Evaluation Of Lung Metastasis And Prognosis Of Osteosarcoma Based On Circulating Tumor Cells

Objective: To evaluate lung metastasis and prognosis of osteosarcoma by detecting the number and the phenotype of circulating tumor cells(CTC)in peripheral blood.Materials and Methods: Data of osteosarcoma patients,who underwent CTC testing in the Department of Oncologic Orthopedics,from February 2015 to April 2016,were collected.The lung metastasis-free survival(LMFS)and the overall survival(OS)were obtained from the follow-up visit.SPSS 21.0 software was used for statistical analysis.Med Calc software was used to determine the optimal cut-off value of CTC and to group,so as to drawn the interactive scatter plots.Mann-Whitney U test and Chi Square test were used to compare the differences of the groups.Kaplan-Meier curves were used to compare the effects of different factors on survival.Univariate and multivariate regression analyses were performed,by using Cox proportional hazards model,to analyze the correlation between the number and phenotype of CTC and the lung metastasis and prognosis of osteosarcoma.Results:(1)In our study,the median follow-up time was 59.0 months,the median LMFS was 25.4 months,the median OS was 59.0 months,and the 5-year survival rate was 58.1%.The CTC detection rate of osteosarcoma was 93.0%(40/43),while was100%(23/23 or 18/18)in lung metastasis or death patients.The detected CTC,was divided into three types: epithelial circulating tumor cell(E-CTC),mesenchymal circulating tumor cell(M-CTC)and hybrid circulating tumor cell(H-CTC).Moreover the total number of circulating tumor cell(T-CTC)was calculated.(2)When the data was analyzed,same with E-CTC(P=0.029),H-CTC(P=0.001)and M-CTC(P=0.009),the number of T-CTC in the group with lung metastasis was higher than that in the group without lung metastasis(P=0.001).The optimal cut-off values of CTC for lung metastasis were obtained and grouped by Med Calc software(T-CTC: 4/7.5ml,E-CTC:0/7.5ml,H-CTC: 4/7.5ml)and M-CTC: 2/7.5ml).Kaplan-Meier survival curves showed that,same with the E-CTC group(P=0.033),H-CTC group(P=0.004)and M-CTC group(P=0.006),the median LMFS in the low-level T-CTC group(P=0.001)was higher than that in the high-level group.Cox univariate analysis suggested that lung metastasis of osteosarcoma might be associated with Enneking stage(P<0.001),tumor size(P=0.003),T-CTC(P=0.009),E-CTC(P=0.044),H-CTC(P=0.008)and M-CTC(P=0.009).Multivariate analysis suggested that T-CTC was an independent risk factor for lung metastasis in patients with osteosarcoma(HR=12.242,95%CI:1.091-137.321,P=0.042).(3)When the data was analyzed,same with the E-CTC(P=0.036),H-CTC(P=0.010)or M-CTC(P=0.043),the number of T-CTC in the death group was higher than that in the group with survival group(P=0.001).The optimal cut-off values of CTC for death differentiation,according to which the patients were grouped as follow: T-CTC: 5/7.5ml,E-CTC: 0/7.5ml,H-CTC: 3/7.5ml,M-CTC: 2/7.5ml.Kaplan-Meier survival curves showed that the median OS,same with the group of E-CTC(P=0.018),H-CTC(P=0.008)and M-CTC(P=0.012),in the low level T-CTC group(P=0.007)was longer than that in the high level group.Cox univariate analysis suggested that the prognosis of osteosarcoma may be related to Enneking stage(P=0.001),tumor size(P=0.033),T-CTC(P=0.028),E-CTC(P=0.033),H-CTC(P=0.016)and M-CTC(P=0.017).COX multivariate analysis did not find the relationship between total survival of osteosarcoma and age,sex,Enneking stage,tumor size,or all type of the CTCs(all P values> 0.05).Conclusions: The number of CTC detected in patients with lung metastasis or death was higher than that in patients without lung metastasis or survival respectively,higher CTC levels are associated with lower LMFS and OS,T-CTC is an influential factor for lung metastasis in patients with osteosarcoma.However,no association was found between overall survival of osteosarcoma and CTC.