the presence of liver metastasis is one of the most important prognostic factors in patients with gastric cancer . because this has usually been considered as systemic disease ; these patients have been treated palliatively with therapy including chemotherapy , best supportive care , or admission to a clinical trial . however , their survival is far from satisfactory . in recent decades , multimodality approaches using various combinations of chemotherapy , radiotherapy , and surgery have been evaluated in patients with gastric cancer with liver metastases . many studies have shown that curative surgical resection for liver metastasis can result in long - term survival in some highly selected patients with a solitary hepatic metastasis from gastric cancer . unfortunately , most gastric cancer patients with liver metastasis are not candidates for liver surgery because they have multiple , scattered , and bilobar hepatic lesions or also have other distant metastases or extensive lymph node metastases . patients with gastric cancer and isolated liver metastasis are rare , comprising only 0.5% of patients in a series reported by linhares et al . transarterial chemoembolization ( tace ) is an alternative therapy for patients with gastric cancer and liver metastasis in whom hepatic resection can not be performed . reported the effects of tace using degradable starch microspheres after prior systemic chemotherapy ( sc ) in gastric cancer patients with liver metastasis . tace has frequently been used to treat unresectable liver metastases from gastric cancer , and the outcomes have been promising . whether combination tace therapy confers survival benefit in patients with gastric cancer and synchronous liver metastasis ( gcslm ) is still an unanswered question . to answer it , we compared the therapeutic efficacy of gastrectomy with tace plus sc ( gtc ) and sc alone ( sc ) for gcslm . this was a multicenter , ambispective , controlled cohort study . from january 2008 to december 2013 , 107 patients with gcslm attending the chinese people 's liberation army general hospital , beijing cancer hospital , peking university people 's hospital , and beijing friendship hospital undergoing gtc treatment or sc were enrolled in this study . the data were collected retrospectively from january 2008 to may 2012 and have been collected prospectively since june 2012 . we defined synchronous metastases as metastases detected before or during surgery , or those which occur within 6 months after gastrectomy . the inclusion criteria were as follows : ( 1 ) age between 18 and 75 years ; ( 2 ) clinical performance status according to eastern cooperative oncology group ( ecog ) criteria 2 ; ( 3 ) longevity > 3 months ; ( 4 ) histologically or cytologically proven primary gastric cancer ; ( 5 ) liver metastasis was examined by computed tomography ( ct ) and/or magnetic resonance imaging ( mri ) ; ( 6 ) no extrahepatic metastasis ; ( 7 ) laboratory findings within acceptable limits for undergoing gastrectomy , tace and/or sc ; ( 8) achievement of a microscopically margin - negative ( r0 ) gastrectomy ; ( 9 ) no other malignancies ; ( 10 ) no serious associated medical diseases . the exclusion criteria included : ( 1 ) longevity <3 months , ( 2 ) portal vein occlusion ; ( 3 ) passive ascites ; ( 4 ) child  pugh grade c liver function ; and the study was approved by the chinese people 's liberation army general hospital ethics committee . informed consent was obtained from all patients in the prospective cohort prior to entering the study and from all patients in the retrospective cohort at follow - up visits . gastric tube cancer group a total , distal , or proximal gastrectomy with d2 lymphadenectomy was performed , depending on the tumor location , and the metastatic lesions left untouched . negative margins were ensured to achieve a microscopically margin - negative ( r0 ) gastrectomy . the d category was evaluated in accordance with the 7 edition of the japanese classification of gastric carcinoma . depending on the size and location of the tumor and its arterial supply , a catheter was selectively inserted into the appropriate segmental feeding arteries to perform embolization with an emulsion containing pirarubicin ( 30 mg / m ) , oxaliplatin ( 130 mg / m ) , 5-fluoro - uracil ( 500 mg / m ) , and lipiodol 1030 ml ( at 12 ml / cm of the tumor diameter ) . depending on the status of the blood supply , additional embolization using 1- to 2-mm - diameter gelatin sponge particles was performed . tace was repeated at 8- to 12-week intervals for as long as the patient was able to tolerate this procedure . a follow - up abdominal ct was performed 2 months after undergoing tace to assess the treatment response . in three patients , this regimen comprised intravenous oxaliplatin ( 130 mg / m ) on day 1 , and oral capecitabine ( 1000 mgmd ) for 2 consecutive weeks followed by a 1-week rest . second - line chemotherapy based on irinotecan or paclitaxel was recommended in cases of disease progression or intolerable toxicity . systemic chemotherapy group these patients received the same chemotherapy as described above but did not undergo surgery or tace . follow - up was performed every 6 weeks during chemotherapy , every 3 months for the first 2 years , every 6 months for the subsequent 3 years and yearly thereafter . follow - up evaluation included clinical examination , standard blood chemistry , serum carcinoembryonic antigen ( cea ) concentration , serum sialyl lewis antigen ( ca19 - 9 ) concentration , abdominal ultrasound , and abdomino - pelvic ct or mri . the patient follow - up lasted until death or the cut - off date of december 31 , 2014 . two ( 1.9% ) patients were still alive and were censored at the cut - off date . tumor response to treatment was assessed according to the modified response evaluation criteria in solid tumors by a radiologist in each hospital . complete response ( cr ) was defined as disappearance of all target lesions ; partial response ( pr ) as not less than 30% decrease in the sum of diameters of viable lesions ; progressive disease ( pd ) as an increase of 20% in the sum of diameters of viable lesions or any new tumor lesion ; and stable disease ( sd ) as all cases that did not qualify as cr , pr , or pd . response rate ( rr ) was defined as complete plus pr . extent of liver metastases was classified by the japanese research society for gastric cancer , which are as follows : h1 , liver metastases limited to one lobe of the liver ; h2 , isolated metastases in both lobes of the liver ; and h3 , multiple spread of metastases in both lobes of the liver . adverse effects were recorded during treatment and for 28 days after the last dose of study medication and graded according to the national cancer institute - common toxicity criteria scale version 3.0 . clinicopathologic variables were compared between the two groups using the student 's t - test and the chi - square test . survival curves were constructed according to the kaplan  meier method and compared with the log - rank test . rates of treatment response and treatment - related adverse effects were compared by the chi - square or fisher 's exact test . prognostic variables with a significance level of p < 0.1 according to univariate analysis were entered into the model . this was a multicenter , ambispective , controlled cohort study . from january 2008 to december 2013 , 107 patients with gcslm attending the chinese people 's liberation army general hospital , beijing cancer hospital , peking university people 's hospital , and beijing friendship hospital undergoing gtc treatment or sc were enrolled in this study . the data were collected retrospectively from january 2008 to may 2012 and have been collected prospectively since june 2012 . we defined synchronous metastases as metastases detected before or during surgery , or those which occur within 6 months after gastrectomy . the inclusion criteria were as follows : ( 1 ) age between 18 and 75 years ; ( 2 ) clinical performance status according to eastern cooperative oncology group ( ecog ) criteria 2 ; ( 3 ) longevity > 3 months ; ( 4 ) histologically or cytologically proven primary gastric cancer ; ( 5 ) liver metastasis was examined by computed tomography ( ct ) and/or magnetic resonance imaging ( mri ) ; ( 6 ) no extrahepatic metastasis ; ( 7 ) laboratory findings within acceptable limits for undergoing gastrectomy , tace and/or sc ; ( 8) achievement of a microscopically margin - negative ( r0 ) gastrectomy ; ( 9 ) no other malignancies ; ( 10 ) no serious associated medical diseases . the exclusion criteria included : ( 1 ) longevity <3 months , ( 2 ) portal vein occlusion ; ( 3 ) passive ascites ; ( 4 ) child  pugh grade c liver function ; and the study was approved by the chinese people 's liberation army general hospital ethics committee . informed consent was obtained from all patients in the prospective cohort prior to entering the study and from all patients in the retrospective cohort at follow - up visits . gastric tube cancer group a total , distal , or proximal gastrectomy with d2 lymphadenectomy was performed , depending on the tumor location , and the metastatic lesions left untouched . negative margins were ensured to achieve a microscopically margin - negative ( r0 ) gastrectomy . the d category was evaluated in accordance with the 7 edition of the japanese classification of gastric carcinoma . depending on the size and location of the tumor and its arterial supply , a catheter was selectively inserted into the appropriate segmental feeding arteries to perform embolization with an emulsion containing pirarubicin ( 30 mg / m ) , oxaliplatin ( 130 mg / m ) , 5-fluoro - uracil ( 500 mg / m ) , and lipiodol 1030 ml ( at 12 ml / cm of the tumor diameter ) . depending on the status of the blood supply , additional embolization using 1- to 2-mm - diameter gelatin sponge particles was performed . tace was repeated at 8- to 12-week intervals for as long as the patient was able to tolerate this procedure . a follow - up abdominal ct was performed 2 months after undergoing tace to assess the treatment response . in three patients , this regimen comprised intravenous oxaliplatin ( 130 mg / m ) on day 1 , and oral capecitabine ( 1000 mgmd ) for 2 consecutive weeks followed by a 1-week rest . second - line chemotherapy based on irinotecan or paclitaxel was recommended in cases of disease progression or intolerable toxicity . systemic chemotherapy group these patients received the same chemotherapy as described above but did not undergo surgery or tace . follow - up was performed every 6 weeks during chemotherapy , every 3 months for the first 2 years , every 6 months for the subsequent 3 years and yearly thereafter . follow - up evaluation included clinical examination , standard blood chemistry , serum carcinoembryonic antigen ( cea ) concentration , serum sialyl lewis antigen ( ca19 - 9 ) concentration , abdominal ultrasound , and abdomino - pelvic ct or mri . the patient follow - up lasted until death or the cut - off date of december 31 , 2014 . two ( 1.9% ) patients were still alive and were censored at the cut - off date . tumor response to treatment was assessed according to the modified response evaluation criteria in solid tumors by a radiologist in each hospital . complete response ( cr ) was defined as disappearance of all target lesions ; partial response ( pr ) as not less than 30% decrease in the sum of diameters of viable lesions ; progressive disease ( pd ) as an increase of 20% in the sum of diameters of viable lesions or any new tumor lesion ; and stable disease ( sd ) as all cases that did not qualify as cr , pr , or pd . response rate ( rr ) was defined as complete plus pr . extent of liver metastases was classified by the japanese research society for gastric cancer , which are as follows : h1 , liver metastases limited to one lobe of the liver ; h2 , isolated metastases in both lobes of the liver ; and h3 , multiple spread of metastases in both lobes of the liver . adverse effects were recorded during treatment and for 28 days after the last dose of study medication and graded according to the national cancer institute - common toxicity criteria scale version 3.0 . clinicopathologic variables were compared between the two groups using the student 's t - test and the chi - square test . survival curves were constructed according to the kaplan  meier method and compared with the log - rank test . rates of treatment response and treatment - related adverse effects were compared by the chi - square or fisher 's exact test . prognostic variables with a significance level of p < 0.1 according to univariate analysis were entered into the model . relevant clinicopathological data of the patients according to the two patient groups are summarized in table 1 ( gtc therapy , 32 patients ; sc therapy , 75 patients ) . there were no significant differences between the two groups in age , sex , ecog performance status , primary gastric cancer - related factors , liver metastases - related factors , or child baseline characteristics of patients with gastric cancer and synchronous liver metastasis gtc : gastrectomy , tace , chemotherapy ; sc : systemic chemotherapy ; ecog : eastern cooperative oncology group . the 1- , 2- , and 3-year os rates in the gtc group were 62.5% , 9.9% , and 3.3% , respectively , whereas they were 21.2% , 1.5% , and 0% , respectively , in the sc group . the median os was 14 months ( 95% confidence interval [ ci ] : 13.114.9 months ) in the gtc group and 8 months ( 95% ci : 6.69.4 months ) in the sc group ; this difference is statistically significant ( p < 0.001 ) . figure 2 shows progression - free survival ( pfs ) curve for the two therapy groups . the 6- and 12-month pfs were 46.4% and 9.4% , respectively , for the patients who underwent gtc therapy , with a median pfs of 5 months ( 95% ci : 2.27.8 months ) . the 6- and 12-month pfs were 8.0% and 1.3% , respectively , for the patients who underwent sc therapy , with a median pfs of 3 months ( 95% ci : 2.33.4 months ) . the difference between the two therapy groups in pfs was statistically significant ( p < 0.001 ) . three ( 9.4% ) and 16 patients ( 50.0% ) achieved cr and pr , respectively . the overall rr in the gtc group was 59.4% . in the sc group , 2 ( 2.7% ) and the rate of response to treatment was significantly higher in the gtc than in the sc group ( p = 0.035 ) . table 2 lists treatment - related adverse effects according to treatment group and common toxicity criteria scale version 3.0 . most patients in the gtc group developed postembolization complications , including abnormal liver function , abdominal pain , fever , and nausea , within 1-month . these patients received supportive treatment with antiemetics , analgesics , and antipyretics , corticosteroids being reserved for the more severe cases . three patients in the gtc group underwent only one cycle of tace because of abnormal serum bilirubin or alanine transaminase levels . no patients in the sc group stopped treatment because of treatment - related adverse events . treatment - related adverse effects according to treatment group and common toxicity criteria scale version 3.0 * p<0.05 ; p<0.001 .  : not applicable ; gtc : gastrectomy , tace , chemotherapy ; sc : systemic chemotherapy . univariate analysis showed the following three factors to be associated with os : size of liver metastases ( p = 0.025 ) , extent of liver metastases ( p = 0.002 ) , and use of radiofrequency ablation ( p = 0.013 ) [ table 3 ] . pfs was correlated with serum cea concentrations ( p = 0.093 ) , lymph node metastases ( p = 0.045 ) , extent of liver metastases ( p = 0.001 ) , and use of radiofrequency ablation ( p = 0.009 ) [ table 4 ] . multivariate analysis revealed that size ( p = 0.037 ) and extent of liver metastases ( p < 0.001 ) were independent predictors of os . extent of liver metastases ( p = 0.003 ) was also an independent predictor of pfs [ table 5 ] . clinicopathological and treatment - related factors associated with os after gtc treatment os : overall survival ; gtc : gastrectomy , tace , chemotherapy ; cea : carcinoembryonic antigen . clinicopathological and treatment - related factors associated with pfs after gtc treatment pfs : progression - free survival ; gtc : gastrectomy , tace , chemotherapy ; cea : carcinoembryonic antigen . cox 's multivariate analysis of factors contributing to survival of the 32 patients who underwent gtc treatment  : not applicable ; cea : carcinoembryonic antigen ; ci : confidence interval ; hr : hazard ratio ; gtc : gastrectomy , tace , chemotherapy ; pfs : progression - free survival ; os : overall survival . relevant clinicopathological data of the patients according to the two patient groups are summarized in table 1 ( gtc therapy , 32 patients ; sc therapy , 75 patients ) . there were no significant differences between the two groups in age , sex , ecog performance status , primary gastric cancer - related factors , liver metastases - related factors , or child baseline characteristics of patients with gastric cancer and synchronous liver metastasis gtc : gastrectomy , tace , chemotherapy ; sc : systemic chemotherapy ; ecog : eastern cooperative oncology group . the 1- , 2- , and 3-year os rates in the gtc group were 62.5% , 9.9% , and 3.3% , respectively , whereas they were 21.2% , 1.5% , and 0% , respectively , in the sc group . the median os was 14 months ( 95% confidence interval [ ci ] : 13.114.9 months ) in the gtc group and 8 months ( 95% ci : 6.69.4 months ) in the sc group ; this difference is statistically significant ( p < 0.001 ) . figure 2 shows progression - free survival ( pfs ) curve for the two therapy groups . the 6- and 12-month pfs were 46.4% and 9.4% , respectively , for the patients who underwent gtc therapy , with a median pfs of 5 months ( 95% ci : 2.27.8 months ) . the 6- and 12-month pfs were 8.0% and 1.3% , respectively , for the patients who underwent sc therapy , with a median pfs of 3 months ( 95% ci : 2.33.4 months ) . the difference between the two therapy groups in pfs was statistically significant ( p < 0.001 ) . in the gtc group , 32 patients received 87 cycles of tace ( median of three cycles ) . three ( 9.4% ) and 16 patients ( 50.0% ) achieved cr and pr , respectively . the overall rr in the gtc group was 59.4% . in the sc group , 2 ( 2.7% ) and the rate of response to treatment was significantly higher in the gtc than in the sc group ( p = 0.035 ) . table 2 lists treatment - related adverse effects according to treatment group and common toxicity criteria scale version 3.0 . most patients in the gtc group developed postembolization complications , including abnormal liver function , abdominal pain , fever , and nausea , within 1-month . these patients received supportive treatment with antiemetics , analgesics , and antipyretics , corticosteroids being reserved for the more severe cases . three patients in the gtc group underwent only one cycle of tace because of abnormal serum bilirubin or alanine transaminase levels . no patients in the sc group stopped treatment because of treatment - related adverse events . treatment - related adverse effects according to treatment group and common toxicity criteria scale version 3.0 * p<0.05 ; p<0.001 .  : not applicable ; gtc : gastrectomy , tace , chemotherapy ; sc : systemic chemotherapy . univariate analysis showed the following three factors to be associated with os : size of liver metastases ( p = 0.025 ) , extent of liver metastases ( p = 0.002 ) , and use of radiofrequency ablation ( p = 0.013 ) [ table 3 ] . pfs was correlated with serum cea concentrations ( p = 0.093 ) , lymph node metastases ( p = 0.045 ) , extent of liver metastases ( p = 0.001 ) , and use of radiofrequency ablation ( p = 0.009 ) [ table 4 ] . multivariate analysis revealed that size ( p = 0.037 ) and extent of liver metastases ( p < 0.001 ) were independent predictors of os . extent of liver metastases ( p = 0.003 ) was also an independent predictor of pfs [ table 5 ] . clinicopathological and treatment - related factors associated with os after gtc treatment os : overall survival ; gtc : gastrectomy , tace , chemotherapy ; cea : carcinoembryonic antigen . clinicopathological and treatment - related factors associated with pfs after gtc treatment pfs : progression - free survival ; gtc : gastrectomy , tace , chemotherapy ; cea : carcinoembryonic antigen . cox 's multivariate analysis of factors contributing to survival of the 32 patients who underwent gtc treatment  : not applicable ; cea : carcinoembryonic antigen ; ci : confidence interval ; hr : hazard ratio ; gtc : gastrectomy , tace , chemotherapy ; pfs : progression - free survival ; os : overall survival . * p<0.05 , p<0.01 . approximately , 4.09.9% of gastric cancer patients have synchronous liver metastases ; the prognosis is very poor . in recent decades , surgical , interventional , and ablation treatment techniques have improved remarkably , and their use in patients with liver metastases from gastric cancer may improve prognosis . this study has shown that it is feasible to administer gtc treatment to patients with gcslm and that gtc treatment achieves better outcomes than sc treatment in such patients . several studies have shown that gastrectomy for gastric cancer with concomitant liver metastases confers survival benefits . gastrectomy achieves a median survival time of 8.016.3 months compared with 2.46.8 months without this treatment . the rationale for offering gastrectomy to patients with gcslm is that it reduces the tumor load , thus rendering the residual tumor more responsive to adjuvant treatment , decreases tumor metabolic demands , reduces the risk of potential life - threatening complications and postpones their appearance , and reduces tumor secretion of immunosuppressive cytokines . second , tace maximizes the concentration of chemotherapeutic drugs within the hepatic lesions while simultaneously minimizing systemic exposure , thus achieving greater therapeutic efficacy with less toxicity than conventionally administered chemotherapy . thus , tace can decrease the size and number of hepatic lesions . in our study , the treatment rr was 59.4% in the gtc group , which was significantly better than in the sc group ( 37.4% ) . in three patients with critical and inoperable hepatic metastases , the tumor size and number were reduced by repeated sessions of tace , after which the tumors were ablated by radiofrequency ablation . in addition , repeated tace may treat undetected micrometastases that would otherwise cause intrahepatic recurrence ; complete eradication of metastases may improve the prognosis in patients with gcslm . in our experience , tace is a minimally invasive treatment and repeated tace achieves a better prognosis . in the late stage of gastric cancer in addition to surgical resection and local control , sc is a prime option for prolonging survival . a multicenter phase iii study ( classic trial ) found that capecitabine plus oxaliplatin ( xelox ) is promising enough to become the standard first - line treatment for patients with gastric cancer who have undergone curative d2 gastrectomy . park et al . noted that xelox is effective and well - tolerated as a first - line therapy for advanced gastric cancer . capecitabine , with its mild side effects and ease of administration , has been the standard choice for adjuvant chemotherapy for advanced gastric cancer . in light of the above studies , we surmised that the xelox regimen might improve the outcomes of patients with gcslm and , therefore , chose it as the sc after gastrectomy . in our study , sc alone achieved about 37.4% rr in patients with gcslm . details of three patients who achieved long survival after tace plus radiofrequency ablation * the tnm classification according to the 7 edition of the ajcc . tace : transarterial chemoembolization ; ajcc : american joint committee on cancer ; tnm : tumor , node , metastasis ; pr : partial response ; sd : stable disease . several studies have reported that various pathological characteristics of primary gastric cancer , such as depth of tumor invasion , lymph node metastasis , and histological differentiation , are independent predictors of survival of patients with gastric cancer and liver metastases . however , these factors had no significant impact on survival in our study . the probable explanation of this apparent discrepancy is that our study focused only on gastric cancer patients with synchronous liver metastases , whereas most previous studies have included patients with both synchronous and metachronous metastases . several reports have confirmed that the number of liver metastases is a major prognostic factor . our study supported these findings : we found that the extent of liver metastases ( h1 , h2 , and h3 ) was a predictor of both os and pfs after gtc treatment . taking the present findings and those of previous reports together , the size and extent of liver metastases in patients with gcslm might be significant predictors of survival after gtc treatment . in our study , according to univariate analysis , radiofrequency ablation after tace was associated with significantly improved os and pfs . however , multivariate analysis did not identify radiofrequency ablation as a significant predictor of survival , possibly because too few patients underwent radiofrequency ablation . first , there were too few patients in the gtc group , preventing a powerful interpretation of our findings . second , this was an ambispective cohort study , with all the disadvantages associated with retrospective studies . third , depending on the treatment rr , the postoperative chemotherapy regimens were varied in some patients . fourth , the efficacy of tace with radiofrequency ablation postoperation was supposed to be compared in future study . in conclusion , the present study has shown that gastrectomy with tace plus sc is more effective in patients with gsclm than sc alone . small and few liver metastases have favorable outcomes following gtc treatment . therefore , we believe that gtc therapy prolongs survival in selected gastric cancer patients with synchronous liver metastases .
background : systemic chemotherapy ( sc ) is the recommended treatment for gastric cancer with liver metastasis . 
 however , the improvement in survival has been disappointing . 
 the aim of this study was to compare the therapeutic efficacy of gastrectomy with transarterial chemoembolization plus sc ( gtc ) and sc alone for gastric cancer with synchronous liver metastasis.methods:from january 2008 to december 2013 , 107 gastric cancer patients with synchronous liver metastasis attending the four participating centers were enrolled in this multicenter , ambispective , controlled cohort study . 
 patients who underwent gtc ( n = 32 ) were compared with controls who were received sc alone ( n = 75 ) . 
 the primary endpoints of the study were overall survival ( os ) and progression - free survival ( pfs ) . 
 the secondary endpoints were response rate to treatment and treatment - related adverse effects.results:the median os was 14.0 months ( 95% confidence interval [ ci ] : 13.114.9 months ) in the gtc treatment group and 8.0 months ( 95% ci : 6.69.4 months ) in sc group , this difference being statistically significant ( p < 0.001 ) . 
 the median pfs was significantly longer in the gtc than in the sc group ( 5 months , 95% ci : 2.27.8 months vs. 3 months , 95% ci : 2.33.4 months , respectively ) ( p < 0.001 ) . 
 the rate of response to treatment was significantly better in the gtc than the sc group ( 59.4% vs. 37.4% , respectively ) ( p = 0.035 ) . according to multivariate analysis , os in patients receiving combination treatment 
 was significantly correlated with the size ( p = 0.037 ) and extent of liver metastases ( p < 0.001 ) . 
 pfs was also correlated with the extent of liver metastases ( p = 0.003).conclusions : gtc is more effective than sc alone in patients with gastric cancer with synchronous liver metastasis . 
 gtc therapy prolongs the survival of selected gastric cancer patients with synchronous liver metastasis .