Prognostic Value Assessment Of Pretreatment ¹⁸F-FDG PET/CT Lean Body Mass-corrected Parameters In Patients With Hepatocellular Carcinoma

Objective:Hepatocellular carcinoma（HCC）is a malignant tumor with high mortality worldwide.Therefore,the early diagnosis and prognosis are crucial to the tumor treatment decision making.Nowadays,among the various global HCC staging systems,Barcelona Clinic Liver Cancer（BCLC）staging system as the predictors of overall survival（OS）,was verified to be the best prognostic stratification system for HCC.However,its predictive value in every condition was suspected,and some investigators believed it could be improved by adding some other factors into the system.Recently,fluorine-18-fluorodeoxyglucose(¹⁸F-FDG)positron emission tomography（PET）/computed tomography（CT）is an effective examination in tumor diagnosis and staging,therapy response surveillance,and recurrence detection.Related studies showed that standardized uptake value（SUV）,tumor-to-normal liver uptake ratio（TLR）,metabolic tumor volume（MTV）,total lesion glycolysis（TLG）,etc.,had considerable prognostic values in patients with HCC.However,those studies only investigated the prognostic value of ¹⁸F-FDG PET/CT parameters based on body weight（BW）,and nearly no study evaluated the parameters with lean body mass（LBM）correction in patients with HCC.Some investigations reported that parameters derived from LBM could better describe the ¹⁸F-FDG PET/CT quantitative indices than the ones normalized to BW,especially in the obese patients.Furthermore,the PET Response Criteria in Solid Tumors（PERCIST）also recommended using the LBM-corrected parameters recently.Therefore,in this study,we collected the pretreatment ¹⁸F-FDG PET/CT parameters based on both LBM and BW in patients with HCC with all TNM stages,and investigated their prognostic values together with the HCC staging systems and clinically related factors to identify whether the pretreatment ¹⁸F-FDG PET/CT LBM-corrected parameters could predict OS better than the others.Furthermore,some studies reported that the routine PET/CT imaging acquired one hour after the ¹⁸F-FDG injection was not sufficient for the tumor detection,and they recommended the delayed PET/CT imaging at two hours and three hours after the¹⁸F-FDG injection.Currently,the delayed PET/CT imaging studies only investigated the diagnostic value of BW-corrected parameters in patients with HCC.To our knowledge,no previous delayed ¹⁸F-FDG PET/CT imaging study evaluated the diagnostic and prognostic value of LBM-corrected parameters in patients with HCC.Consequently,in this study,we acquired the pretreatment dual-time-point ¹⁸F-FDG PET/CT LBM-corrected parameters,and appraised their predictive significance for OS together with the BCLC staging system and the correlative clinical factors,to explore the prognostic value of delayed ¹⁸F-FDG PET/CT LBM-corrected parameters in patients with HCC,and which imaging acquisition time point could provide the better predictive significance.Then,more valuable ¹⁸F-FDG PET/CT reference indexes could be further provided to patients and clinicians for the diagnosis and prognosis of HCC.Methods:1.We retrospectively analyzed the pretreatment ¹⁸F-FDG PET/CT images of61 patients with HCC and measured both LBM-corrected and BW-corrected PET/CT parameters,including MTV,maximal SUV of the tumor(SUV_max),TLG,TLR,and so on.Additionally,we obtained the clinical characteristics data as followings:age,sex,hepatitis virus infection type,cirrhosis,ascites,hepatic encephalopathy,treatment type,tumor number,tumor size of the maximal one,vascular invasion,TNM stage,tumor grade,Child-Pugh class,BCLC staging,Okuda staging,serumα-fetoprotein,total bilirubin,albumin,creatinine,alkaline phosphatase,alanine transaminase（ALT）,aspartate transaminase（AST）,and international normalized ratio.Furthermore,the event and OS data of the patients were also collected by the follow-up.The prognostic value of those factors for OS was assessed by the SPSS statistical software.The continuous variable was cut into the dichotomous variable by the optimal cutoff value,which was computed through the receiver-operating characteristic（ROC）curve analysis and maximally selectedχ²-statistics.Cox proportional hazards regression test was used to predict the statistical significance of variables in univariate and multivariate analyses.Paired-sample t-test and Pearson correlation coefficient were applied to determine the difference and correlation between variables.Kaplan-Meier survival analysis with log-rank test was utilized to illustrate the associations between independent prognostic factors and the OS.2.We retrospectively analyzed the pretreatment dual-time-point ¹⁸F-FDG PET/CT images of 46 patients with HCC and measured the PET/CT LBM-corrected parameters one hour and three hours after the ¹⁸F-FDG injection,such as LBM-corrected SUV_max(lbmSUV_max),TLR,MTV,LBM-corrected TLG,and so on.Meanwhile,the patients’demographics,body index,and clinical characteristics were also collected as following variables:age,sex,weight,height,hepatitis virus infection type,cirrhosis,treatment type,tumor grade,BCLC staging,creatinine,ALT,AST.Moreover,the event and OS data of the patients were obtained by the follow-up.The predictive significance of those indicators was assessed by the SPSS statistical software,and the analytical approach was similar to the previous methods.Furthermore,the time-dependent trends and differences of PET/CT parameters in each BCLC staging subgroup were elucidated by the figures created by GraphPad Prism software.Results:1.In the prognostic value research of pretreatment ¹⁸F-FDG PET/CT LBM-corrected and BW-corrected parameters in patients with HCC,the univariate analysis indicated that the PET/CT parameters with both corrected methods,ascites,serumα-fetoprotein,alkaline phosphatase,AST,tumor number,tumor size of the maximal one,vascular invasion,TNM stage,Child-Pugh class,BCLC staging,and Okuda staging were significant predictors of OS.However,in multivariate and Kaplan–Meier analyses,only lbmSUV_max more than 3.35 g/ml,AST more than 42.00 U/l,and BCLC staging B–C were significant independent predictors of poor OS.When BCLC staging variable was stratified by four categories instead of two in the multivariate analysis,it was not the statistically significant independent predictor anymore,but lbmSUV_max and AST still were.2.In the prognostic value research of pretreatment dual-time-point ¹⁸F-FDG PET/CT LBM-corrected parameters in patients with HCC,the univariate analysis results demonstrated that AST,BCLC staging,and dual-time-point ¹⁸F-FDG PET/CT LBM-corrected parameters were significant predictors for OS.However,in multivariate and Kaplan-Meier analyses,only lbmSUV_max obtained one hour after FDG injection(lbmSUV_max1h)higher than 3.65 g/ml,and AST greater than 46.19 U/l were significant independent predictors of poor OS.By contrast,none of PET/CT parameters obtained three hours after injection was the independent prognostic factor for OS,and neither was the BCLC staging.Additionally,in the comparison of dual-time-point PET/CT parameters using the BCLC staging system,TLR values increased significantly with time in both BCLC staging 0-A group（n=19）and B-C group（n=27）.Conclusion:Pretreatment ¹⁸F-FDG PET/CT LBM-corrected parameters can predict the OS in patients with HCC.Moreover,lbmSUV_max and AST,as the independent predictors of OS,could supplement the prognostic value of the BCLC staging system.Furthermore,pretreatment dual-time-point ¹⁸F-FDG PET/CT LBM-corrected parameters had significant prognostic value in patients with HCC.Finally,although the delayed imaging could visualize the HCC lesion more effectively,lbmSUV_max1h as the independent prognostic factor for OS and the actual FDG uptake of the whole tumor,surpassed the prognostic worth of other LBM-corrected parameters obtained in the dual-time-point PET/CT imaging.