Clinical Evaluation Of Tumor Vascular Normalization Induced By Endostar In Nasopharyngeal Carcinoma Patients Via Contrast- Enhanced Ultrasonography

Objective: In order to exert the best synergistic effect of anti-angiogenesis combined with other treatment methods,it is very important to confirm the presence and the exact range of the tumor vascular normalization window.The purpose of this study was to evaluate the existence and the specific range of the vascular normalization window induced by Endostar in patients with nasopharyngeal carcinoma(NPC)via contrast-enhanced ultrasonography(CEUS),so as to provide clinical basis for optimizing the modality of Endostar combined with radiotherapy and chemotherapy for NPC.Also,the clinical application of CEUS in the evaluation of tumor vascular normalization was assessed.Methods: A total of 30 previously untreated patients with stage Ⅲ–ⅣA NPC were enrolled in the present study and were randomly divided into Endostar(ES)group(n=15)and normal saline(NS)group(n=15).The patients in the ES group were administered Endostar with normal saline intravenously,while the patients in the NS group were administered normal saline daily for 5 days.All patients underwent CEUS on the day before the administration and on days 3 and 5 subsequently.The Audio Video Interleave(AVI)of each CEUS examination was analyzed quantitatively using the CHI-Q software.Several parameters were investigated,such as peak intensity(PI),time to peak(TTP),and mean transit time(MTT).Through the comprehensive analysis of this series of related parameters,the tumor vascular normalization effect induced by Endostar in nasopharyngeal cacinoma patients was evaluated.Results: The values of PI,TTP,and MTT differed significantly at the three different time points in the ES group(all P<0.001),but not in the NS group(all P>0.05).In the ES group,PI values first increased and subsequently decreased,whereas TTP values,as well as MTT valuses,lessened initially and then increased within the 5 days after administration of Endostar.The maximum value of PI and the minimum value of TTP,as well as MTT,occurred on day 3(all P<0.05).Furthermore,the values of PI,TTP,and MTT were similar prior to the administration of Endostar in both groups(all P>0.05).However,the PI values of the ES group were significantly higher(P<0.05),whereas the TTP values and the MTT values were significantly lower following administration of Endostar(all P<0.05)compared with the corresponding parameters of the NS group.The effect of Endostar on tumor vascular normalization in nasopharyngeal carcinoma patients was evaluated by comprehensive analysis of these quantitative parameters.Conclusion: In this study,within the 5 days after the start of Endostar medication,CEUS related parameters of patients treated with Endostar showed wave-like variations.These variations confirmed that Endostar had the effect of inducing tumor vascular normalization in NPC patients,and the time window was about 5 days after the start of medication.These findings provided a clinical basis for further optimizing the modality of anti-angiogenesis therapy combined with radiotherapy and chemotherapy for NPC.In addition,this study also suggests that CEUS provides a potential mean for the clinical evaluation of tumor vascular normalization.