| [Objective]1. To study the change of tumor to non-tumor (T/N) value of18F-FDG imaging assess the early efficacy of chemotherapy and prognosis of advanced non-small-cell lung cancer (NSCLC). Analysis of the factors affecting patients survival.2. To explore the significance of the CT perfusion parameters, the greatest tumor diameter (GTD) and the gross tumor volume (GTV) before and after chemotherapy, these parameters changes predict1year survival time and progression-free survival (PFS) in patients with advanced NSCLC who had been treated with chemotherapy.[Methods]1.18F-FDG imaging studies of all patients with advanced NSCLC that was diagnosed and treated at the Shanghai Pulmonary Hospital between October2009and January2011were retrospectively reviewed. Of106patients,78patients were men and28were women, mean age57.87±10.36years, age range29to81years, median age58.50years.42patients were squamous cell carcinoma,64patients were adenocarcinoma.33patients were stage Ⅲ,73patients were stage IV. All patients are the first chemotherapy, received18F-FDG scan before one week of chemotherapy and after two cycle of chemotherapy. According to the T/N value change after chemotherapy,106patients were divided into decreased group (63patients) and increased group (43patients). Compared the T/N value, the T/N declining percentage change, and other clinical and pathological factors predict the outcomes and prognosis. All patients were followed up for1year. The Kaplan-Meier analysis was performed with gender, age, pathologic type, pathologic stage, the T/N percentage change in1year survival rate, and compare the survival curves of patients. The receiver operator characteristic curve (ROC curve) for1-year survival rate were calculated for T/N percentage change to identify prognostic optional cutoff. Cox proportional hazards model regression analysis were performed to find which were independent prognostic factors for advanced NSCLC after chemotherapy.2. Prospective selected46patients with advanced NSCLC at the Shanghai Pulmonary Hospital in March2011to May2011. All patients confirmed by pathological diagnosis (Lung puncture, Alveolar lavage fluid, Pleural effusion, Bronchoscopic biopsy). Which were analyzed in46patients with CT perfusion imaging before and6weeks after chemotherapy. The CT perfusion images of46patients were processed by specialized physicians before and after chemotherapy, then recorded data and save the images. Of46patients,40patients were men and6patients were women.The age range43to81years, mean age61.59±9.35years, median age61years. All patients were followed up for1year (clinical data and telephone). The perfusion parameters, GTD and GTV before and after chemotherapy were compared by paired t-testing. The survival curves for change in each parameters decreased group and increased group were calculated by using the Kaplan-Meier method. Log-rank tests were performed to assess the differences of survival rate. The predictive value of parameters in the Survival condition of patients within1year using the ROC curve.According to the coordinates of the curve to determine the optional cutoff in prediction of1year survival rate.At the same time,12of the46patients were18F-FDG metabolic imaging by the analysis, analyzed the relationship of perfusion parameters and T/N value ratio, as well as on the outcome of chemotherapy effect. Statistical analysis through SSPS17.0software in the computer, P<0.05was considered as significant difference (two-sided test).[Results]1.106patients with advanced NSCLC, The overall T/N value of before and after chemotherapy was6.99±5.20and6.39±4.52,respectively, before and after chemotherapy the T/N value of the overall difference was not statistically significant (t=1.521, P=0.131). After chemotherapy, The overall T/N value percentage change was8.23%±62.89%. Compared with different factors in subgroups of the T/N value, Before chemotherapy, The T/N value of the male group and female group was7.59±5.62and5.31±3.34, respectively, there was a significant difference (r=2.022,P=0.046); The T/N value of the age over65years group and low65years group was7.71±6.35and6.74±4.77, respectively, the difference was not statistically significant (t=0.830, P=0.408); The T/N value of squamous cell carcinoma group was higher than adenocarcinoma group, there was9.25±6.47and5.50±3.50, respectively, the difference was statistically significant (t=3.440, P=0.001); The T/N value of pathological stage Ⅲ and Ⅳ was7.88±6.45and6.61±4.55. respectively, the difference was not statistically significant (t=1.159, P=0.249). The T/N value of decreased group and elevated group was7.81±5.28and5.79±4.91. respectively, the difference was statistically significant (t=1.989, P=0.049). The T/N value in diffenent groups by the factors were compared after chemotherapy, the T/N value of male group and female group was6.60±4.71and5.82±3.96, respectively, the difference was not statistically significant (t=0.789, P=0.432); The T/N value of the age over65years group and low65years group was6.46±5.84and6.37±4.01, respectively, the difference was not statistically significant (t=0.080,P=0.936); The T/N value of squamous cell carcinoma group was higher than adenocarcinoma group, there was7.92±5.45and5.39±3.48. respectively, the difference was statistically significant (t=2.915,P=0.004); the T/N value of pathological stage Ⅲ and Ⅳ was6.84±5.69and6.25±3.89. respectively. the difference was not statistically significant (t=0.632, P=0.535):The T/N value of decreased group and elevated group was5.00±3.19and8.44±5.37. respectively, the difference was statistically significant (t=-4.130, P=0.000). Compared the T/N percentage change between the different factors groups, the male group and female group was4.78%±64.39%and17.83%±58.55%, respectively, the difference was not statistically significant (t=-0.941, P=0.349); The age over65years group and low65years group was-1.50%±66.81%and11.56%±61.58%, the difference was not statistically significant (t=-0.931, P=0.354); The T/N percentage change of Squamous cell carcinoma group and adenocarcinoma group was7.04%±69.22%and9.01%±58.93%, respectively, the difference was not statistically significant (t=-0.156, P=0.876); The T/N percentage change of pathological stage Ⅲ and Ⅳ was9.02%±65.68%and8.83%±61.95%. respectively, the difference was not statistically significant (t=0.015. P=0.988); The T/N percentage change of decreased group and elevated group after the chemotherapy was-31.18%±23.62%and65.97%±57.63%, respectively, the difference was statistically significant (t=-12.005, P=0.000). The T/N value and the T/N value percentage change in the difference groups (squamous cell carcinoma group and adenocarcinoma group, decreased group and elevated group) were statistically significant between before and after chemotherapy. There were no significant differences in the groups of age and pathological stage. The T/N value of gender group was statistically significant before chemotherapy. The T/N value and the T/N percentage change was no significant difference between gender group after chemotherapy. All patients were followed up for1year. In the period have26patients died. The overall1year survival rate was75.5%. The Kaplan-Meier method analysis was performed with gender, age, pathologic type, pathologic stage, the T/N percentage change in1-year survival rate, and compare the survival curves of patients. It showed only the T/N value of decreased group and increased group differences close to statistical significance during the1year survival curves (χ2=3.534, P=0.060). While the gender, age, pathological type and pathological stage were no statistically significant during the1year survival curves (χ2=0.098, P=0.754;χ2=0.372. P=0.542;χ2=1.688, P=0.194; χ2=2.454, P=0.117). Using ROC curve, the area under curve (AUC) was0.703,95%confidence interal (CI)(0.595-0.812), the optional cutoff in predictive1year survival was the T/N percentage declining10%,the sensitivity and specificity was76.9%and51.2%, respectively. By this cutoff value divided into two groups, the groups1year survival rate difference was statistically significant (χ2=6.502, P=0.011). Cox proportional hazards model regression analysis showed that the pathologic type, pathologic stage, the T/N percentage change were the independent prognostic factors for advanced NSCLC after chemotherapy (χ2=7.802, P=0.005;χ2=1.547, P=0.006;χ2=0.918, P=0.000).2. Before chemotherapy (the first CT perfusion imageing), the blood flow (BF) range7.60to150.63ml/100ml/min, the average (68.95±22.49) ml/100ml/min; The blood volume (BV) range3.89to13.58ml/100ml, the average (8.94±2.16) ml/100ml; The mean transit time (MTT) range5.13to16.24s,the average (9.86±2.24) s; The pemeability surface (PS) range4.29to29.94ml/100ml/min, the average(18.57±4.73) ml/100ml/min; The GTD range23.90to100.90mm, the average (57.13±18.80) mm; the GTV range0.62to579.55cm3, the average (63.92±99.69) cm3. After chemotherapy, the BF range7.50to219.22ml/100ml/min, the average (73.61±38.37) ml/100ml/min; The BV range1.15to17.07ml/100ml, the average (9.54±3.23) ml/100ml; The MTT range2.46to17.72s, the average (10.01±2.96) s; The PS range5.44to29.52ml/100ml/min, the average (18.03±5.40) ml/100ml/min; The GTD range22.00to87.30mm,the average (53.29±19.61) mm; The GTV range0.75to623.76cm3, the average (52.48±99.44) cm3. Each parameters showed no significant difference before and after chemotherapy (t=-1.119, P=0.269;t=-1.535, P=0.132; t=-0.350, P=0.728;t=0.843, P=0.404;t=1.919, P=0.061;t=1.906, P=0.063).46patients with advanced NSCLC,27patients died within1year,19patients more than1year. The overall1year survival rate was41.30%, median survival time was10.6months, median PFS was6.3months. Compared each parameters decreased groups and increased groups of1year survival rate after chemotherapy. After chemotherapy, the decreased groups of BF. BV, PS, GTD and GTV were23patients,17patients,21patients,29patients and32patients, respectively. The increased groups of these parameters were23patients,29patients.25patients,17patients and14patients, respectively. Log-rank tests were performed to assess the differences of survival rate were statistically significant (χ2=4.434, P=0.035;χ2=3.840. P=0.050;χ2=13.733, P=0.000;χ2=6.203, P=0.013; χ2=9.688, P=0.002). The decreased group of MTT was24patients,22patients increased after chemotherapy, the log-rank test showed1year survival rate was no significant difference (χ2=1.811, P=0.178). Compared each parameters decreased groups and increased groups in PFS after chemotherapy. After chemotherapy, the decreased group of PS was21patients, the median PFS was8.2months.95%CI:(7.61.8.79); elevated group was25patients, The median PFS was4.9months,95%CI:(3.77,6.04). The decreased group of GTV was32patients, the median PFS was8.0months,95%CI:(7.03,8.97); elevated group GTV was14patients,12patients progress in one year, the median PFS was4.0months,95%CI:(2.17,5.83). Log-rank tests showed the PFS of PS and GTV between decreased group and increased group difference were statistically significant (χ2=4.972, P=0.026; χ2=4.371, P=0.037). The decreased group of BF was23patients, the median PFS was8.3months.95%CI:(4.07,12.53); elevated group of BF was23patients, the median PFS was5.6months,95%CI:(3.41,7.79). The decreased group of BV was17patients, the median PFS was7.8months,95%CI:(5.51,10.09); elevated group of BV was29patients, the median PFS was5.6months,95%CI:(4.19.7.00). The decreased group of MTT was24patients, the median PFS was6.4months.95%CI:(3.76,9.04); elevated group of MTT was22patients, the median PFS was5.5months,95%CI:(2.93.8.07). The decreased group of GTD was29patients, the median PFS was7.8months,95%CI:(4.99,10.61); increased group of GTD was17patients, the median PFS was4.9months,95%CI:(2.88,6.92).Log-rank tests showed the PFS of these four parameters between decreased and increased group were not statistically significant (χ2=2.123, P=0.145;χ2=0.250, P=0.617; χ2=0.273, P=0.601;χ2=2.515, P=0.113). Analysis of the parameters of1-year survival rate, the ROC curve showed that the PS percentage change to predict1year survival has the greatest significant, AUC was0.848,95%CI:(0.736.0.960). The percentage change of GTD and GTV to predict1-year survival also have significant of the patients with advanced NSCLC, AUC were0.690and0.725,95%CI:(0.533,0.848) and95%CI:(0.573.0.877), respectively. The AUC between the three groups difference were no statistically significant. The AUC of percentage change of BF, BV and MTT were0.634.0.593,0.600, these ROC curves to predict patients1year survival rate were no significant. The ROC curve determine the best cutoff value of the1year survival rate was the PS percentage change declining5%, the sensitivity and specificity was81.5%and68.4%, respectively. By this cutoff value, patients were divided into two groups, the PS decreased more than5%was18patients, in which,5patients died within1year.28patients of the PS decreased less than5%. in which,22patients died within1year. Log-rank test showed two groups of1-year survival rates differences were statistically significant (χ2=11.488, P=0.001). Of the46patients,12patients had CT perfusion imaging and18F-FDG metabolic imaging, before chemotherapy, the BF range47.60to97.75ml/100ml/min, the average (72.44±16.05) ml/100ml/min; the BV range5.25to13.58ml/100mL, the average (9.34±2.30) ml/100ml; the MTT range6.09to13.33s, the average (9.77±2.33) s; the PS range12.43to29.94ml/100ml/min, the average (19.44±5.19) ml/100ml/min; the GTD range23.90to94.60mm, the average (23.90±94.20) mm; the GTV range1.90to162.71cm3, the average (41.86±55.50) cm3; T/N value range2.66to14.38, the average7,53±3.93. Due to the cases is too little, this portion of the data is only preliminary observation and analysis. Of12patients.8patients had the survival time less than1year, the BF range69.94to97.75ml/100ml/min, the BV over10ml/100mL, the PS over20ml/100ml/min, the T/N value over8.3of the8patients with the T/N value over10, these patients had a short period of progression, and the survival time are shorter than others.5of the8patients, the T/N value range5to8, the patients had progression more than6months, and the survival time more than the patients of the T/N value over10.4 patients had the survival time more than1year, the BF less than70ml/100ml/min, the BV less than10ml/100mL, the PS less than20ml/100ml/min, the T/N value range5to8. The prognosis is better in patients with lower BF, BV, PS and T/N value than the patients with higher, the perfusion parameter of BF. BV and PS values were higher in the patients with T/N value was also higher, the patients of the T/N value more than10with shorter period of progression and shorter survival time.The perfusion parameters of BF, BV, PS values with T/N value had positive correlation. The perfusion parameters and the T/N value can reflect the patients prognosis.[Conclusion]1. After two courses of chemotherapy. The T/N value percentage change for advanced NSCLC in evaluating curative effect and prognosis judgment to provide important reference value. The T/N value percentage change declining10%was the optional cutoff to predict1year survival rate. there was a significant difference in two groups of1year survival rate. Cox proportional hazards model regression showed that pathologic type, pathologic stage. T/N value percentage change were independent prognostic factors for the patients with advanced NSCLC after treated with chemotherapy. While age and gender are not independent prognostic factors for the patients with advanced NSCLC treated with chemotherapy.2. At six weeks after chemotherapy (the second CT perfusion imaging), the change of CT perfusion parameters, GTD and GTV for advanced NSCLC in predictive1year survival and progression-free survival (PFS) provide important reference value. The changes of BF, BV, PS, GTD and GTV can predict1year survival rate, in which, the changes of PS and GTV can predict PFS. There was no prediction value for1year survival rate and PFS using MTT. The ROC curves showed the percentage change of the PS, GTD and GTV to predict1year survival have significant in the patients with advanced NSCLC In which, the percentage change of PS to predict1year survival has the greatest significant, the AUC is the maximum. Using ROC curve, the optional cutoff of the PS percentage change in predictive1year survival rate was declining5%. By this cutoff value, patients were divided into two groups, there was significant difference of1year survival rate in two groups. Preliminary observation and analysis,the CT perfusion parameters of BF, BV, PS and T/N value may be have positive relationship, its may be have some associated with the prognosis. |
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