Early Response Evaluation Of Anti-angiogenesis Therapy In Metastatic Colorectal Cancer By Contrast Enhanced Ultrasound

Background and Aim: As first-line treatment for metastatic colorectal cancer(m CRC),many researches have shown that the combination of anti-angiogenesis targeted agents,such as Bevacizumab, plus chemotherapy can significantly improve the clinical effects and prolong the survival time of patients. However, early response evaluation of anti-angiogenesis therapy is still short of unified indicators or testing tools. Response Evaluation Criteria In Solid Tumors( RECIST), which accesses tumors curative effect mainly according to the size changing of tumors after treatment 2-3 months, is at present used to evaluate response of anti-angiogenesis targeted therapy. anti-angiogenesis targeted therapy leads to tumors necrosis by affecting tumors blood perfusion, however, there is no evident influence on the size of tumor, so RECIST is not the best way to evaluate early response of anti-angiogenesis targeted therapy; on the other hand, anti-angiogenesis targeted therapy has the disadvantage of high costs, long periods of treatment and high toxicity, therefore, there is in urgent need of early prediction method to replace current way of evaluation response after 2-3 moths treatment. Contrast Enhanced Ultrasound(CEUS) has shown a good potential application prospect at predicting response of anti-angiogenesis targeted therapy since it can better display lesions blood perfusion.Thus,this study, aims to explore the application value of the noninvasive contrast Enhanced ultrasound(CEUS) in predicting early response of anti-angiogenesis therapy in metastatic colorectal cancer, was designed strict. This study was approved by local ethics committee and registered in Chines Clinical Trial Registry(Chi CTR)(Registaation ID:Chi CTR-DOD-15006262).Method: Between April 2015 and March 2016, 30 consecutive patients with colorectal liver metastasis(CRLM) were enrolled and confirmed by endoscopy,histological and imaging examination.14 patients received the combination treatment of bevacizumab and chemotherapy, another 16 patients are treated with chemotherapy alone.All patients underwent CEUS before treatment(the 1st day) and before the second cycle(the 15 th day) of treatment. Four parameters according to quantitative analysis software,peak intensity(PI), time to peak(TTP), area under curve(AUC) and wash in slope(Pw),are measured and correlated with liver lesions' blood perfusion. All patients were classified as responders or non-responders according to Response Evaluation Criteria In Solid Tumors 1.1(RECIST 1.1). T-test and other statistical approaches were used to analyze the difference of quantitative parameters between responders and non-responders.This study also intended to compare the discrepancy and clinical value of CEUS in predicting early the response of anti-angiogenesis and chemotherapy therapy in metastatic colorectal cancer.Results: There is no significant change with the longest diameters of liver target lesions of30 patients in the early stage of treatment(about 15 days) comparing with the baseline level(the mean of difference:0.09±0.25 cm, P=0.274), however, tumors blood perfusion has changed remarkably. The baseline level of Pw of liver target lesions was higher in responders than non-responders both treated with bevacizumab and chemotherapy(1.25±0.57vs0.55±0.25 d B/s,P=0.039); moreover, the percentage of difference of PI and Pwvalue before and after treatment of liver target lesions showed marked statistical significance between those responders and non-responders(P=0.002 and 0.01). There is no significant change with PI and Pw between responders and non-responders accepted chemotherapy alone(P>0.05). No statistical significance of difference of TTP and AUC was detected between responders and non-responders treated with bevacizumab combination chemotherapy or chemotherapy alone.Conclusion: CEUS can predicate early the response of of anti-angiogenesis therapy in metastatic colorectal cancer,at the 15 th day of treatment, before tumor size changed,whereas it has little value in early response evaluation of chemotherapy alone in metastatic colorectal cancer.