Correlation Analysis Of TTF-1 With Efficacy,Side Effects Of First-line Chemotherapy And Prognosis In Patients With Extensive-stage Small Cell Lung Cancer

ObjectiveThyroid transcription factor-1(TTF-1)is one of the commonly used diagnostic markers of lung cancer.The carcinogenic mechanism and effect on prognostic value of TTF-1 have been studied extensively and deeply in lung adenocarcinoma.However,the clinical significance of TTF-1 expression in small cell lung cancer(SCLC)is seldom studied and the results are different.In this study,the expression of TTF-1 in newly diagnosed extensive-stage disease SCLC(ED-SCLC)patients was observed to explore the relationship between the expression of TTF-1 and ED-SCLC(clinicopathological characteristics,response of first-line platinum-based chemotherapy,long-term survival and common side effects of chemotherapy)and further to estimate the predictive value of TTF-1 on ED-SCLC patients.MethodA total of 239 patients with ED-SCLC who were pathologically diagnosed and treated at the Affiliated Hospital of Qingdao University between January 2012 and January 2019 were randomly selected.The electronic medical record system was used to query and collect the relevant clinicopathological data of the patients,including TTF-1 expression,Ki-67 index,imaging data,age,gender,smoking history,and Karnofsky Performance Status(KPS)score,metastatic site at initial diagnosis and during first-line chemotherapy,first-line chemotherapy regimen,blood routine Index,liver function and kidney function at initial diagnosis and during first-line chemotherapy.Overall survival(OS)of patients were also followed up.The Chi-square test was used to evaluate the association between TTF-1expression status and clinicopathological characteristics of the patients,disease control rate(DCR)and objective response rate(ORR)of first-line platinum-based chemotherapy.Univariate and multivariate Logistic regression models were used to screen out the related factors on ORR of first-line platinum-containing chemotherapy in patients with ED-SCLC.Kaplan-Meier method was used to fit the OS survival curves of patients in TTF-1(+)group and TTF-1(-)group,and Log-rank method survival analysis was used to preliminarily screen the influencing factors of OS in EDSCLC patients,and the statistically significant variables in univariate analysis were incorporated into the multivariate COX proportional hazard regression model to determine the independent prognostic factors of OS.Chi-square test was used to evaluate the univariate effects of TTF-1 expression on hematological toxicity and hepatotoxicity of firstline platinum-based chemotherapy,and multivariate Logistic regression model was established to evaluate the multivariate effects by adjusting related confounding factors.P< 0.05 indicated that the difference was statistically significant.Result1.A total of 239 newly diagnosed patients with extensive-stage SCLC were included in this study.TTF-1 expression in 191(79.9%)patients were positive and 48(20.1%)were negative.The expression of TTF-1 was not significantly correlated with sex,age,smoking history,Ki-67 index,imaging location classification of primary primary tumor,KPS score,bone metastasis at initial diagnosis and first-line chemotherapy,but correlated with liver metastasis(χ ~2= 25.056,P < 0.001)and brain metastasis(χ ~2= 5.818,P < 0.016).The patients with negative TTF-1 expression had higher risk of liver metastasis(47.9% vs 14.7%,P <0.001)and brain metastasis(39.6% vs 22.5%,P=0.016)at initial diagnosis or during firstline chemotherapy.TTF-1 expression status was not significantly associated with gender,age,smoking history,Ki-67 index,radiographic location of primary lesion,KPS score,presence of bone metastases at initial diagnosis or during first-line chemotherapy(P>0.05),but was associated with presence of liver metastases(χ~2=25.056,P<0.001)and brain metastases(χ~2 = 5.818,P = 0.016)at initial diagnosis stage or during first-line chemotherapy.2.Univariate analysis showed that the expression status of TTF-1 was correlate d with DCR(positive:94.8% vs negative:81.3%,P=0.002)and ORR(positive:64.4% v s negative:39.6%,P=0.002)of first-line platinum-containing chemotherapy.Logistic re gression multivariate analysis showed that ED-SCLC patients with TTF-1 positivity exhibited higher ORR to first-line chemotherapy compared to TTF-1 negative patie nts.TTF-1 expression status was an independent predictor of ORR to first-line pla tinum containing chemotherapy in ED-SCLC patients(HR=2.865,95%CI:1.470-5.582,P=0.002).3.The median OS of TTF-1 positive group was 12.4 months,while that of TTF-1negative group was 9.9months,with significant difference(P=0.002).Multivariate survival analysis revealed that TTF-1 expression status was an independent prognostic factor for OS in ED-SCLC patients(HR=0.640,95%CI:0.456-0.898,P=0.010),and negative TTF-1 expression predicted worse OS.4.The expression status of TTF-1 is related to the hematological toxicity of first-line platinum-containing chemotherapy.Patients with positive TTF-1 expression had a higher probability of developing grade Ⅲ-Ⅳ neutropenia during the course of first-line chemotherapy compared with those with negative TTF-1 expression(63.9% vs 43.8%,HR=2.118,95%CI:1.103-4.071,P=0.024).There was no correlation between the expression of TTF-1 and the occurrence of high-grade liver toxicity in first-line chemotherapy(P>0.05).ConclusionThe expression of TTF-1 is a potential marker of short-term efficacy,long-term prognosis and hematological side effects of first-line platinum-containing chemotherapy in patients with ED-SCLC.The positive expression of TTF-1 predicted higher chemotherapy ORR,better OS and higher incidence of neutropenia of grade Ⅲ-Ⅳ.