Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy

Background

Determining the resectability of locally advanced pancreatic cancer (LAPC) after induction chemotherapy is complex since CT-imaging cannot accurately portray tumor response. We hypothesized that CA19-9 response adds to RECIST-staging in predicting resectability of LAPC.

Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma

AIM： To evaluate the clinical value of serum CA19-9 levels in predicting the respectability of pancreatic carcinoma according to receiver operating characteristic （ROC） curve analysis.
METHODS： Serum CA19-9 levels were measured in 104 patients with pancreatic cancer which were possible to be resected according to the imaging. ROC curve was plotted for the CA19-9 levels. The point closest to the upper left-hand corner of the graph were chosen as the cut-off point. The sensitivity, specificity, positive and negative predictive values of CA19-9 at this cut-off point were calculated.
RESULTS： Resectable pancreatic cancer was detected in 58 （55.77%） patients and unresectable pancreatic cancer was detected in 46 （44.23%） patients. The area under the ROC curve was 0.918 and 95% CI was 0.843-0.992. The CA19-9 level was 353.15 U/mL, and the sensitivity and specificity of CA19-9 at this cutoff point were 93.1% and 78.3%, respectively. The positive and negative predictive value was 84.38% and 90%, respectively.
CONCLUSION： Preoperative serum CA19-9 level is a useful marker for further evaluating the resectability of pancreatic cancer. Obviously increased serum levels of CA19-9 （〉 353.15 U/mL） can be regarded as an ancillary parameter for unresectable pancreatic cancer.     

Post-adjuvant chemotherapy CA19-9 levels predict prognosis in patients with pancreatic ductal adenocarcinoma: A retrospective cohort study

BackgroundCarbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC.MethodsA total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL.ResultsMedian RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p < 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p < 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was >1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value.ConclusionsThe present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.     

血清CA19-9水平术前评估胰腺癌可切除性的临床价值

目的 评价血清CA19-9水平在胰腺癌术前可切除性评估中的临床价值.方法 测定52例术前影像学提示有手术切除可能性并经手术活检或术后病理确诊的胰腺癌患者术前血清CA19-9水平,以手术能否切除为金标准,绘制CA19-9的受试者工作特征(ROC)曲线,并以敏感度和特异度之和最大点即曲线左上方作为相应截断点测CA19-9的敏感度、特异度及阳性、阴性预测值.结果 52例胰腺癌患者中手术切除29例(55.8%),未切除23例(44.2%).手术切除组患者血清CA19-9水平为(159.6±170.9)U/ml,未切除组患者为(944.4±773.4)U/ml;CA19-9的ROC曲线下面积0.918(＞0.9),P＜0.01,95%可信区间0.843～0.992,左上方截断点CA19-9值为353.2 U/ml.以此为标准,敏感度93.1%,特异度78.3%,阳、阴性预测值分别为84.4%和90.0%.结论术前血清CA 19-9水平可作为影像学提示有手术切除可能的胰腺癌患者进一步评估的辅助指标.     

Serum level of TSGF, CA242 and CA19-9 in pancreatic cancer

AIM: To establish a method to detect the expression of the tumor specific growth factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of pancreatic cancer. METHODS: ELISA and Biochemical colorimetric assay were used to detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52 pancreatitis patients and 96 pancreatic cancer patients. RESULTS: The positive likelihood ratios of TSGF, CA242 and CA19-9 were 5.4, 12.6 and 6.3, respectively, and their negative likelihood ratios were 0.10, 0.19 and 0.17, respectively. With single tumor marker diagnosed pancreatic cancer, the highest sensitivity and specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when all of them were positive, the sensitivity changed to 77.0% and the specificity and the positive predictive value were 100%. The levels of TSGF and CA242 were significantly higher in the patients with pancreatic cancer of head than those in the patients with pancreatic cancer of body, tail and whole pancreas, but the expression of CA19-9 had no correlation with the positions of the pancreatic cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly higher than CA242 and CA19-9. CONCLUSION: The combined use of TSGF, CA242 and CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis. And it shows that it plays an important role to differentiate positions and tissue typing. It is a forepart diagnosis for the pancreatic cancer by combination checking. There is very important correlation between the three markers and the pancreatic cancer.     

Can preoperative CA19‐9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma?

Background: We aimed to explore the predictive ability of preoperative carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) levels for assessing tumor resectability (R0 resection) in patients with pancreatic adenocarcinoma. Methods: The present study included 72 patients who had been treated surgically for potentially resectable pancreatic adenocarcinoma and 42 patients who had been treated surgically for palliation (bypass surgery) at our institution. Pancreatic adenocarcinoma was histologically confirmed by pathological examination of the resected specimen or, if unresected, by intraoperative biopsy. Results: For resectable disease, the mean and median values of CA19‐9 were significantly lower than for R1/2 or unresectable disease. The best cut‐off points for CEA, CA19‐9, and tumor size to predict resectability were 2.47 ng/mL, 92.77 U/mL and 11.85 cm³, respectively. A CA19‐9 ≥ 92.77 U/mL and both tumor markers no less than the cut‐off levels predicted the possibility of R1/2 or unresectability with 90.6% and 88.6% accuracy, respectively. However, either tumor marker or both tumor markers less than the cut‐off levels predicted the probability of R0 resection only with 27.1% and 40.6% accuracy, respectively. The independent contributing factors to resectability (R0 resection) by multivariate regression analysis were a CA 19‐9 < 92.77 U/mL, a tumor size < 11.85 cm³, and a less advanced AJCC stage. Conclusion: The present study demonstrates that preoperative serum CA19‐9 and CEA levels can be used for the prediction of resectability (R0 resection) in patients with pancreatic adenocarcinoma, which may enable a simple and cost‐effective exclusion of such patients who are unlikely to benefit from surgery.     

Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer

BackgroundRecently, several preoperative proinflammatory markers and nutritional factors such as neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) have been reported as significant predictor for poor prognosis of various malignant tumors. In this study, we evaluated the prognostic values of these preoperative parameters in patients with resectable pancreatic head cancer.MethodsWe retrospectively reviewed consecutive patients who underwent PD for pancreatic head cancer between 2007 and 2012. A total of 46 patients were enrolled in this analysis. Preoperative parameters such as CRP, CA19-9, NLR and PNI at the time of presentation were recorded as well as overall survival. Cancer specific survival was assessed using Kaplan–Meier method. Univariate and multivariate Cox regression models were applied to evaluate the prognostic relevance of preoperative parameters. The correlations between CA19-9 values, NLR and pathological findings, first recurrence site were respectively reviewed.ResultsIn multivariable analysis preoperative high NLR (≧2.7) and high CA19-9 (≧230) were independent prognostic factors for poor survival (P value: 0.03 and 0.025, respectively). Kaplan–Meier survival analysis demonstrated the overall 2-year survival rate in patients with high NLR or high CA19-9 were 37.5% compared with 89.9% in patients with low NLR and low CA19-9.ConclusionPreoperative NLR and serum CA19-9 offer significant prognostic information associated with overall survival following PD in the patients with pancreatic head cancer.     

Analysis of prognostic factors for borderline resectable pancreatic cancer after neoadjuvant chemotherapy: the importance of CA19-9 decrease in patients with elevated pre-chemotherapy CA19-9 levels

BackgroundNeoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel.MethodsFrom 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors.ResultsEighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)].ConclusionIn patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.     

Tumor growth kinetics by CA 19-9 in patients with unresectable pancreatic cancer receiving chemotherapy: A retrospective analysis

BackgroundRecently, measures of tumor growth kinetics calculated by carbohydrate antigen 19-9 (CA 19-9) determinations after cytotoxic chemotherapy (CHT) have been reported as effective prognostic indicators in locally-advanced unresectable and metastatic pancreatic adenocarcinoma (mPDAC). The study aims to evaluate the prognostic role of tumor kinetics measured by CA 19-9 in patients with mPDAC, measuring it by three different ways.MethodsPatients with mPDAC receiving a first-line CHT between 2009 and 2017 were identified, and those for whom CA 19-9 data were available were enrolled. Three CA 19-9-related variables were calculated: CA 19-9 related reduction rate (RR) and tumor growth rate (G), after 8 weeks of CHT, tumor growth and inflammation index (TGII), after 90 days of CHT. The relationships with the outcome were analysed, and a Cox model has been build with each of the three variables.ResultsOf 118 patients only 48 were eligible for the analysis. RR, G, or TGII appear as significant prognostic factors, and, after multivariate analysis, a reduction rate of 20% the baseline or more was associated with good survival (HR 0.321; CIs 0.156–0.661) as well as a G > -0.4%/day (HR 2.114; CIs 1.034–4.321), whereas TGII >190 was not correlated with the outcome (HR 1.788; CIs 0.789–4.055).ConclusionsIn patients with mPDAC, after 8 weeks of first-line CHT, CA 19-9-related tumor reduction or growth rate appear as valuable prognostic factors.     

Prognostic significance of serum CA19-9 levels in resected pancreatic cancer

Twenty-eight patients with histologically proven pancreatic adenocarcinoma were investigated to evaluate the utility of serum CA19-9 levels as a prognostic indicator after pancreatic resection. Three patients were excluded from the study because their serum CA19-9 levels remained normal throughout the course of the disease. Of the remaining 25 patients, those with preoperative serum CA19-9 levels ≤200U/ml had a better prognosis than those with serum CA19-9 levels >200 U/ml; however, the difference between the two groups was not significant (P=0.13). Serum CA19-9 levels 30 days after pancreatic resection were normalized (≤37 U/ml) in 11 patients (group A), and the survival rate of this group was significantly higher than that of the group of patients with persistently elevated CA19-9 levels (>37 U/ml) (group B) (P<0.005). Other factors i.e., preoperative CA19-9 values, tumor size, lymph node metastasis, histology, and stage classification showed no significant differences between group A and group B. Univariate analysis of the findings for the 25 patients showed that the stage classification and postoperative CA19-9 levels were of prognostic significance for prolonged survival. Other factors, i.e., gender, age, histology, preoperative CA19-9 levels, location of the tumor, and mode of operation, had no significance as prognostic indicators. Multivariate analysis showed that postoperative CA19-9 level was the only significant independent predictor of poor survival. Postoperative serum CA19-9 level appears to be useful as a prognostic indicator after resection of pancreatic cancer.     

Carbohydrate antigen CA 19-9: value in pancreatic pathology

In order to determine the diagnostic usefulness of the dosage of carbohydrate antigen (CA 19-9) serum levels in pancreatic diseases, 38 patients with pancreatic lesions proved at laparotomy were studied. Pancreatic lesions were classified into two groups: a) group I: pancreatic adenocarcinoma (17 cases) b) group II: benign pancreatic diseases (21 cases). CA 19-9 serum levels were statistically higher in patients of the first group (p less than 0.001). All patients except one with CA 19-9 higher than 60 U/ml had pancreatic carcinoma. All patients except two with CA 19-9 less than 60 U/ml had a benign lesion. The sensitivity and specificity of CA 19-9 were 88 and 95 p. 100 respectively. These results show that CA 19-9 dosage is useful in distinguishing between benign and malign lesions of the pancreas.     

Tumor markers in pancreatic cancer. Sensitivity and specificity of CA 19-9

The tumor marker CA 19-9 is based on monoclonal antibody to colonic carcinoma cell lines. In this study, the utility of the tumor marker in the diagnosis of pancreatic carcinoma was evaluated. CA 19-9 is strongly expressed in most tissue specimens obtained from pancreatic carcinomas. However, this antigen is also found in normal pancreas and specimens from chronic pancreatitis. The CA 19-9 is released into the circulation, and was found at increased concentrations (greater than 37 U/ml) in 87% of the patients with pancreatic carcinoma n = 145, as compared with only 13% in the group of patients with benign diseases n = 1,081 and 29% of those with extrapancreatic malignancies n = 691 (P less than 0.0001). The preoperatively raised CA 19-9 concentration in patients with stage I pancreatic carcinoma decreases after curative resection of the carcinoma to values within the normal range. However, in no CA 19-9 estimation following palliative surgical intervention of stage III and IV patients or in cases of inoperable carcinomas was a serum concentration of less than 37 U/ml recorded. Accordingly, the median survival of stage I patients was 29 months, and of stage III, IV and patients with inoperable carcinomas 6 months only.     

Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping

BackgroundCarbohydrate antigen 19-9 (CA19-9) is currently the most widely used biomarker for pancreatic cancer. It is well-known that Lewis and Secretor status can affect CA19-9 biosynthesis. This study was performed to optimize CA19-9 in detecting pancreatic cancer using Lewis and Secretor dependent cut-off values.MethodsLewis and Secretor genotypes were determined by Sanger sequencing in a large cohort of subjects (578 cases with pancreatic cancer, 210 cases with benign pancreatic disease, 315 normal subjects). The effectiveness of CA19-9 for detecting pancreatic cancer using Lewis and Secretor group dependent cut-off values was evaluated.ResultsThe Lewis (-), Mixed, and Secretor (-) groups had low, medium, and high CA19-9 biosynthesis, respectively. In Lewis (-) pancreatic cancer (all stages), CA19-9 had a sensitivity of 48.6% and a specificity of 95.9% when 1.8 U/mL was used as the cut-off value. The sensitivity of CA19-9 in detecting all stages of pancreatic cancer improved from 80.1% to 88.0% and the negative predictive value increased from 81.2% to 87.1% without compromising other values when using group dependent cut-off values. The sensitivity of CA19-9 for the detection of stage I, II pancreatic cancer increased from 76.1% to 87.2%.ConclusionsThe value of CA19-9 in detecting pancreatic cancer was optimized by using group dependent cut-off values based on Lewis and Secretor genotypes. CA19-9 can be applied as an early detector of pancreatic cancer using group dependent cut-off values.     

How does liver dysfunction influence serum CA 19-9 in pancreatic cancer?

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.     

Monitoring of CA19-9 and SPan-1 can facilitate the earlier confirmation of progressing pancreatic cancer during chemotherapy

BackgroundMeasurement of objective response to chemotherapy using imaging modalities is sometimes difficult in pancreatic cancer (PC). We aimed to verify whether monitoring of serum tumor markers (TMs), namely carcinoembryonic antigen, CA19-9, DUPAN-2, SPan-1, can facilitate earlier confirmation of treatment failure.MethodsMonitoring of serum TMs and computed tomography were performed every 4 weeks until progression of disease in 90 patients with PC undergoing gemcitabine therapy. In Group A (January 2006–October 2007), we analyzed the fluctuation rates of TMs with high pretreatment positive rates, and defined the criteria of progressive disease under TM monitoring (TM-PD). In Group B (November 2007–October 2008), we calculated the time to progression (TTP) under this TM-PD criteria, which was compared with the TTP under the RECIST criteria.ResultsCA19-9 and SPan-1 had the highest pretreatment positive rates: 83% and 90%, respectively. In Group A (CA19-9, n = 38; SPan-1, n = 36), TM-PD criteria were defined as follows: fluctuation rates were ≥25% for a month or ≥10% for 2 consecutive months in CA19-9, and ≥10% for a month in SPan-1. In Group B (CA19-9, n = 18; SPan-1, n = 17), under these criteria, one-month earlier confirmation of treatment failure was feasible in 61% by CA19-9 and 59% by SPan-1. Furthermore, the combination could facilitate this determination in 72% (35/49), significantly better than CA19-9 alone (P = 0.004).ConclusionMonitoring of serum CA19-9 and SPan-1 is helpful for earlier confirmation of treatment failure during gemcitabine therapy in PC.     

Utility of serum CA 19-9 monitoring in preoperative radiotherapy for pancreatic cancer.

BACKGROUND/AIMS: Pancreatic cancer is extremely refractory even to aggressive treatments including surgery, resulting in early metastasis and/or local recurrence. We investigated changes in serum tumor marker CA 19-9 levels during preoperative radiotherapy in conjunction with initial treatment failure. METHODOLOGY: Twenty-three patients presenting with localized disease and an increased serum CA 19-9 level, who were slated to undergo pancreatectomy and/or intraoperative radiotherapy following preoperative radiotherapy were reviewed. CA 19-9 response, the ratio of post-radiotherapy level before laparotomy to pre-radiotherapy level, was analyzed in relation to disease-control time and survival. RESULTS: Eleven patients revealed metastasis at restaging or laparotomy; 12 patients (52%) completed aggressive treatments. Initial failure was identified at the liver (52%), peritoneum (52%), or local site (26%) with a median disease-control time of 91 days; 7 patients showed combined failure. All but 1 patient died of cancer with a median survival time of 264 days. CA 19-9 response (range: 0-1185%) did not correlate with disease-control time or survival; 8 progressive-disease patients (> 140% response), however, showed significantly shorter disease-control time than 15 nonprogressive-disease patients (< or = 140% response). CONCLUSIONS: CA 19-9 monitoring is useful in preoperative radiotherapy for identifying patients who will not benefit by succeeding aggressive treatments by predicting early metastasis.     

Comparative studies on expression of CA 19-9 and DU-PAN-2 in pancreatic cancer tissue

Thirty-eight human pancreatic cancer cases were examined by immunohistochemistry for expression of CA 19-9 and DU-PAN-2 antigens by the respective monoclonal antibodies. CA 19-9 was expressed in 82% and DU-PAN-2 in 87% of cases. A combination of two antibodies increased the reactivity to 97%. Six CA 19-9-negative cases were DU-PAN-2 positive and 4 DU-PAN-2-negative cases expressed CA 19-9. In only 1 case (an anaplastic carcinoma), neither of the antibodies was reactive with cancer cells. The reactivity of tumor cells with each of the antibodies varied from case to case, and, within the same tumor, from one area to another. Histologically, all but one tumor were adenocarcinomas. Thirty-five cases showed areas of either a moderate degree of differentiation (16 cases), poor differentiation (11 cases) or anaplastic areas (8 cases). Although both antigens were expressed in a greater number of cancer cells in well differentiated areas, and less frequently in poorly differentiated and anaplastic regions, the difference in antigen expression in relation to the degree of tumor differentiation was not statistically significant. The cellular localization of the antigens varied. DU-PAN-2 was primarily localized within the cytoplasm, whereas CA 19-9 was found mostly on the luminal cell surface and in luminal content of the glandular structure. In tumor-free pancreatic tissue, adjacent to the tumor, CA 19-9 was detected almost exclusively in the cells of large and medium sized ducts, whereas DU-PAN-2 was primarily expressed in terminal ductular and centrocinar cells. The results indicate that a cocktail of CA 19-9 and DU-PAN-2 antibodies could increase the likelihood of identifying a biomarker in most patients with pancreatic cancer.