| Part one Early response to EGFR-TKIs therapy or chemotherapy inpatients with lung cancer assessed by 18F-FDG PET/CTPurpose:This study aimed to explore the value of 18F-FDG PET/CT for monitoring early response of epidermal growth factor receptor tyrosine kinase inhibitors?EGFR-TKIs?therapy or chemotherapy in patients with advanced-stage lung cancer.Methods:A total of 40 patients with diagnosed lung adenocarcinoma cancer treated in The Fourth Hospital of Hebei medical university from May2012 to December 2016 were evaluated in this study.All patients underwent18F-FDG PET/CT before and after therapy.Thirty-one patients were treated with EGFR-TKIs,and the other 9 cases accept chemotherapy.Baseline SUVmax,baseline MTV,baseline TLG,post therapy SUVmax and the change rate of SUVmax in the target lesion of lung were measured and calculated.EORTC?European Organization for Research and Treatment of Cancer?was used as criteria to evaluate the response to therapy.The difference between EORTC and RECIST?Response Evaluation Criteria in Solid Tumors?1.1criteria on the evaluation of therapy response was compared.SPSS 13.0software was used to analyze the correlation between the change rate of SUVmax,baseline SUVmax,baseline MTV,baseline TLG,post therapy SUVmax and PFS?Progression-free survival?and OS?Overall survival?by Pearson.The survival rate between response and nonresponse groups were plotted by Kaplan-Meier,and the difference of survival curves between two groups were tested by Log-rank test.The difference between EORTC and RECIST1.1 was analyzed by Wilconxon Signed-Rank Test.Clinical relevant factors were assessed by Cox regression analysis of proportional hazards.P<0.05 was considered statistically significant.Results:According to EORTC criteria,26 cases were responders?1 case was CMR,25 cases were PMR?,14 cases were nonresponders?9 cases were SMD,5 cases were PMD?.SUVmax of target lesion in the response group before and after treatment were 8.37±3.65 and 3.87±1.90,respectively.The difference between the two groups was statistically significant?t=5.582,P=0.000?.In the nonresponse group,SUVmax of lung target lesion before and after therapy were 5.48±2.70 and 6.61±3.62,respectively.There was no significant difference between the two groups?t=-0.936,P=0.358?.The change rate of SUVmax in the response and nonresponse group were51.82%±18.88 and-28.51%±58.67,respectively.The difference between the two groups was statistically significant?t=4.986,P=0.000?.The median PFS of response and nonresponse group were 9 months?95%CI:6.19-11.81months?and 5 months?95%CI:0-12.33 months?.The difference between the two groups was statistically significant?P=0.039?.There was a moderate positive correlation between the change rate of SUVmax and PFS?r=0.423,P=0.007?.There was a weak positive correlation between the change rate of SUVmax and OS?r=0.221,P=0.171?.There was no significant correlation between baseline SUVmax and PFS or OS?r=0.098 and-0.135,P=0.549 and0.408,respectively?.There was a weak negative correlation between post therapy SUVmax and PFS or OS?r=-0.350 and-0.299,P=0.027 and 0.061,respectively?.There was a weak negative correlation between baseline MTV and PFS or OS?r=-0.227 and-0.331,P=0.192 and 0.048,respectively?.There was a weak negative correlation between baseline TLG and PFS or OS?r=-0.222 and-0.365,P=0.225 and 0.029,respectively?.According to RECIST 1.1,there was no CR patient,13 PR patients,23 SD patients and 4PD patients.13 patients were responders and 27 were nonresponders.The difference between RECIST 1.1 and EORTC was statistically significant?Z=-7.824,P=0.000?,Kappa value was 0.231?<0.4?.Cox regression analysis of proportional hazards showed the change rate of SUVmax was the independent predictor of PFS?HR=2.60,P=0.033?.The age,gender,treatment methods,baseline SUVmax,baseline MTV and baseline TLG were not the independent predictor of PFS?P=0.183,0.636,0.469,0.372,0.507 and 0.636,respectively?.Part two 99mTc-3PRGD2 SPECT/CT imaging for monitoring earlyresponse of EGFR-TKIs therapy or chemotherapy in patients with advanced-stage lung adenocarcinomaPurpose:This study was aimed to assess the efficacy of 99mTc-3PRGD2SPECT/CT for evaluating of both early treatment response and prognosis to EGFR-TKIs therapy or chemotherapy in patients with advanced-stage lung adenocarcinoma.Methods:From May 2012 to December 2016,30 patients with lung adenocarcinoma received EGFR-TKIs treatment or chemotherapy in The Fourth Hospital of Hebei Medical University were prospectively studied.21patients were treated with EGFR-TKIs and 9 patients were treated with chemotherapy.All patients were pathologically diagnosed with lung adenocarcinoma without any treatment before this study.99mTc-3PRGD2SPECT/CT and 18F-FDG PET/CT were performed before and post therapy.The tumor to non-tumor?T/NT?ratio,SUVmax and percentage change in T/NT ratio and SUVmax were assessed for the treatment response.EORTC was used as criteria in distinguishing responders and nonresponders.To identify an optimal cut-off value of identifying responders using percentage change in T/NT ratio on 99mTc-3PRGD2 SPECT/CT image,receiver operator characteristic?ROC?analysis was performed.According to the optimal cut-off value,the patients were regrouped into responders?S1?and nonresponders?S2?.Progression free survival?PFS?and overall survival?OS?between S1and S2 was compared.Statistical analyses were performed using SPSS 13.0software.P values of less than 0.05 were considered significant.Results:After treatment,1 patients had CMR?complete metabolic response?,19 patients PMR?partial metabolic response?,and 7 patients SMD?stable metabolic disease?,while 3 patients PMD?progressive metabolic disease?.In responder group?CMR+PMR?,the mean T/NT ratio of lung lesions on SPECT/CT image before and after treatment were 5.95±2.75 and4.49±1.88,respectively.There was a significant difference?t=3.501,P=0.002?.while in nonresponder group?SMD+PMD?,the mean T/NT ratio before and after treatment were 7.64±4.09 and 8.06±3.98,respectively.There was no significant difference?t=-0.932,P=0.376?.The mean changes of T/NT ratios on SPECT/CT in responders?CMR+PMR?and nonresponders were 20.2%and-8.7%,respectively.There was a significant difference between responders and nonresponders?t=3.473,P=0.002?.For ROC analysis,using a cut-off value of 8.6%decrease in T/NT ratio on SPECT/CT images,the sensitivity and specificity in identifying responders were 85.0%and 90.0%,respectively.The median PFS for patients with responders and nonresponders(on 99mTc-3PRGD2 SPECT/CT)were 12.5 months?95%CI:8.34-16.66months?and 6 months?95%CI:0.91-11.1 months?,respectively?P=0.001?.The median OS for patients with responders and nonresponders(on99mTc-3PRGD2 SPECT/CT)were 36 months?95%CI:15.61-56.39 months?and 22 months?95%CI:18.61-25.40 months?,respectively?P=0.159?.Part three Comparison of 99mTc-3PRGD2 SPECT/CT and 18F-FDGPET/CT for assessing early response and prognosis to targe ted therapy or chemotherapy in patients with lung adenocarcinomaPurpose:The aim of this study was to compare the application of99mTc-3PRGD2 SPECT/CT and 18F-FDG PET/CT for evaluation of early response and prognosis in patients with advanced lung adenocarcinoma treated with EGFR-TKIs or chemotherapy.Method:Thirty patients with advanced-stage lung adenocarcinoa and received EGFR-TKIs therapy or chemotherapy were included in this prospective study.Of 30 patients,21 were treated with EGFR-TKIs,9 were treated with pemetrexed disodium combined with cisplatinum complexes.99mTc-3PRGD2 SPECT/CT and 18F-FDG PET/CT were performed for all patients at baseline and after 42.14±4.63 days of EGFR-TKIs therapy or two cycles?42.0 days?of chemotherapy.The tumor to non-tumor?T/NT?ratio and SUVmax of target lesions in lung were measured on 99mTc-3PRGD2SPECT/CT and 18F-FDG PET/CT images separately.Data were analyzed with Student's t test and Pearson correlation.Results:After treatment,23 patients had 99mTc-3PRGD2 uptake decreased,and 7 patients had 99mTc-3PRGD2 uptake increased.There were 24patients with the uptake of 18F-FDG decreased,1 patient with no change and 5patients increased.All target lesions in lung had significant 99mTc-3PRGD2and 18F-FDG uptake at baseline.Before treatment,SUVmax and T/NT ratio were 7.17±3.65 and 6.51±3.29 for all patients?r=0.104,P=0.586?.After treatment,SUVmax and T/NT ratio were 4.65±2.69 and 5.68±3.18?r=0.449,P=0.013?.The percentage change of SUVmax and T/NT were 29.49%and10.56%,respectively.There was positive correlation in percentage change between T/NT ratio and SUVmax after treatment?r=0.660,P=0.000?.There was also positive correlation between the percentage of T/NT ratio and PFS?r=0.521,P=0.003?.Between the percentage of SUVmax and PFS,there also had positive correlation?r=0.574,P=0.001?.There were no correlation between the percentage of T/NT ratio,SUVmax and OS?r=0.047 and 0.118,P=0.806 and 0.536,respectively?.The average percentage change of SUVmax in patients with PFS over 1 year and less than 1 year were 55.27%and16.60%,respectively.The difference was statistically significant?t=3.080,P=0.005?.The average percentage change of T/NT in patients with PFS over 1year and less than 1 year were 25.30%and 3.20%,respectively.The difference was statistically significant?t=2.446,P=0.021?.Conclusions:1.The change rate of SUVmax after treatment of lung adenocarcinoma can be used for early and accurate evaluation of response and prognosis.The change rate of SUVmax is an independent predictor of PFS.Baseline MTV and TLG can be used for prognosis evaluation before therapy.18F-FDG PET/CT is superior to CT in the early evaluation of response to therapy.2.99mTc-3PRGD2 SPECT/CT imaging can image the change of integrin receptor?v?3 in lung adenocarcinoma after EGFR-TKIs or chemotherapy,which can be used for early evaluation of response and prognosis after treatment.3.Compared with 18F-FDG PET/CT,99mTc-3PRGD2 SPECT/CT also has the ability to evaluate early response and prognosis to EGFR-TKIs or chemotherapy in patients with lung adenocarcinoma. |
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