soft tissue sarcomas are relatively rare kind of tumors with variety of presentations which arise from the mesenchyme , which can be derived from different types of tissue such as smooth muscle , bone , lymph , adipose tissue , or vascular tissues . although comprising only 1% of all cancers , soft tissue sarcoma is difficult to diagnose and treat because of its diversity , and with 5-year mortality rate as high as 50% . soft tissue sarcoma can be diagnosed by computed tomography ( ct ) and magnetic resonance imaging ( mri ) . however , ct and mri have limited capability in assessment of biological activity , malignant capacity , or potential metastatic process of tumors . as an advanced clinical imaging technique , the fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography ( f - fdg pet - ct ) has shown high sensitivity , specificity , and safety to evaluate glucose metabolism of tumors for early diagnosis , staging , and monitoring of potential malignancies . maximum standardized uptake value ( suvmax ) , refers to the radioactivity of imaging agent in tumor , is the most widely used semiquantitative parameter . metabolic tumor volume ( mtv ) , the tumor volume with high metabolic activity above a predefined suv threshold ( 2070% ) , is a semiquantitative parameter that integrates the metabolism and volume . and total lesion glycolysis ( tlg ) , the entire amount of tumor 's glycolysis , is also applied to represent the tumor malignant transformation . in particular , suvmax is regarded as a limited parameter that can only represent the tumor activity and fail to signify the whole tumor volume . however , there also existed studies which concluded that the volumetric parameter of pet - ct may not provide significant prognostic information . nevertheless , the overall analysis of the association between suvmax , mtv , or tlg and prognosis in soft tissue sarcoma has not been systematically and scientifically assessed . therefore , we performed a meta - analysis in order to attain a more comprehensive estimate of the prognostic value of suvmax , mtv , and tlg in predicting overall survival ( os ) and progression - free survival ( pfs ) in patients with soft tissue sarcoma by combining data from relevant studies . articles were identified about the assessment of pet - ct in prognosis of sarcoma by searching pubmed and embase until july 31 , 2016 . the used terms include  soft tissue sarcoma  ;  pet  or  pet - ct  or  positron emission tomography  ;  prognosis  ;  suvmax  or  maximum standardized uptake value  ;  mtv  or  metabolic tumor volume  and  tlg  or  total lesion glycolysis .  we performed all the analyses based on previously published studies , thus no ethical approval was required . the inclusion criteria can be read as follows : studies which included patients with soft tissue sarcoma ; studies which investigated the correlation between parameter of pet - ct ( suvmax , mtv , or tlg ) and survival outcome ( os or pfs ) ; studies which calculated the hrs and their 95% confidence interval ( ci ) for os , pfs or can be calculated on key information by using methodology of tierney et al from original articles . the exclusion criteria for this meta - analysis includes : studies which analyzed different kinds of tumors without specific results of soft tissue sarcoma ; studies which lacked prognostic information of association between parameter of pet - ct ( suvmax , mtv , or tlg ) and survival results ; studies were other types of research , such as letters and case reports ; or studies were non - english articles . main information were extracted from included studies according to predefined tables , which were divided into pretreatment and posttreatment table and included the primary information : survival endpoints , containing os and pfs and the additional information : first author , publication year , country , patients characteristics ( age , disease subtype , and histological grade ) , study design , cut - off values of suvmax , mtv , or / and tlg . we used remark criteria which consists of 20 items in sum to estimate the quality of articles . the reporting recommendations are comprised of 4 major aspects based on framework of articles : introduction , materials and methods , results , and discussion , which also contains several subdirectories in terms of specimen characteristics , analysis and presentation , and so on . each characteristics according to remark criteria accounted for 5% of scores of a study and the quality scores ranged from 0% to 100% . hazard ratio ( hr ) was used to measure the correlation between suvmax with pfs and os , which are shown in table 2 . we calculated these loghr and standard error ( se ) on the basis of following ways when either of the 2 groups of data were available : hr and 95% ci directly provided by the studies , the p - value from log - rank test and the number of patients and events by estimating the kaplan the meta - analysis of suvmax was also performed in each subgroup , which was classified by histological grade . the fixed effect model was selected when there existed no significant heterogeneity ( p    0.10 , i    50% ) in the results of the literature studies . and we used a random effect model if heterogeneity was significant ( p  <  0.10 or i  >  50% ) . an hr  >  1 without the 95% ci overlapping 1 indicated that patients with high suvmax not beneficial for patients survival while an hr  <  1 implied that the low suvmax related with worse survival outcome . survival outcomes were also assessed by odd ratio ( or ) in terms of 1- , 3- , and 5-year os and pfs , which are shown in table 2 . when the direct data of original articles were not available , or could be calculated by estimating the survival rates on kaplan  meier curves through engauge digitizer 4.1 . the publication bias was estimated by means of begg test performed on stata 11.0 and p  >  0.05 represents no significant publication bias . articles were identified about the assessment of pet - ct in prognosis of sarcoma by searching pubmed and embase until july 31 , 2016 . the used terms include  soft tissue sarcoma  ;  pet  or  pet - ct  or  positron emission tomography  ;  prognosis  ;  suvmax  or  maximum standardized uptake value  ;  mtv  or  metabolic tumor volume  and  tlg  or  total lesion glycolysis .  we performed all the analyses based on previously published studies , thus no ethical approval was required . the inclusion criteria can be read as follows : studies which included patients with soft tissue sarcoma ; studies which investigated the correlation between parameter of pet - ct ( suvmax , mtv , or tlg ) and survival outcome ( os or pfs ) ; studies which calculated the hrs and their 95% confidence interval ( ci ) for os , pfs or can be calculated on key information by using methodology of tierney et al from original articles . the exclusion criteria for this meta - analysis includes : studies which analyzed different kinds of tumors without specific results of soft tissue sarcoma ; studies which lacked prognostic information of association between parameter of pet - ct ( suvmax , mtv , or tlg ) and survival results ; studies were other types of research , such as letters and case reports ; or studies were non - english articles . main information were extracted from included studies according to predefined tables , which were divided into pretreatment and posttreatment table and included the primary information : survival endpoints , containing os and pfs and the additional information : first author , publication year , country , patients characteristics ( age , disease subtype , and histological grade ) , study design , cut - off values of suvmax , mtv , or / and tlg . we used remark criteria which consists of 20 items in sum to estimate the quality of articles . the reporting recommendations are comprised of 4 major aspects based on framework of articles : introduction , materials and methods , results , and discussion , which also contains several subdirectories in terms of specimen characteristics , analysis and presentation , and so on . each characteristics according to remark criteria accounted for 5% of scores of a study and the quality scores ranged from 0% to 100% . hazard ratio ( hr ) was used to measure the correlation between suvmax with pfs and os , which are shown in table 2 . we calculated these loghr and standard error ( se ) on the basis of following ways when either of the 2 groups of data were available : hr and 95% ci directly provided by the studies , the p - value from log - rank test and the number of patients and events by estimating the kaplan the meta - analysis of suvmax was also performed in each subgroup , which was classified by histological grade . the fixed effect model was selected when there existed no significant heterogeneity ( p    0.10 , i    50% ) in the results of the literature studies . and we used a random effect model if heterogeneity was significant ( p  <  0.10 or i  >  50% ) . an hr  >  1 without the 95% ci overlapping 1 indicated that patients with high suvmax not beneficial for patients survival while an hr  <  1 implied that the low suvmax related with worse survival outcome . survival outcomes were also assessed by odd ratio ( or ) in terms of 1- , 3- , and 5-year os and pfs , which are shown in table 2 . when the direct data of original articles were not available , or could be calculated by estimating the survival rates on kaplan  meier curves through engauge digitizer 4.1 . the publication bias was estimated by means of begg test performed on stata 11.0 and p  >  0.05 represents no significant publication bias . the initial search contained 63 studies from pubmed databases and embase did not provide with additional studies . and after 7 duplicate articles were excluded , another 39 studies were excluded by screening the titles and abstracts , 17 articles were remained for full texts reviewed . the studies which analyzed prognostic values of bone and soft tissue sarcoma without specific results of soft tissue sarcoma ware excluded . and 6 of these articles were excluded because survival outcome lacked or can not be calculated and 2 studies only contained the posttreatment survival results were included to assess the prognostic capacity of pet - ct for therapeutic response . finally , a total of 11 studies with 582 patients were included , which all reported the prognostic value of suvmax , mtv , or / and tlg for survival in soft tissue sarcoma ( fig . all 11 studies indicated high suvmax , mtv , or / and tlg represented a worse prognosis than patients with low numerical value . in terms of association between pet parameters and os and pfs , there are 7 studies that only provided with prognostic information about suvmax and 4 studies analyzed prognostic value of mtv and tlg . seven studies ( 439 patients ) in total were involved and represented a hr of 2.40 ( 95% ci : 1.384.17 , p  = result of begg test represented no evident publication bias ( z  =  1.80 , p  =  0.072 ) ( fig . the more significant hr and less heterogeneity were presented in a group of patients ( 3 studies , 154 patients ) among which the percentage of histological high grade sts  >  70% ( hr  =  4.44 , 95% ci : 2.448.08 , i  =  0% , p  =  0.91 ) ( table 2 ) . there existed 2 studies ( 140 patients ) , whose proportion of histological high grade sts was less than 70% and subgroup analysis based on those studies revealed the smaller hr and greater i ( hr  =  1.49 , 95% ci : 0.713.14 , i  =  76% , p  =  0.04 ) ( table 2 ) . forest plots of hazard ratio ( hr ) for overall survival ( os ) and progression - free survival ( pfs ) of pretreatment pet . meta - analysis of the association between suvmax and os ( a ) , suvmax and pfs ( b ) , mtv and os ( c ) , tlg and os ( d ) . forest plots of hazard ratio ( hr ) for overall survival ( a ) and progression - free survival ( b ) of posttreatment suvmax . the combined or on 1- , 3- , and 5-year os were 8.35 ( 95% ci : 4.0517.19 ) ( fig . heterogeneity existed according to 5-year os ( i  =  64% , p  =  0.04 ) and there was no significant heterogeneity in 1- and 3-year os . forest plots of odd ratio ( or ) for overall survival ( os ) and progression - free survival ( pfs ) of pretreatment suvmax . meta - analysis of the association between suvmax and 1-year os ( a ) , 3-year os ( b ) , 5-year os ( c ) , 1-year pfs ( d ) , and 3-year pfs ( e ) . funnel plot of potential publication bias for overall survival of pretreatment suvmax . in this comparison pfs was better with low suvmax patients in comparison with patients with high suvmax ( hr  =  2.20 , 95% ci : 1.473.30 , i  =  0% , significant publication bias was not existed according to begg test ( z  =  1.04 , p  =  0.296 ) . the analysis of or on 1-year and 3-year pfs involved 2 studies while the 5-year pfs only involved one study , and or with 95% ci were 2.52 ( 1.046.10 ) ( fig . significant prognostic value of mtv for os was reflected in the analysis of 3 studies including 111 patients ( hr  =  3.20 , 95% ci : 1.715.98 ) ( fig . 2c ) . and the heterogeneity ( i  =  10% , p  =  0.33 ) and publication bias ( z  =  1.04 , p  =  0.296 ) were insignificant in the assessment . meanwhile , the combined hr of tlg for os according to 3 studies ( 111 patients ) in the analysis was 5.20 ( 95% ci : 2.3411.56 ) ( fig . the pooled hr showed the significant survival advantage for low tlg over high tlg patients with sarcoma . and there was no obvious proof of heterogeneity ( i  =  0% , p  =  0.57 ) and publication bias ( z  =  1.04 , p  =  0.296 ) . the analysis of prognostic value of mtv and tlg for pfs only contained one study ( 66 patients ) . and the hrs were 3.22 ( 95% ci : 1.198.75 ) for mtv and 4.81 ( 95% ci : 1.5115.28 ) for tlg , respectively . there were 2 studies ( 149 patients ) about posttreatment suvmax for os and three studies ( 184 patients ) about posttreatment suvmax for pfs involved in the comparison , and the pooled significant hr were 2.25 ( 95% ci : 1.333.80 ) ( fig . moreover , the significant heterogeneity in os and pfs analysis were not found ( i  =  0% , p  =  0.49 ; i  =  41% , p  =  0.18 ) . seven studies ( 439 patients ) in total were involved and represented a hr of 2.40 ( 95% ci : 1.384.17 , p  =  0.0001 , i  =  79% ) ( fig . result of begg test represented no evident publication bias ( z  =  1.80 , p  =  0.072 ) ( fig . the more significant hr and less heterogeneity were presented in a group of patients ( 3 studies , 154 patients ) among which the percentage of histological high grade sts  >  70% ( hr  =  4.44 , 95% ci : 2.448.08 , i  =  0% , p  =  0.91 ) ( table 2 ) . there existed 2 studies ( 140 patients ) , whose proportion of histological high grade sts was less than 70% and subgroup analysis based on those studies revealed the smaller hr and greater i ( hr  =  1.49 , 95% ci : 0.713.14 , i  =  76% , p  =  0.04 ) ( table 2 ) . forest plots of hazard ratio ( hr ) for overall survival ( os ) and progression - free survival ( pfs ) of pretreatment pet . meta - analysis of the association between suvmax and os ( a ) , suvmax and pfs ( b ) , mtv and os ( c ) , tlg and os ( d ) . forest plots of hazard ratio ( hr ) for overall survival ( a ) and progression - free survival ( b ) of posttreatment suvmax . the combined or on 1- , 3- , and 5-year os were 8.35 ( 95% ci : 4.0517.19 ) ( fig . heterogeneity existed according to 5-year os ( i  =  64% , p  =  0.04 ) and there was no significant heterogeneity in 1- and 3-year os . forest plots of odd ratio ( or ) for overall survival ( os ) and progression - free survival ( pfs ) of pretreatment suvmax . meta - analysis of the association between suvmax and 1-year os ( a ) , 3-year os ( b ) , 5-year os ( c ) , 1-year pfs ( d ) , and 3-year pfs ( e ) . pfs was better with low suvmax patients in comparison with patients with high suvmax ( hr  =  2.20 , 95% ci : 1.473.30 , i  =  0% , significant publication bias was not existed according to begg test ( z  =  1.04 , p  =  0.296 ) . the analysis of or on 1-year and 3-year pfs involved 2 studies while the 5-year pfs only involved one study , and or with 95% ci were 2.52 ( 1.046.10 ) ( fig . significant prognostic value of mtv for os was reflected in the analysis of 3 studies including 111 patients ( hr  =  3.20 , 95% ci : 1.715.98 ) ( fig . 2c ) . and the heterogeneity ( i  =  10% , p  =  0.33 ) and publication bias ( z  =  1.04 , p  =  0.296 ) were insignificant in the assessment . meanwhile , the combined hr of tlg for os according to 3 studies ( 111 patients ) in the analysis was 5.20 ( 95% ci : 2.3411.56 ) ( fig . 2d ) . the pooled hr showed the significant survival advantage for low tlg over high tlg patients with sarcoma . and there was no obvious proof of heterogeneity ( i  =  0% , p  =  0.57 ) and publication bias ( z  =  1.04 , p  =  0.296 ) . the analysis of prognostic value of mtv and tlg for pfs only contained one study ( 66 patients ) . and the hrs were 3.22 ( 95% ci : 1.198.75 ) for mtv and 4.81 ( 95% ci : 1.5115.28 ) for tlg , respectively . there were 2 studies ( 149 patients ) about posttreatment suvmax for os and three studies ( 184 patients ) about posttreatment suvmax for pfs involved in the comparison , and the pooled significant hr were 2.25 ( 95% ci : 1.333.80 ) ( fig . the significant heterogeneity in os and pfs analysis were not found ( i  =  0% , p  =  0.49 ; i  =  41% , p  =  0.18 ) . standard uptake value ( suv ) was consistently related with metabolic rate of fdg ( mrfdg ) in soft tissue sarcoma , which makes suv a feasible way of detecting tumor malignancy . and suvmax , most widely reported , was considered as potential prognostic indicator in patients with sarcoma according to previous studies . however , only providing information about the maximum value of a single voxel volume , suvmax fails to measure the volume , burden , and heterogeneity of tumors with the shortcoming of reflecting significant prognostic value . and volumetric measurements such as mtv and tlg , representing the whole metabolic volume , may have the capability to overcome limitations of suvmax tlg is influenced by suv and mtv , and suv as well as tumor volume have an impact on mtv , moreover , suv itself can also vary with influencing factors . however , there are several contradictions existing in included studies of this meta - analysis . there existed a study which reported significant association between pretherapeutic higher suvmax , higher mtv , higher tlg and poorer os in patients with synovial sarcoma . however , in another study , suvmax was regarded as a significant independent prognostic marker for os in sts while mtv and tlg failed to provide with significant prognostic information . on the contrary , 1 article reported the superiority of tlg being a more accurate predictor than mtv or suvmax for pfs in patients with sts . according to the proposed prognostic factor categories of hayes et al , a hr greater than 2 might be regarded as a strong prognostic factor while a moderate or weak prognostic factor would be defined as a hr of 1.5 to 2.0 and < 1.5 , respectively . therefore , in this meta - analysis , the suvmax represented significant prognostic value for os and pfs on soft tissue sarcoma , whose hrs were 2.40 ( 95% ci : 1.384.17 ) and 2.20 ( 95% ci : 1.473.30 ) , respectively . of seven studies in which multivariate analysis about suvmax for os was conducted , four showed that suvmax was independent prognostic marker . and in two of three studies , suvmax was considered as independent prognostic factor for pfs . meanwhile , the mtv and tlg both represented significant prognostic value for os on soft tissue sarcoma , whose hrs were 3.20 ( 95% ci : 1.715.98 ) and 5.20 ( 95% ci : 2.3411.56 ) . however , due to the small amount of included articles , whether mtv and tlg were significant prognostic factors of pfs still needs further study . the meta - analyses compared odds ratios ( or ) on 1- , 3- , and 5-year of suvmax for os and pfs . results demonstrated the correlation between survival outcome and pet parameters . according to the combined or based on 1- , 3- , and 5-year os and pfs , high suvmax was associated with worse short- and long - term survival outcome and lesser survival benefit in patients with sarcoma . combined with the conclusion in previous section , not only can suvmax be prognostic marker but also may be used as predictors of survival or progression for both short and long term . histological grade systems applied in included studies were consist of the french federation of cancer centers sarcoma group ( fnclcc ) grading system , the grade system established by hasegawa et al . by comparison , we found the survival results of suvmax for os and pfs were associated with higher risk among patients with high grade sts at higher proportion . these differences may probably be due to the many different histological types and large variation of malignancy of soft tissue sarcoma . however , since that the related studies were too scanty to draw any conclusion , more large - scale studies are requisite to assess whether pet - ct shows unequal prognostic accuracy based on varied subgroups with soft tissue sarcoma . since pet - ct can be also used for monitoring the response of treatment in patients with sts , the posttreatment suvmax can be regarded as a factor to prognosticate therapy response . the meta - analyses of posttreatment suvmax for os and pfs were statistically significant , and the hrs were 2.25 ( 95% ci : 1.333.80 , i  =  0% , p  =  0.49 ) and 2.87 ( 95% ci : 1.814.55 , i  =  41% , widely used for evaluating therapy response of solid tumor , recist criteria divides tumor response into cr , pr , sd , and pd by measuring the tumor size based on the maximum length . in consideration of the significant relation between suvmax and survival outcome , pet - ct may be suggested as a promising tool to monitoring therapy response and marker of follow - up in patients with sts since the metabolic activity rather than morphologic information provided , which could exert an influence on the choice of surgical strategy and treatment . significant heterogeneity was found when suvmax predicts os ( i  =  79% , p  =  0.0001 ) ( fig . we made efforts to reduce the heterogeneity , and after the study ( hr  =  1.11 , 95% ci : 0.981.24 ) is excluded , the i and chi - square value were reduced from 79% to 0% and 28.54 to 4.92 . there were patients with synovial sarcoma alone in the study , which may explain the insignificant differences in os . in fact , soft tissue sarcoma is a kind of heterogeneous disease ; the tumor can be derived from many types of tissue varying from place to place . moreover , the patient heterogeneity such as different histological types , grades , and stages , the data selection , acquisition , and calculation , and clinical treatment such as surgery , neoadjuvant chemotherapy , and radiotherapy , are all important and inevitable factors account for the heterogeneity between studies . first , the meta - analysis was limited in published articles in english , that language bias may exist . furthermore , due to the general low incidence of soft tissue sarcoma , only a few articles can be used for the analysis , and the studies available to analyze the prognostic values of suvmax , mtv , and tlg were much fewer , which may influence the reliability of results . thus considering the heterogeneity existed in the results , the small quantities of included studies and the retrospective design , larger and high - quality prospective studies especially related to volumetric parameters need to be conducted for evaluation of the prognostic value of pet - ct in soft tissue sarcoma . in summary , the present meta - analysis demonstrated that the pretreatment suvmax , mtv , and tlg from f - fdg pet - ct are significant prognostic markers for os . the pet - ct can be effective tool in identifying high - risk patients with sarcoma referring to disease progression and patients survival . the results suggested that patients showing high suvmax , mtv , or tlg may be related with poor survival . and the analysis for posttreatment suvmax suggested pet - ct as a promising equipment in monitoring therapy response .
abstractbackground : considering the clinical importance of high 5-year mortality , we performed a meta - analysis of maximum standardized uptake value ( suvmax ) , metabolic tumor volume ( mtv ) , and total lesion glycolysis ( tlg ) from 18f - fdg pet - ct for overall survival ( os ) and progression - free survival ( pfs ) in patients with soft tissue sarcoma.methods:the search and selection of eligible articles was conducted on pubmed and embase . 
 we applied hazard ratio ( hr ) and odd ratio ( or ) to measure the correlation between suvmax , mtv , and tlg with pfs and os . 
 the suvmax was analyzed through subgroup in terms of histological grade and hr of posttreatment suvmax was also assessed.results:eleven studies with 582 patients were included . 
 the pooled hrs of pretreatment suvmax were 2.40 ( 95% ci : 1.384.17 ) for os and 2.20 ( 95% ci : 1.473.30 ) for pfs . 
 the hrs in terms of os were 3.20 ( 95% ci : 1.715.98 ) based on mtv and 5.20 ( 95% ci : 2.3411.56 ) based on tlg . 
 meanwhile , the predict results of pretreatment suvmax on or remained significant and the hrs of posttreatment suvmax were 2.25 ( 95% ci : 1.333.80 ) for os and 2.87 ( 95% ci : 1.814.55 ) for pfs.conclusions:the pretreatment suvmax , mtv , and tlg of 18f - fdg pet - ct showed significant prognostic value for os and the pet - ct can be used in identifying high - risk patients about progression and survival . 
 the analysis for posttreatment suvmax suggested pet - ct as a promising equipment in monitoring therapy response .