The Study Of Radiotherapy For Liver Cancer:Sorafenib Maintenance Following Radiotherapy And The Determination Of Internal Target Volume With4DCT

Part Ⅰ:Maintenance of sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma:a phase Ⅰ studyObjective:To investigate side-effect, toxicity, safety and feasibility for locally advanced hepatocellular cell carcinoma (HCC) treated by TACE and3DCRT/IMRT followed by Sorafenib as maintenance. The efficacy of the combined therapy was also evaluated.Matirial and Methods:Patients should be histologically or cytologically confirmed HCC and locally advanced HCC. They received one to three cycles of TACE, and then3DCRT/IMRT irradiation therapy4-6weeks later. For the patients whose tumors were not progressing maintenance of Sorafenib would be administered4to6weeks after the completion of radiotherapy. Sorafinib dose was400mg, p.o., twice a day. Sorafenib were continuously given for12months unless intolerable toxicities and/or tumor progression. Primary endpoints were side-effect and toxicity scored by CTCAE version3.0. The secondary endpoints were tumor response assessed by Response Evaluation Criteria in Solid Tumor, version1.1, time to progression (TTP), and overall survival (OS).Results:From September2009to March2011,15patients were enrolled. All patients received TACE with a median cycle of2(1-3). Radiotherapy was given to12patients with non-progression disease after TACE. After the completion of radiotherapy,7patients finally received sorafinib and5were withdrawn due to patient own decisions in2patients, acute liver injury and not recovered in1patient, intrahepatic lesion progression in1patient and lung metastasis in1patient. The most common adverse effects of TACE were fever (20%), abdominal pain (53%) and omitting (47%). During radiotherapy no patients experienced grade3-4of adverse events.2patients developed acute liver injury later. During sorafenib maintenance three patients had grade3adverse effects, which included one case of thrombocytopenia, one case of HFSR, one case of diarrhea. Other adverse effects were grade1and grade2.6patients (86%) had HFSR;5patients (71%) had diarrhea;2patients (29%) had anorexia;2patients (29%) had fatigue;2patients (29%) had hypertension.4patients (57%) needed dose reduction. Adverse effects causing dose reduction included1case (14%) of HFSR,2cases (29%) of diarrhea and1case (14%) of fever.4patients (57%) needed dose reduction. Three patients ended sorafenib,1patient had disease progression. Of all the seven patients2patients (2%) had partial response,4patients stable disease and one patient disease progression.Conclusions:Combined therapy of TACE, radiotherapy and sorafenib was well-tolerated in patients with locally advanced HCC with no severe side-effects and toxicity and good tolerance. During maintenance of sorafinib more than half patients needed dose reduction due to the toxicity. Adverse events of sorafenib included hand-foot skin reactions, diarrhea and fatigue, etc. Purpose:to determine what was the optimum projection phase for delineation of internal target volume (ITV) when4-dimensional CT (4-DCT) was used and to evaluate its feasibility and accuracy in hepatocellular carcinoma and metastatic liver cancers.Materials and Methods:4-DCT images were taken from15consecutive patients (4hepatocellular carcinomas;11hepatic metastases). We used five approaches to determine these ITVs:(1) ITVAllPhase:contouring gross target volume (GTV) on each of ten respiratory phases of4D-CT data set and fusing these GTVs to form ITV;(2) ITV2Phase:contouring GTV on the extreme respiratory phases (0%phase:peak inhalation,50%phase:peak exhalation) and fusing two GTVs to become ITV;(3) ITVMIP:contouring GTV on maximum intensity projection (MIP) of4-D CT dataset;(4) ITVMinIP:contouring the GTV on minimum intensity projection (MinIP) of4-D CT dataset;(5)ITV2M:fusing ITVMIP and ITVMinIP-ITVAllPhases was utilized as the reference ITV. The endpoints, including target volumes, matching indices (MI) and extent of under or over-estimated volumes of the respective ITVs were compared to determine the optimum projection phase and to valuate its feasibility and accuracy. The tumor size and tumor motion were also taken into account for it.Results:The values of target volume, MI and extent of under-estimated volume all indicated that ITV2M were closest to ITVAllPhase.The differences of those values between ITV2M and ITV2Phases were significant with P values of0.007,0.004and0.001, respectively. There was a good correlation between tumor size and motion and the definition of ITV using ITV2Phases, but ITV2Mwas not.Conclusions:ITV2M was recommended as the optimum projection phase in4-DCT image to determine ITVs in liver cancers with good feasibility and accuracy.