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esophageal cancer ( ec ) is one of the most fatal types of cancer wordwide , with 455,800 new cases and 400,200 deaths in 2012 .
esophageal squamous cell carcinoma ( escc ) is the predominant type in china , in contrast to the predominance of esophageal adenocarcinoma in the western countries , which covers more than 90% of all ec cases .
surgery remains the treatment of choice for localized cancer ; however , the prognosis is still poor . in recent years
previous studies have shown that a number of inflammatory biomarkers , such as c - reactive protein ( crp ) , neutrophil to lymphocyte ratio ( nlr ) , and platelet to lymphocyte ratio ( plr ) , were associated with prognosis in several types of cancer , including ec .
recently , the systemic immune - inflammation index ( sii ) is a useful prognostic indicator for patients with small cell lung cancer and hepatocellular carcinoma . to the best of our knowledge ,
however , no studies regarding sii in patients with ec are available . in this study , therefore , we aimed to determine the prognostic value of sii in patients with resectable escc .
a total of 298 patients with resectable escc were included in the current retrospective study from jan 2005 to dec 2008 .
the eligibility criteria were included : ( 1 ) escc diagnosed by histopathology ; ( 2 ) curative surgery for localized disease ( stage i  iii ) ; ( 3 ) without neoadjuvant treatment ; ( 4 ) without any form of acute and/or chronic inflammatory disease ; and ( 5 ) preoperative serum laboratory examination were obtained before surgery within 1 week .
the counts for neutrophil , lymphocyte , and platelet were taken within 1 week prior to surgery .
the sii was defined as follows : sii  =  neutrophil    platelet / lymphocyte . in the current study , a cancer - specific survival ( css )
chicago , il ) and r 3.2.3 software ( institute for statistics and mathematics , vienna , austria ) .
a web - based r software ( cutoff finder ) was used to determine the optimal cut - off value for sii .
cutoff finder is a freely available web application that can be accessed using an arbitrary web browser ( http://molpath.charite.de/cutoff ) .
a nomogram model was also established and the predictive accuracy was evaluated by harrell 's concordance index ( c - index ) . in the current study , p 
statistical analyses were conducted with spss 17.0 ( spss inc . , chicago , il ) and r 3.2.3 software ( institute for statistics and mathematics , vienna , austria ) .
a web - based r software ( cutoff finder ) was used to determine the optimal cut - off value for sii .
cutoff finder is a freely available web application that can be accessed using an arbitrary web browser ( http://molpath.charite.de/cutoff ) .
a nomogram model was also established and the predictive accuracy was evaluated by harrell 's concordance index ( c - index ) . in the current study , p  < 
of the total number of patients , 38 ( 12.8% ) were women and 260 ( 87.2% ) were men .
the mean values for neutrophil , platelet , lymphocyte , and sii were 4.54    1.92  ( 10/l ) , 225    74  ( 10/l ) and 750    482  ( 10/l ) , respectively .
additionally , correlation analyses showed that sii was negatively correlated with lymphocyte ( r  =  0.362 , p  <  0.001 ) and positively correlated with neutrophil ( r  =  0.620 , p  <  0.001 ) and platelet ( r  =  0.607 , p  < 
sii was negatively correlated with lymphocyte ( r  =  0.362 , p  <  0.001 ; a ) and positively correlated with neutrophil ( r  =  0.620 , p  <  0.001 ; b ) and platelet ( r  =  0.607 , p  <  0.001 ;  c ) .
the optimal cut - off value for sii was 410  ( 10/l ) according to the cutoff finder ( fig .
patients then were divided into 2 groups using the sii cut - off of 410  ( 10/l ) .
there were 81 ( 27.2% ) patients with sii  410  ( 10/l ) and 217 ( 72.8% ) patients with sii > 410  ( 10/l ) .
the relationships between sii and clinical characteristics were shown in table 1 . in the current study ,
the sii was significantly associated with tumor length ( p  =  0.006 ) , tnm stage ( p  =  0.012 ) , nlr ( p  <  0.001 ) , plr ( p  <  0.001 ) , and crp ( p  <  0.001 ) .
the vertical line designates the optimal cut - off point with the most significant ( log - rank test ) split .
the cut - off value was 410 with a sensitivity of 73.6% and a specificity of 47.1% .
patients with sii  410  ( 10/l ) had a significantly better 5-year css than patients with sii > 410  ( 10/l ) ( 51.9% vs 24.0% , p  < 
, we revealed that sii was also significantly associated with css based on the tnm stage ( fig .
in multivariate analyses , sii was an independent prognostic factor in patients with resectable escc ( p  =  0.027 ) .
however , nlr ( p  =  0.661 ) or plr ( p  =  0.064 ) were not significant independent predictors for css ( table 3 ) . in the current study , we used the crp , a well - known inflammatory indicator , in multivariate analyses .
our result revealed that crp was still an independent prognostic factor in patients with escc ( p  <  0.001 ) .
meier css curves stratified by sii . patients with sii  410  ( 10/l ) had a significantly better 5-year css than patients with sii > 410  ( 10/l ) ( 51.9% vs 24.0% , p  < 
the predictive value of sii was significant in patients based on the tnm stage ( i stage : 61.8% vs 35.0% , p  =  0.005 ; b ) , ( ii stage : 48.3% vs 27.1% , p  =  0.028 ;  c ) , and ( iii stage : 38.9% vs 17.8% , p  =  0.045 ; d ) .
css = cancer - specific survival , sii = immune - inflammation index , tnm = tumor node metastasis .
to predict the risk for patients with escc , a novel nomogram model was established by sii , crp , and tnm stage combined with age and sex ( fig .
4 ) . it can predict the probability of death for patients with escc . in the current study ,
to the best of our knowledge , this is the first report to demonstrate the prognostic role of sii in patients with resectable escc . in this study
, we revealed that sii was an independent significant predictive factor ( p  =  0.027 ) .
we performed a cutoff finder based on r software to verify to optimal cut - off value and conclude that 410  ( 10/l ) may be the optimal cut - off value for sii in predicting css in patients with resectable escc .
in addition , the current study was also the first attempt to establish a predictive nomogram model to improve predictive accuracy based on sii .
, we analyzed the prognostic role of sii in escc patients without neoadjuvant treatment mainly because neoadjuvant therapy ( chemotherapy and/or radiation ) will have an important impact on the inflammation .
previous studies have shown that nlr and plr were independent predictors of survival in various cancers , including ec . however , due to the inconsistent results , the prognostic values of nlr and plr in ec remain controversial .
recently , we conducted a meta - analysis revealed that high levels of nlr were significantly correlated with poor survival in patients with ec . in the current study
however , we demonstrated that plr , but not nlr , was an independent prognostic factor in patients with resectable escc .
sii was initially performed to indicate the host inflammatory status in patients with resectable hepatocellular carcinoma .
then , another study confirmed that sii was superior to nlr and plr as an independent factor for patients with small cell lung cancer . in the current study , we revealed that sii was a significant predictive indicator in patients with resectable escc ( p  =  0.027 ) .
however , nlr ( p  =  0.661 ) or plr ( p  =  0.064 ) were not significant independent predictors for css .
moreover , we used a cutoff finder based on r software to verify the optimal cut - off value , which was 410  ( 10/l ) compared to 330  ( 10/l ) and 1600  ( 10/l ) in previous studies .
it is well know that nomogram could establish a simple graphic representation of a statistical predictive model . in the current study , therefore , we attempt to establish a predictive nomogram model to predict the probability of the death risk for resectable escc patients based on sii , crp , and tnm stage combined with age and sex . the nomogram performed well in predicting css by the c - index ( 0.68 ) .
second , we excluded patients who had neoadjuvant chemotherapy and/or radiotherapy , which may have influenced our results .
in addition , our study revealed that sii is an independent predictive factor in patients with escc ; however , it should be kept in mind that the sensitivity and specificity looks like not very high . moreover
, the c - index showed that the nomogram model has a good accuracy but it is not perfect indicating that there is still room for improvement .
therefore , further studies are needed to illuminate the relationship between sii and prognosis in patients with resectable escc .
in summary , our study showed that sii is still a useful prognostic indicator for patients with resectable escc .
we conclude that 410  ( 10/l ) may be the optimal cut - off value for sii .
abstractthe aim of the study was to determine the prognostic role of systemic immune - inflammation index ( sii ) in patients with esophageal squamous cell carcinoma ( escc).a total of 298 escc patients were enrolled in the current retrospective study . 
 the sii was calculated by the formula : neutrophil    platelet / lymphocyte . 
 the optimal cut - off value was calculated by the cutoff finder . 
 univariate and multivariate analyses were evaluated for cancer - specific survival ( css ) . 
 additional , we also established a nomogram model to predict the prognosis for patients with escc.the optimal cut - off value was 410    109/l for sii . 
 patients with sii  410  ( 109/l ) had a significantly better 5-year css than patients with sii > 410  ( 109/l ) ( 51.9% vs 24.0% , p  <  0.001 ) . 
 multivariate analyses revealed that sii was a significant independent predictive indicator ( p  =  0.027 ) . 
 a nomogram could be more accuracy for css for patients with escc ( c - index : 0.68).the sii is a useful independent prognostic indicator for patients with resectable escc .