Treatment Effects And Response Prediction To Chemotherapy For Advanced Non-small Cell Lung Cancer

BackgroundThird-generation cytotoxic agents plus platinum have extended survival of advanced non-small lung cancer(NSCLC). however, these gains in survival have been modest, with 25%～35% in overall response rate,4～6 month in median survival time and 8～10 month in time to progression,the treatment of advanced non-small lung cancer is remain unmanageable problem. It is the moment to think deeply how to give patient optimum therapeutic schedule: Is there a superior regimen based on histology? How to choose patient who will have good response before the chemotherapy? Therefore, it is most important to analyze the treatment effects and response prediction to chemotherapy for advanced NSCLC.ObjectiveInvestigate the efficacy of four cisplatin-based regimens for advanced NSCLC with different kinds of histology; analyze the relationship between 9^9mTc- methoxyisobutylisonitrile (^9mTc-MIBI) uptake rate and response of chemotherapy, to choose a feasible regimen for advanced NSCLC patients.MethodsIn a retrospective study, a total of 166 advanced NSCLC patients were studied, all of them were treated in Xinqiao hospital. they were assigned to regimens of TP,GP,NP,DP by different kinds of histology,squamous carcinoma is 94and adenocarcinoma is 72. Efficacies were evaluated every two cycles using response evaluation criteria in solid tumors by World Health Organization. Toxicities were assessed at the end of every cycle; Toxicities were graded from 0 toⅣ°. Before and after chemotherapy, all patients were given computerized tomography image. Survival time were registered monthly, Survival was measured from the time of chemotherapy to date of death or date of last follow-up investigation by outpatient service, readmission and telephone. Characteristics, response and toxicities were valued by Chi-square test, survival time and survival rate at 1 year were evaluated based on Kaplan-Meier survival analyses and log-rank test.^9mTc-MIBI were performed in 19 advanced NSCLC patients within a week of pre-chemotherapy , early image and delay image were took in 20 min and 150 min,respectively.Then, they were chose to be given regimens of TP,GP,NP,DP. ^9mTc-MIBI SPECT qualitative analysis was diagnosed by more than two nuclear medicine technologists, radioactive concentration is determination criteria. Quantitative analysis based on 9^9mTc-MIBI uptake by tumor. Using a ratio of the average counts in the lesion to those in the contra lateral normal region on the early (T/Ne) and delayed (T/Nd) SPECT images and retention index (RI) defined as the percentage of change in ^9mTc-MIBI uptake, was calculated using [(T/Nd- T/Ne)/ T/Ne]×100%.the relationship between T/Ne,T/Nd,RI% and response of chemotherapy, clinical factor and response of chemotherapy were assessed by the Independent-Samples T Test for statistical analysis. Probability values < 0.05 were considered significant.Results1. Treatment effects of four cisplatin-based regimens for advanced NSCLC (1) Overall response rate (ORR) were 34.9%. squamous carcinoma and adenocarcinoma's ORR were 38.3% and 30.6% ,respectively.In TP,GP,NP,DP regimen's groups, squamous carcinoma's ORR were 41.7%,44.0%,34.8%,31.8%,median survival time (MST) were 12.1,12.3,11.7,11.8 months,Time to progression (TTP) were 4.4,4.5,3.1,4.4 months,1-year survival rate were 45.0%,44.0%,34.9%,36.4% respectively;adenocarcinoma's ORR were 27.8%,25.0%,40.0%,28.6%,MST were 11.2,11.1,11.5,10.4 months; TTP were 3.7,3.2,4.0,4.7 months,1-year survival rate were 33.3%,30.0%,35.0%,35.7% respectively.ORR,MST,TTP,1-year survival rate haven't significant differences in two groups(P>0.05).Different clinical stage and different clinical factor couldn't influence treatment effects. (P>0.05). (2)The major adverse reactions were myelo-suppression,nausea,vomiting,phlebitis,alopecia. There were highest incidence of thrombocytopenia (51.1%)in GP compared to other groups, especiallyⅢ°,Ⅳ°thrombocytopenia(24.4%) in GP(P<0.05). The incidence of nausea,vomiting in NP (37.2%) is significant higher than others(P<0.05). There were more phlebitis in NP (P<0.05).2. The relationship between ^9mTc-MIBI uptake rate and response of chemotherapy (1) Within 19 advanced NSCLC patients who had been given ^9mTc-MIBI chest SPECT, positive image was 18, only 1 was negative, accuracy was 94.7%.The good-response to chemotherapy was 8, unresponse to chemotherapy was 11, the overall response was 42.1%. T/Ne mean was 2.05±0.42,T/Nd mean was 1.95±0.40,RI% mean was -4.80±3.81;all positive images'T/Ne greater than 1.30(.2)T/Ne for good-response was2.47±0.23,all T/Ne for good-response were more than 2.0,T/Ne for poor-response was 1.72±0.10,all T/Ne for poor-response were less than 2.0;T/Nd for good-response was2.35±0.19 , T/Nd for poor-response was 1.63±0.12,T/Ne and T/Nd for good-response is significant higher than the ones for poor-response(P < 0.05);RI% for good-response was-4.45±2.24,RI% for poor-response was -5.07±4.83,there wasn't difference between two group in RI%(P > 0.05);(3)T/Ne,T/Nd,RI% wasn't difference in clinical stage,histology gender(P > 0.05).(4) clinical stage,histology and gender couldn't affect ^9mTc-MIBI chest SPECT accuracy of prediction to chemotherapy(P > 0.05).Conclusion1. Four cisplatin-based regimens(TP,GP,NP,DP) is benefit to NSCLC patient, TP,GP is more efficacy regimens for squamous carcinoma of lung, NP is more efficacy regimens for adenocarcinoma of lung, DP is efficacy regimens for two kinds of histology. The incidences of adverse reactions were different, so the choice of chemotherapy by clinicians should be based on individual conditions of patients.2. 9^9mTc-MIBI chest imaging can diagnose non-small lung cancer,when early image and delay image were took in 20 min and 150 min,respectively,T/Ne>1.30 is a high probability of malignancy. However, when it is negative image, further examination is necessary.3. 9^9mTc-MIBI chest imaging can predict the chemo-sensitivity of NSCLC, when early image and delay image were took in 20 min and 150 min,respectively,T/Ne=2.0 is critical point for predict the chemo-sensitivity, It maybe feasible to choose T/Nd as chemo-sensitivity prediction of advanced NSCLC,.The role of RI remain to be observed. T/Ne,T/Nd,RI% wasn't difference in clinical stage,histology gender. Clinical stage,histology and gender couldn't affect ^9mTc-MIBI chest SPECT accuracy of prediction to chemotherapy.