The Value Of ¹⁸F-FDG PET/CT Combined With Tumor Markers ProGRP And NSE In The Diagnosis And Differential Diagnosis Of Limited Stage Small Cell Lung Cancer

ObjectiveTo analyze the value of ¹⁸F-FDG PET/CT combined with tumor markers Pro GRP and NSE in the diagnosis and differential diagnosis of limited-stage small cell lung cancer（LS-SCLC）and to improve the accuracy of LS-SCLC diagnosis.MethodsPart I:From June 2017 to October 2021,patients with pathologically confirmed stage IA lung cancer and isolated benign nodules in the lung at our hospital were retrospectively analyzed.All patients underwent ¹⁸F-FDG PET/CT and lung cancer serum tumour marker tests including neuron-specific enolase（NSE）,gastrin-releasing peptide precursor（Pro GRP）,carcinoembryonic antigen（CEA）,squamous cell carcinoma-associated antigen（SCCA）and cytokeratin 19 fragment（CYFRA21-1）.Patients’gender,age,smoking history,lesion morphology,maximum diameter,density,CT signs,maximum standardized uptake value（SUVmax）of lesions and tumour marker levels were retrospectively collected.χ²test,Fisher exact test and Kruskal-Wallis rank sum test were used to compare the clinical,imaging and tumor marker data of different groups of patients according to the type of data.The independent predictors of stage IA SCLC were analyzed by logistic regression analysis.The value of different predictors in the diagnosis of stage IA SCLC was analyzed using the receiver operating characteristic（ROC）curve and the area under curve（AUC）was obtained.Part II:From June 2017 to October 2021,patients with clinically confirmed limited stage lung cancer excluding stage IA and intrapulmonary inflammatory lesions in our hospital were retrospectively analyzed.All patients underwent ¹⁸F-FDG PET/CT and lung cancer serum tumour markers（NSE,Pro GRP,CEA,SCCA and CYFRA21-1）tested within 2 weeks before and after the examination.Patients were analyzed for gender,age,smoking history,lesion location,shape,maximum diameter,density,CT signs,SUVmax of primary lesion and whether SUVmax of lymph nodes was higher than SUVmax of primary lesion.The clinical,imaging and tumor marker data were compared among different groups.χ²test and Kruskal-Wallis rank sum test were used to compare the differences in different groups according to the type of data.The independent predictors of SCLC were analyzed by logistic regression analysis.The value of different indicators in the diagnosis of SCLC was analyzed using ROC curves to obtain the AUC of this ROC curve.Finally,the differences in AUC between different diagnostic methods were compared using the Delong test.ResultsPart I:A total of 18 patients with stage IA SCLC,95 patients with NSCLC and 30patients with benign nodules were included in this study.The differences in SUVmax,lobulation sign,spiculation sign,calcification,pleural traction sign,Pro GRP,NSE and CEA among the three groups were statistically significant（all P<0.05）.Lobulation sign of SCLC was more than that of benign nodules（χ²=7.406,P=0.007）.The spiculation sign（χ²=10.008,P=0.002）and pleural traction sign（χ²=6.470,P=0.011）were less in the SCLC group than in the NSCLC group.The SUVmax and NSE levels of SCLC were higher than those of benign nodule group（H=51.822,40.533,P<0.001,P=0.001）.The Pro GRP levels of SCLC was higher than that of NSCLC group and benign nodule group（H=43.956,36.127,P=0.002,0.001）.When differentiated from NSCLC,the spiculation sign[ratio（OR）=0.043,95%CI:0.004-0.450,P=0.009]and Pro GRP>58.6μg/L（OR=1.083,95%CI:1.035-1.133,P<0.001）were independent predictors for SCLC.The AUC of the two predictors combination was 0.875,which was higher than that of the single predictor（Z=2.567,2.958;P=0.003,0.010）.When differentiated from benign nodules,SUVmax>4.4（OR=2.706,95%CI:1.099-6.662,P=0.030）,Pro GRP>45.4μg/L（OR=1.165,95%CI:1.009-1.344,P=0.038）,and NSE>8.8ng/L（OR=1.639,95%CI:1.016-2.645,P=0.043）were independent predictors for SCLC.The AUC of the three predictors combination was 0.985,which was higher than that of the single predictor（Z=2.281-3.213;P=0.001-0.022）.Part IIA total of 87 patients with LS-SCLC,137 patients with NSCLC and 48 patients with intrapulmonary inflammatory lesions were included in this study.The differences in age,shape of the lesion,maximum diameter of the lesion,spiculation sign,relationship of the long axis of the lesion to the bronchus,lymph node fusion,SUVmax of the primary lesion,SUVmax of the lymph node higher than SUVmax of the primary lesion,NSE,Pro GRP,CEA,SCCA and CYFRA21-1 among the three groups were statistically significant（all P<0.05）.Age（H=35.014,33.977）,maximum diameter of primary lesion（H=48.308,72.274）and SUVmax of primary lesion（H=93.555,107.404）were higher in the SCLC and NSCLC groups than in the inflammatory lesion group（all P<0.05）.Spiculation sign were more in the NSCLC group and inflammatory lesion group than SCLC group（χ²=27.056,13.127;P<0.001）.The incidence of lymph node fusion was higher in the SCLC group than in the NSCLCand inflammatory lesion groups（χ²=10.766,16.617;P=0.001,P<0.001）.SUVmax of the lymph node higher than SUVmax of the primary lesion was more in the SCLC and inflammatory lesion groups than in the NSCLC group（χ²=22.042,14.294;P<0.001）.Pro GRP levels（H=101.249,85.385;P<0.001）and NSE levels（H=113.307,93.540;P<0.001）were higher in the SCLC group than in the NSCLC and inflammatory lesion groups.The level of SCCA was higher in the NSCLC group than in the SCLC group（H=44.054;P<0.001）.The level of CYFRA21-1 was higher in the NSCLC group than in the SCLC group and the inflammatory lesion group（H=35.970,57.052;P<0.001）.When differentiated SCLC from NSCLC,spiculation sign（OR=0.282,95%CI:0.120-0.663,P=0.002）,NSE>23.5μg/L（OR=1.034,95%CI:1.001-1.068,P=0.043）,Pro GRP>111.8ng/L（OR=1.005,95%CI:1.003-1.007,P<0.001）,SCCA≤2.5μg/L（OR=0.829,95%CI:0.709-0.970,P=0.019）and CYFRA21-1≤7.4μg/L（OR=0.837,95%CI:0.717-0.977,P=0.024）were independent predictors for LS-SCLC.The AUC of five predictors combination was 0.912,which was higher than that of the single predictor（Z=2.508-8.270,all P<0.05）.When differentiated SCLC from inflammatory lesions,SUVmax>8.1（OR=2.890,95%CI:1.680-4.975,P=0.002）,NSE>19.4μg/L（OR=1.219,95%CI:1.017-1.461,P=0.032）and Pro GRP>72.5 ng/L（OR=1.042,95%CI:1.014-1.070,P=0.003）and lymph node fusion（OR=87.541,95%CI:3.807-2012.986,P=0.005）were independent predictors of LS-SCLC.The AUC of four predictors combination was 0.991,which was higher than that of the single predictor（Z=3.761-11.099,all P<0.05）.Conclusion¹⁸F-FDG PET/CT combined with the tumour marker Pro GRP and NSE has good predictive value in the diagnosis and differential diagnosis of stage IA SCLC and LS-SCLC.If evidence is sufficient,this method can be used for imaging pathology diagnosis and help guide clinicicans make better treatment decision,provide personalized treatment and improve patient prognosis.