TNM Staging Of Peripheral Non-Small Cell Lung Cancer Correlated To The Enhanced Index Of The 16-Slice Spiral CT Perfusion Imaging And MVD Of Tumor

ObjectiveTo evaluate quantificationally tumor angiogenesis of peripheral non-small cell lung cancer (NSCLC)by the 16-slice spiral CT(16-SCT) perfusion.To investigate the correlationsB and clinical application of TNM staging and the enhanced index of the 16-SCT perfusion in first pass phase of NSCLC as well as tumor angiogenesis.Materials and methods1.Between March 2008 and the middle September 2009,32 patients(20 men,12 women;age range,27~72 years;mean age,55.69 years;size range,1.8~6.5cm;mean size of the lesions,4.29cm)with definite masses who were detected by Chest X-ray or plain CT Scanning were chosen to perform Multislice Computerized Tomography(MSCT).All the patients had no anticancer therapy before the perfusion scanning,and had radical resection of lung cacer in 1~2weeks after that.All lesions were confirmed to be NSCLC(squamous cancer 10 cases,adenocarcinama 19 cases with alveolar cell carcinoma 1 case,adensquanmous carcinoma 3cases) by pathological examination after surgical resection.The clinical document(including operating record,histological report and situations of lymphatic involvement) is integrated.All surgical lymph nodes had pathological examination to observe whether there is any cancer invation,strucral violation,envelope invation and metastasis in these nodes.2. All patients underwent unenhanced CT scanning firstly with SIMENSE Sensation 16 CT scanner. Then four or eight adjacent sections locating the center of the lesion were chosen to be the target sections and CT perfusion scanning in first pass phase(FPP) was performed by the"Toggling-Table"technology. The section thickness was 3mm for lesions less than 3cm in diameter and 6mm for lesions largerer than 3cm.For perfusion scanning, following parameters: 120 KV, 80mA, cine full, 0.5second scan time per circle, non-ionic agent (350 mg I/ml) 40 ml, infusion rate of 4.0ml /sec, scanning started at 6 seconds after the beginning of injection and acquisition time of 30 seconds were used.3. All perfusion images were transferred into Volume Wizard workstation. The time-density curves (TDC) were creased from regions of interest drawn over the tumor and aorta by the DynEva software in the workstation, and calculate CT perfusion(CTP) enhance index of the region of interest(ROI): the peak height (PH) of mass, the ratio of the peak height of mass to the peak height of aorta (M/A), then the perfusion value(PV) was calculated using the maximum-slope method.4. Pathologic types of specimens were determined by hematoxylin and eosin (HE) staining. The expression of CD34 in 32 cases were detected by LSAB immunohistochemistry staining, then the Microvessel Density (MVD) counting by Weidner method was performed.5.Refer to the seventh version TNM staging of lung cancer released by the International Association for the Study of Lung Cancer(IASLC) latestly in 2009 to stage lung cancer.6. Statistical Analysis: The statistical analysises were performed with spss13.0 software.Kappa value was applicated to analyze the consistency between MSCT staging and pathological staging of lung cancer. Two-sample t test was used (if necessary, with correction for unequal variance with the two-sample t'test ) to test the difference of CTP enhancement index and MVD between differernt T stagings,lymph situations and TNM stagings. A Pearson correlation coefficient test was used to compare the CTP enhancement index and MVD. The receiver operating characteristic curve(ROC) analysis was used to estimate the efficiency of CTP enhancement index (PV)as well as histological parameter (MVD) to predict the TNM staging of lung cancer ,and to select the cutoff points for dichotomization of PV and MVD for the criterion as the greatest overall accuracy.Results1.Peripheral NSCLC of 32 cases were compared between MSCT and pathological TNM staging with 22 cases of correctness and 10 cases of misdiagnosis.The sensitivity ofⅠ,ⅡandⅢ~Ⅳstaged by MSCT was 75%,66.67%,64% respectively, the specificity of which was 91.67%,82.61%,70.89% respectively,the accuracy was 87.50%,78.13%,65.63% respectively,the positive predictive value was 75%,60%,60.29% respectively,and the negative predictive value was 91.67%,83.36%,66.67% respectively.The coincidence between MSCT and pathological TNM staging was 68.75%(22 cases in 32;Kappa value was 0.566,and p value was 0.000),so we could consider that these two have coincidence.2. The CTP enhance index (PH,M/A,PV) of lung cancer correlated positively with the MVD ,respectively , and he highest correlation coefficient was between the PV and MVD(r=0.703, p <0.01) .3.32 patients of peripheral NSCLC were divided into two groups using 3cm in diameter as the boundary of T1 and T2 stage(the number of≤3cm and >3 group was 6 and 26 respectively;and mean diameter of the two groups was 2.52cm and 4.67cm respectively).No significant differences of CTP enhance index(PH,M/A,PV) were found in the two groups(p>0.05),and neither did MVD(p>0.05).Use pleural invasion or not as the boundary of T1 and T2 stage(11 cases with visceral and parietal invasion or pleural effusion,and 21 cases without pleural invasion).Tumors with pleural invsion had higher value of PV and MVD than those without pleural invasion(p<0.05).No significant differences of PH and M/A were found in the two goups(p>0.05).4.32 patients of lung cancer were divided into two groups using lymphatic involvement as the boundary of N0 and N1~2 stage(16 cases with lymphatic involvement and 16 cases without lymphatic involvement).Tumors with lymphatic involvement had higher value of CTP enhance index(PH,M/A,PV) and MVD than those without lymphatic involvement(p<0.05).5. 32 patients of lung cancer were divided into two groups(17 cases inⅠ~Ⅱand 15 cases inⅢ~Ⅳ).Tumors inⅢ~Ⅳhad higher value of CTP enhance index(PH,M/A,PV) and MVD than those inⅠ~Ⅱ(p<0.05).6.MVD and PV were valuable in estimating TNM staging of lung cancer when using MVD and PV to predict TNM staging of lung cancer(their AZ was 0.812 and 0.729 respectively) ,and no significant difference was found in them using u test(p>0.05).ROC curve was used to check out the optimal thershold of MVD and PV in predicting TNM staging of lung cancer.If MVD>71.5 unit/mm2 was taken as a threshold to predict TNM staging of lung cancer,the sensitivity,specificity and coincidence was 86.7%,76.5% and 81.13% respectively;If PV>1.16ml/min/ml was taken as a threshold to predict TNM staging of lung cancer,the sensitivity,specificity and coincidence was 73.3%,52.9% and 62.5%.ConclusionThe MSCT perfusion enhance index could reflect the characteristics of microvascular density in NSCLC. The CTP enhance index had good correlation with TNM staging and MVD of lung cancer. And it provides a new method in vivo evaluating TNM staging and of prognosis of lung cancer.