| [Objective]For pancreatic ductal adenocarcinoma(PDAC),a tumor with very poor prognosis,it would be significant for its integrated treatment and for increasing the long-term survival rate to accurately predict its prognosis.However not many factors allowing accurate and thorough prediction of the prognosis of PDAC have been available clinically.As tumor burden has been considered as one of the most important prognostic and predictive factors for tumors,this study was designed to analyze the prognostic value of tumor burden measured by preoperative 18F-FDG PET/CT in patients with resected pancreatic cancer and search for a method accurately evaluating the tumor burden in PDAC.At the same time,we also analysis the role of other pathological factors in PDAC.[Materials and Methods]1.Object of studyThe cases that include in this study were received preoperative 18F-FDG PET/CT examination and radical pancreatectomy in our hospital from January 2008 to April 2015.Case inclusion criteria:(1)All cases were underwent radical resection of pancreatic cancer and pathologically proven as pancreatic ductal adenocarcinoma(PDAC);(2)All cases were underwent 18F-FDG PET/CT scan and did not receive any anticancer therapy before the examination;(3)All cases have complete clinical data and follow-up data;(4)The time from 18F-FDG PET/CT examination to radical operation was less than 10 days.Case exclusion criteria:(1)The one whose operation was not radical;(2)The one died perioperatively;(3)The operation were confirmed as non R0 resection in postoperative pathology:(4)The one died not because of pancreatic cancer.At lase.there were 48 cases that include in this study.2.Equipment,imaging agent and image processing softwarePET/CT:Somatom Sensation Biography 16HR+ PET/CT(SIEMENS,Germany).RDS1111 Medical cyclotron(Crystal Technology&Industries,America)Imaging agent:18F-deoxyglucose(18F-FDG),produced by our hospital PET Center RDSI111 medical cyclotron,radiochemical purity greater than 98%,PH=7.0,after rigorous testing of sterile,non-pyrogenic,non-endotoxin.Image processing software:PACS PET/CT image storage system,RT-image image processing software(Based on the ENVI5.0+IDL8.2 application platform,provided by Stanford University.Version2.4.40)3.Materials3.1 Case collection and follow-upFactors that may influencing the prognosis of pancreatic cancer were retrospectively collected,including:age.gender,tumor location,tumor size,preoperative CA19-9,lymph node metastasis(NO,N1),pTNM stage(based on the NO.7 TNM staging criteria by AJCC),postoperative chemotherapy(YES,NO).Follow up includes outpatient-way or telephone-way.The survival time were calculated on a monthly basis from the date of operation to the date of death or follow-up deadline as of October 1,2015.3.2 Imaging methodsBefore the 18F-FDG PET/CT examination,the patient should avoid strenuous exercise within 24 hours,fasting for more than 6 hours,empty bladder and drink water 1500ml to fill the upper digestive tract.Blood sugar should not higer than 8mmol/l.The patient accepted the injection of 18F-PDG through the elbow vein in quiet state.The injection dose is 7.4 MBq/kg body weight.After the injection,the patient should have a rest in dark placee of 60mins,then accept PET/CT 3D acquisition scan(Biograph 16,120kev,50mAs).The patient accepted CT scan first and then accepted the same range of PET image acquisition by the same pose.The sequence and range of scanning is from perineal region to head.The patient take a deep breath at the end of the breath,holding on and accepting three phase enhanced scanning of pancreas(bolus tracking)+ with the sequential chest(1 mm and 5 mm reconstruction),abdomen(1 mm and 5 mm reconstruction)and pelvic(1 mm and 5 mm reconstruction),head(2mm and 5mm)sequentially in the same machine.After 2.5--3 hours of intravenous injection of 18F-FDG,the Patient accept the PET 18F-FDG/CT delayed imaging scan.At last,the CT images and PET images are stored in PACS PET/CT system in the DICOM format.3.3 Image analysis and PET/CT parameter acquisition.Put the CT images and PET images into RT-image processing software to conduct image tissue attenuation correction and image fusion and obtain the coronal,sagittal and transverse CT images,PET images and PET/CT fusion images.Firstly,analysis the images by vision to search for suspicious pancreatic lesions,outline the appropriate region of interest(ROl)in the most concentrated area of 18F-PDG.The maximum standardized uptake value SUV max of 18F-PDG is calculated automatically by the computer workstation from the ROI.Then,use 50%SUVmax as the threshold to outline the target ROI layer-by-layer.At the same time,the computer automatically calculates and records the area Si,the layer thickness Ti and the average SUV uptake value SUVmeani of the target ROI.Finally,Metabolic tumour volume(MTV)and total lesion glycolysis(TLG)were calculated according to the following formulas:MTV=nΣh=1Si×Ti,TLG=Σi=1Si×Ti×SUVmeani.3.4 Statistical analysisStatistical analysis was performed using SPSS 19.0 statistical software(IBM).Categorical variable such as sex.tumor location.lymph node metastasis.pTNM stage,postoperative chenmotherapy and continuous variable such as age,tumor size,preoperative serum SUVmax.CA19-9,MTV,TLG were all analyzed in two classified variable form.The cut-off value of age is 60 year-old.The cut-off value of CA19-9,tumor size,SUVmax.MTV,TLG were thier median.The relationships between MTV,TLG and other clinical pathological factors were analysed by Pearson’s chi-square test or Fisher’s exact test.The differences in survival between the groups were compared using Kaplan-Meier method and log-rank tests,.The Cox proportional hazards model was used to analyze the relationships between MTV,TLG and other clinical pathological factors and the prognosis of pancreatic cancer in the univariate survival analysis and the multivariate survival analysis,and to search for independent risk factors influencing the prognosis of pancreatic cancer,and to calculate the relative hazard ratio(HR)and its 95%confidence interval(CI).[Results]1.Basic clinical informationTotal 48 cases of patients were put into research,of which 33 are males and 15 are females,whose ages distribute between 35 and 81 with an average age of(61.4±11.8);.Their tumor sizes range from 1.0 to 7.0cm,averaging(3.4± 1.4)cm,the median size is 3.2cm;38 cases are of pancreatic head cancer,and the rest 10 cases are of pancreatic tail cancer;24 cases are of lymph nodes transfer(N1),24 cases are of(NO);CA19-9 averages(328.1 ± 339)U/ml,the median is 245U/ml;14 cases are at pTNM phase I,28 cases are at phase Ⅱ,zero cases are at stage Ⅲ and stage Ⅳ;22 patients received chemotherapy after surgery,26 patients did not receive chemotherapy after surgery,the mean SUVmax is 5.3 ± 2.4,the median is 4.7;MTV averages(38.4 ± 32.2)cm3 with the median of 25cm3;TLG averages 168.0 ±32.2cm3 with the median of 78cm3.2.The relationship between TLG,MTV and general clinical pathological factorsAll continuous variables such as age,tumor size,preoperative CA19-9,SUVmax,MTV and TLG were grouped into two groups:high-low or large-small group.All variables were all analvzed into two classified variable form.X2 test analysis showed that MTV was not associated with age,sex,lymph node metastasis,pTNM stage,preoperative CA19-9.postoperative chemotherapy and SUVmax(P>0.05).but was correlated with Tumor size and tumor location(P<0.05).It means that with the increase of tumor size,the MTV is higher.It also means that the MTV of carcinoma of head of pancreas was significantly higher than that of carcinoma of the pancreatic body and tail.Similarly,TLG was not associated with age,sex,lymph node metastasis.pTNM stage.preoperative CA19-9,postoperative chemotherapy and SUVmax(P>0.05).but was correlated with histological grades,clinical stages and lymph node metastasis status(P<0.05).The results also showed that MTV was significantly correlated with TLG(P=0.000).3.Survival analysis3.1 Basic survival after resectionThe follow-up time of all patients ranged from 3 to 60 months.There were 28 patients died,the proportion was 58.3%.The average survival time was 19 months and the median survival time was 22 months.3.2Kaplan-Meier survival analysisIn Kaplan-Meier survival analysis,one and two year overall survival rates of high MTV group were 60.5%and 22.2%,but one and two year overall survival rates of low MTV group were 86.8%and 65.4%.The difference of overall survival rates between the two groups was statistically significant(P=0.019).one and two year overall survival rates of high TLG group were 59.7%%,29.8%,and one and two year overall survival rates of low MTV group were 90.3%,67.0%.The difference of survival rate between the two groups was more significant(P=0.001).The analysis also showed that the postoperative survival rate of patients between different levels of tumor size,pTNM stage,preoperative CA19-9 and were significantly different(P=0.011,0.008,0.009).But to different levels of gender,age,tumor location,lymph node metastasis,preoperative chemotherapy,their survival rate were not statistically significant(P>0.05).3.3 COX univariate survival analysisThe COX univariate analysis indicated that high Tumor size,pTNM stage,preoperative CA19-9,MTV,TLG were statistically significant risk predictors of poor OS(P=0.015,0.013,0.013,0.024,0.003)。But patient’s gender,age,tumor location,lymph node metastasis,postoperative chemotherapy and SUVmax had no significant effect on the prognosis of the patients(P>0.05).3.4 COX multivariate survival analysisAs the significant relevance of MTV and TLG,we put MTV,TLG along with other prognostic factors shown to be significant in univariate Cox analysis to COX multivariate survival analysis.Following adjustment for other factors,TLG was shown to be an independent risk factor for the prognosis of the PDAC patients(P=0.006),the relative risk(HR)of patients with high-level TLG is 3.990 times of patients with low-level TLG.The analysis also indicated pTNM stage and perioperative CA19-9 as independent risk factors for the prognosis of the PDAC patients(P>0.05).But after adjust for the other factors,MTV and tumor size were not shown to be independent predictors for prognosis of pancreatic cancer(P>0.05).[Conclusions]Preoperative CA19-9 level and pTNM stage are closely correlated with the prognosis of PDAC.Preoperative 18F-FDG PET/CT showed high prognostic value for pancreatic cancer.The tumor burden indicators(MTV and TLG)determined by 18F-FDG PET/CT could accurately reflect the tumor burden,and allow better prediction of the survival of PDAC patients,with TLG being an independent risk factor for the postoperative prognosis of PDAC patients.As higher TLG is likely to indicate shorter survival,more active integrated treatment should be given postoperatively for patients with higher TLG determined by preoperative PET/CT. |
PDF Full Text Request