk factors (i.e., the nodule size, maximal CT value, and CT signs). The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of this model for diagnosing IAC was 0.910, which was higher than that of the AUC for nodule size alone (0.891) or the AUC for the maximal CT value alone (0.807) (P<0.05, respectively). A multicenter validation data set was used to validate the performance of our prediction model in diagnosing IAC, and our model was found to have an AUC of 0.883, which was higher than that of the AUC of 0.827 for the module size alone model or the AUC of 0.791 for the maximal CT value alone model (P<0.05, respectively). Conclusions: Our multi-parameter prediction model was more accurate at diagnosing IAC than models that used only nodule size or the maximal CT value alone. Thus, it is an efficient tool for identifying the IAC of malignant pGGNs and deciding if surgery is needed.