| Objective:To compare the role of MSCT (multi-slice spiral computed tomography) with 18F-FDG PET/CT (positron emission tomography, PET) in the imaging diagnosis to differentiate malignant from benign solitary pulmonary nodules (SPNs) with the use of receiver operating characteristic curve (ROC) analysis, by which to probe into the clinical use of the comprehensive imaging diagnosis in the characterization of a solitary pulmonary nodule (SPN) in order to answer the problem how to select the optimal project on the single or combining use of MSCT and F-FDG PET/CT in the clinical management of solitary pulmonary nodules.Materials and Methods:A retrospective study was performed involving the patients referred for the characterization of solitary pulmonary nodule with MSCT and 18F-FDG PET/CT between February 2001 and February 2011, for whom a pathologic diagnosis or follow-up result was available. In the study,217 solitary pulmonary nodules were examined with MSCT and 98 solitary pulmonary nodules were examined with 18F-FDG PET/CT, which were confirmed pathologically by surgery and/or needle biopsy or by follow-up.The MSCT or PET/CT images were read in consensus. The MSCT images of all 217 solitary pulmonary nodules were assessed and graded by three senior radiologists on the basis of malignant likelihood of morphological and density characteristics. The PET/CT images of all 98 solitary pulmonary nodules were interpreted by three nuclear medicine physicians. The blinded interpretation of MSCT or PET/CT images was performed. The radiologists and nuclear medicine physicians were all unaware of the patient's history and PET/CT image findings or MSCT image results each other. Each observer independently read the MSCT or PET/CT images in random order. The observers were given unlimited time to view the images in each case and were allowed to vary their viewing distance. The solitary pulmonary nodules were analyzed by location, texture, axial dimension, and density or metabolic activity and visually scored on a 5-point scale from benign to malignant. According to the MSCT images, the solitary pulmonary nodules were scored as follows:1=definitely benign; 2= probably benign; 3=equivocal; 4=probably malignant; 5=definitely malignant. According to the PET/CT images, the locations of areas of abnormal tracer (18F-FDG) uptake were recorded and the degree of uptake was scored as follows:0=no uptake; 1=less than mediastinum; 2=equal to mediastinum; 3=between mediastinum and liver; 4=higher than liver. At the same time, MSCT images were evaluated and calculated the comprehensive score according to every morphological sign as follows: 1=definitely malignant likelihood; 0.5=probably or equivocal malignant likelihood; 0=definitely benign likelihood. Correspondingly, 18F-FDG PET/CT data were evaluated semi-quantitatively on the basis of the contrast ratio (CR) obtained as follows. The regions of interest (ROIs) were placed around the areas of abnormal uptake in the nodules and contra-lateral normal lung. Highest activities in the tumor ROI (T) and in the contra-lateral normal lung ROI (N) were measured. The CR was calculated by (T—N)/(T+N) in each nodule as an index of 18F-FDG uptake. In addition, the maximum standardized uptake value (SUVmax) was determined and analyzed respectively.Receiver operating characteristic curve (ROC) analysis was used to evaluate the observer's performance in differentiating malignant from benign solitary pulmonary nodules by MSCT and 18F-FDG PET/CT. According to the size of maximum diameter (D), The solitary pulmonary nodules were classified as 2.0cm<D?3.0cm and D?2.0cm. The receiver operating characteristic (ROC) curves were respectively constructed and the optimal thresholds were determined for the diagnosis of characterization with regard to solitary pulmonary nodules of 2.0cm<D?3.0cm and D?2.0cm. ROC analysis was used to evaluate the efficiency of MSCT or 18F-FDG PET/CT in differentiating malignant from benign solitary pulmonary nodules. The area under the curve (AUC) was used as an index of diagnostic efficiency with MSCT or 18F-FDG PET/CT. A statistical analysis was done according to AUC values by Z-test. In the statistical analysis, a value of P<0.05 were considered significant.The optimal thresholds were selected with Youden's index on the ROC curves. By the criterion of optimal thresholds, the solitary pulmonary nodules were defined as positive or negative. The results of MSCT and PET/CT were compared with pathological or follow-up results respectively. Positive MSCT and PET/CT findings with malignancy and benign nodules were defined as true positive (TP) and false positive (FP), respectively. Negative MSCT and PET/CT findings with malignancy and benign nodules were defined as false negative (FN) and true negative (TN), respectively. The diagnostic values of MSCT and PET/CT were assessed by calculating sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). Sensitivity was calculated as TP/TP+FN, specificity as TN/TN+FP, accuracy as TP+TN/TP+FP+TN+FN, positive predictive value as TP/TP+FP, and negative predictive value as TN/TN+FN. All data were analyzed for significance by using the x2-test, values of P<0.05 were accepted as significance.The comprehensive imaging diagnosis in the characterization of a solitary pulmonary nodule was given by combining MSCT with PET/CT images. The images were interpreted as benign or malignant in consensus. In case of concordance between MSCT and PET/CT interpretation, the classification did not differ from the MSCT and PET/CT findings. The MSCT and PET/CT images were jointly reviewed. The combining interpretation could be described with the following rules:If the MSCT score was 5 (definitely malignant), then the solitary pulmonary nodule was considered malignant, regardless of the 18F-FDG uptake. If the MSCT score was 1 (definitely benign), then the solitary pulmonary nodule was considered benign, regardless of the 18F-FDG uptake. If the MSCT score was 2,3,4 (could not affirm to be malignant or benign), then the solitary pulmonary nodule was determined the nature according to the 18F-FDG uptake as follows. The solitary pulmonary nodule was considered malignant if the PET/CT rating was 2,3,4 (moderate uptake to uptake higher than the liver) or CR?optimal thresholds, and the solitary pulmonary nodule was considered benign if the PET/CT rating was 0,1 (no uptake or uptake less than mediastinum) and CR<optimal thresholds. In these cases, the PET/CT findings overruled the MSCT findings. The diagnostic values of combining MSCT with PET/CT findings were assessed by calculating sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). All data were analyzed and compared with single PET/CT by using the x2-test, values of P<0.05 were accepted as significance.Results:There were 146 malignant nodules and 71 benign nodules in the 217 solitary pulmonary nodules which were scanned by MSCT. There were 69 malignant nodules and 29 benign nodules in the 98 solitary pulmonary nodules which were examined by 18F-FDG PET/CT. All of malignant nodules were pathologically confirmed. The benign nodules were proved pathologically or by follow-up.Using pathology and follow-up results as the reference standard, the efficiency of MSCT as to the solitary pulmonary nodules of 2.0cm<D?3.0cm excelled that as to the solitary pulmonary nodules of D?2.0cm. The efficiency of MSCT by the 5-point scale method is better as to the nodules of 2.0cm<D?3.0cm, and the efficiency of MSCT by comprehensive score was better as to the nodules of D?2.0cm. The optimal thresholds of MSCT score were respectively 3.5 and 2.5 in the solitary pulmonary nodules of 2.0cm<D?3.Ocm and D?2.0cm. The efficiency of 18F-FDG PET/CT did not have significant difference in the solitary pulmonary nodules of 2.0cm<D?3.0cm and D?2.0cm, but the semi-quantitative analysis on the basis of CR was better than the visual analysis in characterizing a solitary pulmonary nodule. The optimal thresholds of CR were 0.45 all in the solitary pulmonary nodules of 2.0cm<D?3.0cm and D?2.0cm.As to the solitary pulmonary nodules of 2.0cm<D?3.0cm, the efficiency of semi-quantitative analysis by PET/CT did not have significant difference from MSCT, but the visual analysis by PET/CT was a little inferior to MSCT. MSCT had the higher specificity (P<0.05 for PET/CT). In the solitary pulmonary nodules of D?2.0cm, the efficiency of semi-quantitative analysis and visual analysis by PET/CT was better than MSCT. The specificity of PET/CT was higher (P<0.05 for MSCT).The comprehensive imaging diagnosis by combining MSCT images with PET/CT images demonstrated a more excellent performance in classifying solitary pulmonary nodules as benign or malignant. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of combining diagnosis by MSCT and 18F-FDG PET/CT were 97.10%,93.10%,95.92%,97.10%, 93.10%(P<0.05 for PET/CT).Conclusion:With the increasing use of MSCT, more solitary pulmonary nodules are being detected. Although the majority of these nodules are benign, lung cancer constitutes an important consideration in the differential diagnosis of solitary pulmonary nodules. The goal of management is to correctly differentiate malignant from benign nodules to ensure appropriate treatment. Recent technological advances in imaging, including MSCT and PET/CT, have improved nodule characterization and surveillance. Our study found MSCT and PET/CT all have a high accuracy for characterization of solitary pulmonary nodules. The usefulness of ROC analysis was obvious in the differential diagnosis of solitary pulmonary nodules with the comprehensive imaging characteristic obtained by MSCT and PET/CT. MSCT and PET/CT are synergistic to play an important role in the solitary pulmonary nodules not to be definitely diagnosed by MSCT. It is favorable for us to combine the diagnosis of solitary pulmonary nodules by MSCT and PET/CT with the malignant probability and to improve the treatment project of solitary pulmonary nodules in clinical practice. As a result, management strategies for the imaging evaluation of the solitary pulmonary nodules will continue to be evolved. |
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