Comparision Of The Effects Of Treatment In Advanced HCC With TACE In Combination With Sorafenib By EASL And MRECIST

BackgroundHepatocellular carcinoma (hepatic cellular carcinoma, HCC) accounted for the most common primary liver cancer. This is the sixth most common malignancy in the global cause of death from cancer, after lung and stomach cancer. Liver cancer because most patients found in late, has been unable through surgical resection. Infected with Hepatitis B, hepatitis C virus is a risk factor for liver cell gene cancerous.Liver disease is common in China.The development of imaging technology allows smaller tumors (diameter<1cm) can be detected, and accurate repeated measurements have also been improved. This technique can also reflect changes in tumor density. When the tumor volume is not reduced tumor density change is also reflected an indicator of treatment efficacy is very important. With the development of new drugs, limited cytogenetic small molecular targeted drug to enter clinical, these unlike cytotoxic drugs so that the tumor volume is reduced, but it can inhibit the growth of tumor cells so that the tumor cell apoptosis. Alone using RECIST criteria to evaluate these drugs in clinical trials did not show anticancer activity, although they displayed on the absence of disease progression and survival of benefit.Patients with unresectable hepatocellular carcinoma (HCC), a variety of local treatment of hepatocellular carcinoma, which via the hepatic artery chemoembolization (Tanscatheter arterial chemoembolization, TACE) is the preferred treatment method, and can obtain a better short-term effect, but the treatment method can only lead to most of necrosis of the tumor the early hypoxia environment will cause increased production of vascular endothelial growth factor (vascular endothelial growth factor, VEGF), promoting the re-growth of the tumor vasculature, which is one of the important reasons of tumor complex. Sorafenib in advanced hepatocellular carcinoma in patients with no other treatment (such as surgery and topical treatment) system for the treatment of the standard medication. Sorafenib is a multikinase inhibitors, anti-angiogenesis, as anti-tumor growth and regulation of the immune. Based on the positive results of the randomized controlled trials with advanced hepatocellular carcinoma Phase III, in Europe, the United States and other countries have been approved as standardization of new drugs for the treatment of unresectable hepatocellular carcinoma.In assessing response to treatment, survival is still the end of Phase III clinical trials, while the use of radiological methods to assess the response to treatment is widely used in the surrogate endpoint of the Phase II clinical trial assessing response to therapy and predict survival of cancer research key. The traditional method of assessing the efficacy the RECIST criteria measuring changes in tumor size to assess response to therapy; This method is based on measuring the value of the target lesion unidirectional diameters and. With the range of treatment methods, the application of the clinical anticancer drugs, recent studies have shown poor correlation with the clinical benefit, the correctness of the assessment of tumor response to treatment of these standards being challenged; e.g. TACE induced decrease in tumor blood vessels, tumor necrosis the effects can not always be associated with tumor size parallel. In2000, convened by the European Association for the Study of Liver Diseases (EASL) liver cancer expert group revised the evaluation criteria recommended in the enhanced scan imaging to measure tumor enhanced area as the best method of assessing response to therapy. In2008, the Association of the American Society for the Study of Liver Diseases (AASLD) has developed a set of guidelines, which includes formal changes made RECIST1.1criterion, designed to determine the effective assessment of tumor concept proposed CT radiology and MR dynamic contrast-enhanced lesions enhanced arterial phase scan for effective assessment of the lesions, the degree of enhancement of the tumor in the arterial phase into reference standard-mRECIST criterion.Purposes1. The research objective was to compare by RECIST, EASL, mRECIST radiology tumor treatment response assessment methods CT scan of consistency at an early point in time. Determine whether the target lesion efficacy of alternative overall.2. efficacy and survival of the contact of the target lesions and total lesion assessment whether there are differences.3. Determine which method of these methods can provide better prognostic information in early treatment follow-up.Materials and Methods1. Patients with the inclusion and exclusion criteriaFrom February2008to February2011in our hospital received sorafenib combined with TACE for hepatocellular carcinoma44patients were collected, and eliminate13does not meet the requirements of the patients;3patients after TACE received radiofrequency ablation treatment;2patients in the TACE surgery manipulation of different chemotherapy drugs;4patients because of the short follow-up period or incomplete image is also excluded4patients failed to complete the follow-up treatment for economic reasons. The remaining31patients with the TACE palliative care patients to comply with the requirements of this study. TACE Inclusion criteria included:chronic liver disease, liver function Child-Pugh score A/B Used in combination with sorafenib treatment inclusion criteria:ECOG PS score2points or2points or less, Child-Pugh score A or B, platelets>104/ul, hemoglobin8.5g/L,. BCLC staging of all patients is B or C phase.HCC patients are diagnosed with major imaging methods, controversial was diagnosed by needle biopsy.2. Treatment programsAll patients from February2008to February2011line sorafenib in combination with TACE treatment, super-selective catheterization of the right hepatic artery left hepatic artery infusion chemotherapy was given. Infused chemotherapy and embolization. Exceed liquefied B lipiodol chemotherapy drugs fully mixed into the emulsion. Ultra-micro-catheter be inserted into the tumor feeding artery. The mixture is slowly injected through the catheter to the target vessel. The volume of lipiodol is5-20ml. Feeding artery significantly enlarged liver cancer patients in lipiodol emulsion bolt Saihou Jia particulate embolic agents (such as gelatin sponge or microspheres). After TACE, five days take sorafenib treatment, each400mg, twice daily. Such as the emergence of drug side effects interrupts treatment or reduces the dose. Patients continue treatment until death or treatment interruption encounter one of the following criteria:serious adverse events, disease progression and ECOG score of4points, deterioration of liver function or consensus rut eliminate treatment. Standard liver function cannot continue to treat total bilirubin>3mg/dl for4weeks discontinued treatment.3. Treatment response assessmentIndividual checks before and after treatment, to assess multilayer spiral CT scanning and gadolinium enhanced MR scan.28patients with contrast-enhanced CT scan to assess the remaining three patients were evaluated with MR. All patients underwent TACE before surgery within a week had CT dynamic contrast-enhanced scan, follow-up review RECIST1.1of EASL, mRECIST standard assessment of tumor response by reference to the point in time the results of CT or MR examination.Treatment response assessment EASL, RECIST1.1, mRECIST guidelines. EASL standard enhanced dynamic CT and MR scanning artery to determine the uptake of the contrast agent can be an effective measurement of tumor lesions, and to measure tumor strengthen regional dual diameter multiplied and. RECIST1.1and is based on the measured values of the lesion largest single diameter lesions, while mRECIST arterial phase the lesions single diameter measured values of and.Three radiographic evaluation of the target lesion response and overall lesion response records mapping each reaction. Two or more measurable lesions definited the target lesion in RECIST1.1, and mRECIST, while the EASL you to define all arterial phase of measurable lesions. The assessment does not consider the changes in the non-target lesion target lesion response to any changes in the emerging lesions and extrahepatic. In contrast, the overall reaction intrahepatic measure two or more measurable lesions, but also consider the change of the non-target lesions and new lesions and liver lesions. Tumor response including complete response (measurable lesions completely disappeared), partial response (EASL defined lesions dual diameters product and a50%reduction,30%reduction in RECIST1.1mRECIST defined lesion diameters and single), disease progression (the EASL definition of lesions dual-diameter line and the product of a25%increase in RECIST1.1mRECIST defined lesion diameters of the stable disease (20%) increase in the PR and PD). We determine the overall response to the target lesion and non-target lesions, including reference to the above criteria.two of the seniority of radiologist blinded to assess the response to treatment in patients with HCC. Differences in the response assessment in patients with two physicians to review and reach a consensus decision.The overall response rates refer to the total CR and RP, disease control rate with reference to the total CR, PR and SD.4. follow-upWe define the minimum treatment period is2months. Over8weeks of treatment, patients continued oral sorafenib6-8weeks with RECIST1.1, of EASL, and mRECIST assess the efficacy of treatment.5. Statistical methodsKappa test to the consistency between the three methods used to determine the K coefficient greater than0.75is a good agreement between the two methods. The chi-square test determined the difference for categorical variables for comparison. The difference between response and no response survival by Cox regression analysis and Kaplan-Meier survival analysis log-rank test assessed according to the treatment of the EASL, RECIST1.1, mRECIST standard evaluation. COX proportional hazard model was used to assess baseline factors and the overall survival rate of contact. A p-value less than0.05indicates the presence of a statistically significant difference. Subsequently used to create a multivariate model, the p-value of<0.1for the criteria for inclusion. All data are SPSS13.0statistical analysis software.Result31patients met the conditions,29men and2women, median age is52years (range31-78years). More than half of the patient’s physical condition ECOG score of0(18/31,58%) and the majority of patients with Child-Pugh score A (25/31,80%).80%(25/31) of patients with multiple tumor focus. HCC patients with BCLC staging,58%(18/31) of the patients were divided into B period, divided into stage C,42%(13/31) of patients because of the physical condition score of1or2points. All patients had varying degrees of liver cirrhosis. Finally, in the bit AFP value is23416kU/L (range:2-237347U/L), and31patients with cisplatin-based TACE. Radiographic evaluations ago patients average chemoembolization treatment. Lipiodol embolization to the first imaging assessment scan a median time of51days (range:42-61days), compared RECIST1.1, EASL and mRECIST the response rate significantly different. The RECIST1.1of EASL, and mRECIST overall and target lesion response rate (CR+PR) was10%,55%,52%and13%,61%,61%, respectively. The overall response of Four patients to evaluation by RECIST1.1, EASL and mRECIST is partial response. Wherein mRECIST rating is PR15patients, only4patients RECIST1.1assessed as PR, the remaining patients were assessed as SD10mRECIST. EASL assessed as SD patients a patient RECIST1.1are determined for PD. The EASL and mRECIST to assessment of PD patients are almost identical. The overall reaction The only difference is that an EASL rating for PR in patients with mRECIST named SD. This phenomenon should be because mRECIST considered only enhance the long axis of the tumor measurements. EASL is the enhanced tumor two long-path and the product. Target lesion response assessment of four patients have different results. Target lesion of two patients was assessed as complete response by EASL and mRECIST. The phenomenon should EASL and mRECIST consider all arterial phase lesions. mRECIST only consider two target lesions. In addition, the EASL standard assessment partially effective in patients will be mRECIST to standard classification for the SD. Three imaging assessment methods target lesion response and overall lesion reaction. Target lesions reaction alone compares overall response, disease control rate (CR, PR and SD) higher partial response to treatment can be expected disease. Disease control rates were80%and72%of the RECIST1.1overall response and target lesion response of EASL, and mRECIST overall response and disease control of the target lesion response rates were83%. Kaplan-Meier analysis of the general reaction of the EASL and mRECIST assessment and the mitigation of the target lesion response and response exists the difference was statistically significant. Cox regression analysis and evaluation of each method associated with survival show mRECIST is strong protective factors, the risk ratio was0.056.ConclusionThe results of this study suggest that RECIST1.1standard does not apply to the assessment of the therapeutic effect of TACE combined with sorafenib treatment of hepatocellular carcinoma. The hepatocellular carcinoma TACE combined with sorafenib treatment of hepatocellular considers lipiodol embolism and anti-VEGF drugs on tumor and possible image performance. Although the EASL and mRECIST assess the therapeutic effect of TACE combined with sorafenib hepatocellular carcinoma has a high degree of consistency, but mRECIST measurement method is simple, it is recommended to use.The EASL and mRECIST assessment standards in TACE combined with sorafenib treatment after6to8weeks of dynamic CT and MRI scans can be a more accurate assessment of TACE combined with sorafenib treatment survival of patients with hepatocellular carcinoma. The results of this study show the mRECIST method and EASL and patient survival of high correlation. Patients with unresectable hepatocellular carcinoma by TACE combined with sorafenib at early time points after treatment with RECIST1.1standard evaluation results and survival in patients with low correlation. Therefore the EASL and mRECIST Standard further guide clinical treatment of a certain value, also confirmed that the method can be used as the end point of the phase Ⅱ clinical trial.