The Prognostic Value Of Tumor Volume And Tumor Volume Reduction Rate During The Course Of Treatment In Cervical Cancer Patients Treated With Concurrent Chemoradiotherapy

Objective: To investigate the prognostic value of changes in primary tumor size and volume parameters by imaging(pre-radiotherapy tumor size and volume: pre-RT TS and pre-RT TV,mid-radiotherapy tumor size and volume: mid-RT TS and mid-RT TV,tumor volume reduction rate: TVRR),before and after external beam radiotherapy(EBRT)in patients with local advanced cervical cancer.Methods: From 2009 to 2016,310 patients with cervical squamous cell carcinoma were treated in Sichuan Cancer Hospital and received radical concurrent radiotherapy and chemotherapy were retrospectively analyzed.The clinical characteristics including age,FIGO stage,treatment and magnetic resonance imaging(MRI)data for all patients,before and after EBRT,were available.According to the Common Terminology Criteria for Adverse Events(CTCAE version 4.03,2010),the levels of toxicity and side effects related to treatment were calculated.The cut-off points of the continuous tumor parameters with prognositic value were determined by using the ROC and Youden indices.The predictive ability of each tumor parameter to OS,PFS and LFFS was compared with the area under the curve(AUC).The patients were grouped according to the best cut-off values of different tumor parameters.The survival curves for OS,PFS and LFFS were derived by the Kaplan–Meier method.The relative risk of death was estimated as hazard ratio(HR)using Cox regression.Multivariate survival analyses were adjusted for age,FIGO stage,TV,TS and TVRR separately.Covariates were stratified for in the analysis if they did not meet the proportional hazards assumption.Results: The 5-year OS,PFS and LFFS rates of all enrolled patients were 84.3%,79.1% and 88.6%,respectively.The median follow-up time was 50 months(range,5–111 months).In univariate analysis,the FIGO stage ? patients compared to stage ? and ? patients(P = 0.004),the pre-RT TS >5.5 cm group compared to the ?5.5 cm group(P = 0.006),the pre-RT TV >40.22 cm~3 group compared to the ?40.22 cm~3 group(P = 0.029),and the mid-RT TS >1.9 cm group compared to the ?1.9 cm group(P = 0.019),the mid-RT TV >11.06 cm~3 group compared to the ?11.06 cm~3 group(P < 0.0001),and the TVRR ?86.7% group compared to the >86.7% group(P < 0.0001),all showed worse OS.As for PFS,the FIGO stage ? patients compared to stage ? and ? patients(P = 0.003),the pre-RT TS >5.5 cm group compared to the ?5.5 cm group(P = 0.023),the mid-RT TV >11.06 cm~3 group compared to the ?11.06 cm~3 group(P < 0.0001),the TVRR ?86.7% group compared to the >86.7% group(P < 0.0001),all showed worse PFS.While the mid-RT TV >11.06 cm~3 group compared to the ?11.06 cm~3 group(P = 0.003),the TVRR ?86.7% group compared to the >86.7% group(P = 0.0004),both also showed worse LFFS.Multivariate analysis showed that OS in FIGO stage ? patients was significantly better than that in stage ? and ? patients(HR: 0.498,95%CI: 0.258-0.964,P = 0.039),and OS in mid-RT TV ?11.06 cm~3 group was significantly better than that in mid-RT TV >11.06 cm~3 group(HR: 0.220,95% CI: 0.070-0.684,P = 0.009),after Cox regression analysis adjusted for age,TS before and after EBRT and TVRR,the difference still remained statistically significant.For PFS,patients with FIGO stage II had significantly better PFS than those with stage ? and ?(HR: 0.534,95%CI: 0.309-0.923,P = 0.025)and tumor volume reduction rate(TVRR,tumor volume reduction rate)>86.7% group showed significantly better PFS than those with TVRR ?86.7% group of the patients(HR: 0.448,95%CI: 0.213-0.941,P = 0.034),Cox regression analysis adjusted for age,TS and TV before and after EBRT,the difference still remained statistically significant.Meanwhile,multivariate analysis of LFFS showed that LFFS in the group with TVRR >86.7% group was significantly better than that in the group with TVRR ?86.7%(HR: 0.226,95%CI: 0.072-0.707,P = 0.011),after adjusted for age,FIGO stage and other tumor parameters,the difference still remained statistically significant.OS-related ROC curve analysis showed that mid-RT TV was better than FIGO staging,pre-RT TV,pre-RT TS and mid-RT TS in predicting OS(P < 0.05),and TVRR was better than pre-RT TV,pre-RT TS and mid-RT TS in predicting OS(P < 0.05).PFS-related ROC curve analysis showed that mid-RT TV was better than pre-RT TS in predicting PFS(P = 0.0176).LFFS-related ROC curve analysis showed that the sensitivity,specificity and AUC value of TVRR were 80.65%,53.05% and 0.668,respectively(P < 0.0001).Moreover,among 310 patients,27 patients(8.7%)showed local failure(LF)alone,30 patients(9.7%) showed distant metastasis(DM)alone and 4 patients(1.3%)showed both LF and DM.Conclusion: Our study confirmed that FIGO stage >II and mid-RT TV > 11.06 cm~3 were independent prognostic factors for worse OS.For PFS,FIGO stage > II and TVRR ? 86.7% were independent prognostic factors for worse PFS,and TVRR ? 86.7% was also an independent prognostic factor for worse LFFS.Therefore,the tumor parameters measured by MRI during the treatment may be valuable prognostic factors with survival in women with local advanced cervical cancer receiving CCRT.