| Primary liver cancer(PLC)is one of the common gastrointestinal malignancies.It is the fifth leading cause of cancer morbidity and the second leading cause of cancer mortality worldwile,which does seriously harm to human health.Liver cancer rates are the highest in developing countries such as East-South Asia and Africa,where the hepatitis B virus(HBV)infection is the major factor.China alone accounts for more than 50%of the total number of cases and deaths.Hepatocellular carcinoma(HCC)is the most common pathological type,accounting for more than 90%of liver cancer in China.The early stage of HCC has no specific symptoms,most patients is advanced at diagnosis and progressed rapidly with poor prognosis.With the development of diagnosis and treatment skill,the efficiency and survival time of HCC have been improved,but many patients still have a poor prognosis.Portal vein tumor thrombus(PVTT)is one of the major poor prognostic factors.HCC and PVTT often indicate the high malignancy and poor prognosis.Many studies reported that the median survival time(MST)was only 2.7-4 months under the best support.There is no standard treatment for HCC with PVTT patients.The Barcelona Clinic Liver Cancer(BCLC)staging system classified the HCC with PVTT as advanced HCC(BCLC stage C),and only recommended Sorafenib as the standard treatment for advanced HCC.HCC between Asian and Western countries has high heterogeneity,and there are significant differences in the etiology,biological behavior and prognosis.Whether sorafenib can serve as a standard or initial treatment for advanced HCC with PVTT patients remains to be studied.In recent years,the rapid development of radiotherapy(RT)technology and the constant penetration of the dose in partial liver have make it possible for radiotherapy to target tumor at high dose.The NCCN guidelines have proposed RT as one of the recommended treatments for unresectable HCC.At present,many clinical studies have showed that RT is a safe and effective treatment for HCC with PVTT patients.However,so far there were no definite decisive factors about good prognosis for these patients.Radiation resistance after RT is the main reason for the failure of treatment.Radiotherapy combined with radiation sensitizer can theoretically improve the treatment effect and survival significantly.In this study,we reviewed a comprehensive retrospective analysis of HCC with PVTT patients treated with either RT or Sorafenib,to find the prognostic risk factors of survival and stratify in some factors simultaneously.Aim to provide the evidence for the individualized treatment of clinical and establish the radiotherapy combined with targeted therapy in HCC with PVTT.Part 1 Survival analysis in cases of radiotherapy to portal vein tumor thrombus in hepatocellular carcinomaObjective:Analysize retrospectively the cases of HCC and PVTT treated with radiotherapy,aimed to seek an effective independent prognostic factors and provide the evidence for individualized treatment.Methods:Patients with HCC with PVTT referred for radiotherapy in Shandong Cancer Hospital,Tai'an Central Hospital,and Hebei Harrison International Peace Hospital from January 2007 to December 2014 were retrospectively reviewed according to the inclusion and exclusion criteria.The survival time and clinical baseline characteristics before radiotherapy were investigated.PVTT was typed by Cheng's classification,and the most significant imaging change after radiotherapy was regarded as the treatment response.Survival analysis was performed by Kaplan-Meier method and Cox proportional hazard regression model.Results:1.A total of 216 patients were included in this study.All patients were treated with 3D-CRT,IMRT or IGRT.The 6 months,1 year and 2 years overall survivals were 60.1%,36.3%,and 11.9%,respectively,and the MST was 11.2 months.Cox regression model showed that viral etiology,Child-Pugh classification,D-dimer,PVTT type,target areas,radiation dose,RT response,time interval from PVTT at diagnosis to the beginning of radiotherapy,treatments after RT were independent prognostic factors for overall survival.Only 2.8%of patients suffered from Grade 3 toxicity.2.According to Cheng's classification,the MSTs of type II(101/216,46.7%),type?(82/216,38.0%),and type ?(33/216,15.3%)were 14.1 months,11.9 months,and 4.5 months,and the 1-year overall survival rates were 61.1%,49.4%,and 14.9%respectively.The statistically significant survival advantage was observed in the patients between different types of PVTT(P<0.001,HR=2.083,95%CI:1.621?3.034).There was no patient with type I in group.3.The MST of target areas included PVTT and entire HCC was 16.2 months,which was longer than that only included the PVTT of 10.3 months,and the difference was statistically significant(P=0.031,HR=1.216,95%CI:1.065?1.644).4.Objective response rate of the 216 patients was 52.3%.The MSTs were 25.9 months,15.8 months,14.3 months and 8.0 months for the CR,PR,VT,and NR group,respectively.The difference of survival was significant(P<0.001,HR=2.765,95%CI:1.960?3.736).5.Univariate and multivariate analysis all observed the statistically significant survi-val advantage in 168 patients who underwent combined treatments after the beginning of radiotherapy,the MST was 12.3 months,which was longer than 5.3 months of the RT-alone group(P=0.006,HR=1.760,95%CI:1.112?2.435).Of the 168 patients,the MST of 38 patients treated with RT and Sorafenib was 15.3 months,significantly higher than the RT-other treatments group and the RT-alone group(P = 0.032).6.The median time interval from PVTT at diagnosis to the beginning of radiotherapy was 2.6 months.The survival whose time interval was shorter than 2.6 months was significantly better than that longer than 2.6 months(MST:15.6 mo.vs.9.1 mo,P =0.001).Conclusion:Mondern Radiotherapy is effective and well-tolerated for PVTT in HCC patients.The prognosis of patients with HBV-/HCV-,Child-Pugh A,D-dimer?1 mg/L,PVTT type ?,objective treatment response,and combined treatment after radiotherapy was better.With the liver dose and liver function permitted,the recommended dose is more than 50Gy,and the recommended target areas include PVTT and entire HCC.After diagnosis of PVTT,the sooner the beginning of radiation therapy,the better prognosis.Radiotherapy could be the initial treatment option for HCC with PVTT patients.Part 2 Comparative analysis of survival in cases of radiotherapy combined with Sorafenib for hepatocellular carcinoma with portal vein tumor thrombusObjective:To compare the survival time of RT combined with Sorafenib and Sorafenib monotherapy for HCC with PVTT patients,and establish radiotherapy combined with targeted therapy in patients of HCC with PVTT.Methods:Retrospectively reviewed the HCC with PVTT patients treated with either RT or Sorafenib Shandong Cancer Hospital,Tai'an Central Hospital,and Hebei Harrison International Peace Hospital from January 2007 to December 2014.Screened out the patients treated with radiotherapy combined with Sorafenib(RT+Sor group)and sorafenib monotherapy group(Sor group),and compare the survival time of two groups.Results:1.According to the inclusion and exclusion criteria,a total of 71 patients were enrolled in this study,including 38 patients with radiotherapy combined with Sorafenib(RT+Sor group)and 33 patients with Sorafenib monotherapy(Sor group).The 6 months,1 year and 2 years overall survivals were 73.5%,44.8%and 12.7%respectively,and the MST was 11.0 months.2.MST in RT+Sor group was 15.3 months,compared with 9.9 months in Sor group.The survival difference between the two groups was statistically significant.The combined treatment of radiotherapy and Sorafenib had significant survival benefit,and the survival time of RT+Sor group was prolonged by 5.4 months compared with Sor group.Conclusion:Compared with Sorafenib monotherapy,Radiotherapy combined with Sorafenib for hepatocellular carcinoma with portal vein tumor thrombus patients can significantly improve overall survival.Radiotherapy combined with Sorafenib is recommended combination in the treatment strategy of HCC with PVTT. |
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