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.     

Evaluation of CA19-9 serum levels for monitoring disease activity during chemotherapy of pancreatic adenocarcinoma

Summary Between 1987 and 1990 21 patients with proven adenocarcinoma of the pancreas were treated with chemotherapy in four different phase II studies. For 14 patients, serial measurements of CA19-9 serum levels and clinical evaluations of response by computed tomography scan and/or ultrasound were available. Clinical stable disease and progressive disease were accompanied by stable or exponentially rising serum levels of CA19-9. One patient with clinical partial remission showed a 90% decline of CA19-9. However, a 75% decline of CA19-9 was also observed in a patient with rapidly progressive disease. These data seem to indicate that the CA19-9 serum level may be used as an easy and sensitive tool to evaluate progressive disease during chemotherapy.     

Prognostic factors related with survival in patients with pancreatic adenocarcinoma

The prognosis in patients with pancreatic cancer is poor and this cancer is the fourth leading cause of cancer-related death worldwide. Although surgical resection is the only curative treatment of choice for pancreatic cancer, the majority of patients are diagnosed at an advanced stage, thus only 10%-15% of them are suitable for curative resection and the overall survival is less than 5%. Chemotherapy for metastatic disease is to palliate symptoms of patients and to improve survival. Therefore, prognostic factors are important and a correct definition of poor prognostic factors may help to guide more aggressive adjuvant or aggressive treatment protocols in patients with pancreatic cancer. This article reviews the prognostic factors affecting survival of patients with pancreatic cancer in the light of recent advances in the literature.     

Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study

BackgroundThe aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study.MethodsData were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index.ResultsCompared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069–1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032–1.736; p = 0.0277). High carbohydrate antigen 19–9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261–2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199–1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001).ConclusionsOur large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.     

CA19-9 level determines therapeutic modality in pancreatic cancer patients with para-aortic lymph node metastasis

Background: In general, para-aortic lymph node(LN16) metastasis has been considered as a contraindication for pancreatic resection. However, some pancreatic cancer patients with LN16 metastasis have been reported to survive for longer than expected after pancreatectomy. The purpose of this study was to determine whether pancreatic cancer patients with LN16 metastasis might benefit from surgery.Methods: We retrospectively reviewed 201 consecutive patients with invasive pancreatic ductal adenocarcinoma who underwent surgery at Osaka National Hospital between April 2003 and December 2012.These patients included 22 patients with LN16 metastasis who underwent an extended lymphadenectomy and 25 patients who underwent a palliative surgical biliary and gastric bypass. The clinicopathological data and outcomes were evaluated using univariate and multivariate analyses.Results: The overall survival of the patients with LN16 metastasis was poorer than that of the LN16-negative patients(P = 0.0014). An overall survival analysis of the LN16-positive patients stratified according to the preoperative CA19-9 level showed a significant difference between patients with a low preoperative CA19-9 level(≤360 U/mL) and those with a high preoperative CA19-9 level(360 U/mL)(P = 0.0301). No significant difference in overall survival of patients was observed between those with LN16 positivity and those who underwent bypass surgery. However, the overall survival of the LN16-positive patients with a CA19-9 level ≤360 U/mL(n = 11) was significantly higher than that of those who underwent bypass surgery(P = 0.0452).Conclusion: Surgical resection and extended lymphadenectomy remains an option for pancreatic cancer patients with LN16-positivity whose CA19-9 level is ≤360 U/mL.     

New observations on the utility of CA19-9 as a biomarker in Lewis negative patients with pancreatic cancer

Background

Carbohydrate antigen 19-9 (CA19-9) is the best-validated biomarker for pancreatic cancer. The National Comprehensive Cancer Network (NCCN) guideline asserts that “CA19-9 will be undetectable in Lewis antigen-negative individuals”. However, reports of CA19-9 secretion and its significance in Lewis (-) patients with pancreatic cancer have been inconsistent. This study was to examine serum CA19-9 levels in patients with pancreatic cancer according to Lewis status.

肿瘤标志物CA242与CA19-9对胰腺癌的诊断价值

目的:比较血清肿瘤标志物CA242与CA19-9对胰腺癌的诊断价值。方法:1996年4月至1997年6月,北京医院对门诊及住院197例患者进行了血清CA19-9的检测,148例进行了CA242的检测,其中25例为临床明确诊断为胰腺癌,12例为急性胰腺炎,18例为良性阻塞性黄疸。结果显示:胰腺癌患者血清CA19-9和CA242较对照明显增高,其中25例胰腺癌患者有21例CA19-9阳性,检测的灵敏度为84％,特异性为74.4％,有17例CA242阳性,检测的灵敏度为68％,特异性为87.8％。CA242与CA19-9比较,灵敏度无显著差异(0.10相似文献   

Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer

ObjectivesTo establish and evaluate a first generation patient-derived xenograft (PDX) model in nude mice using tumors resected from pancreatic cancer (PC) patients for the identification of key factors that influence xenograft success and prediction of patient prognosis.MethodsPrimary tumor samples harvested from PC patients who underwent curative resection between May 2016 and April 2018 at our hospital were xenografted into nude mice. Tumor size was evaluated for 2 months. Patients’ baseline characteristics and follow-up data were analyzed.ResultsTumor xenograft models were generated from 67 patients; 30 (44.8%) were successful and 37 (55.2%) failed. Xenograft models could recapitulate the pathology and genetic information of the primary tumors. Univariate analysis identified tumor engraftment, post-operation CA19-9, tumor size, lymph node status, and lymphovascular invasion as significant predictors (P=0.000, 0.023, 0.004, 0.035 and 0.005, respectively) of disease-free survival (DFS). Multivariate Cox regression analysis confirmed tumor engraftment, tumor size and lymphovascular invasion function as independent risk factors for DFS (P=0.000, 0.039 and 0.025, respectively). The hazard ratio of tumor engraftment for DFS was 0.239 (95% confidence interval, 0.109 to 0.524). Kaplan–Meier analysis of DFS indicated an unfavorable outcome in the engraftment group compared to that in the failed engraftment group (6.2 vs. 12.2 months, log rank P=0.000).ConclusionThe pathology and genetic information of primary PC tumors are recapitulated in the PDX tumor model in nude mice. Furthermore, engraftment success is an effective predictor of disease recurrence in patients after surgery.     

Evaluation of preoperative prognostic factors in patients with resectable pancreatic ductal adenocarcinoma

Abstract

Objective: Upfront surgery is the standard treatment for resectable pancreatic ductal adenocarcinomas (R-PDACs); however, these tumors often recur. We investigated the factors governing recurrence and prognosis in patients with R-PDAC.

Methods: We analyzed 359 patients who underwent upfront surgery for R-PDAC between 2000 and 2016, and evaluated the relationship between clinicopathological factors and recurrence/outcomes.

Results: The rate of recurrence was 74% while the median time to recurrence was 1.2 years. On multivariate analysis, carbohydrate antigen 19-9 (CA19-9) >37?U/mL (hazard ratio [HR]: 2.02), tumor size >2.6?cm (HR: 1.50), pathological grade 3 (HR: 2.58), lymph node metastasis (LNM; HR: 1.65), residual tumor (HR: 1.47) and forgoing adjuvant chemotherapy (HR: 1.31) were risk factors for a shorter recurrence-free survival; the median survival time (MST) was 2.8 years. On multivariate analysis, CA19-9?>?37?U/mL (HR: 1.99), tumor size >2.6?cm (HR: 1.43), pathological grade 3 (HR: 2.93), pathological portal vein invasion (HR: 1.48), LNM (HR: 1.79) and forgoing adjuvant chemotherapy (HR: 1.39) were risk factors for shorter disease-specific survival intervals. When examining outcomes according to preoperatively measurable factors (CA19-9?>?37?U/mL and tumor size >2.6?cm), the median time to recurrence and MSTs of patients with none (n?=?83), one (n?=?112) and both (n?=?164) risk factors were 3.2, 1.8 and 0.8 years; and 7.2, 4.0 and 1.7 years, respectively.

Conclusions: CA19-9?>?37?U/mL and tumor size >2.6?cm were preoperative independent risk factors for early recurrence and poor outcomes in patients with R-PDAC. Therefore, preoperative treatment should be considered for such patients.     

CA19-9在2型糖尿病与消化道恶性肿瘤患者中的阳性界值

目的 探讨鉴别2型糖尿病(T2DM)和消化道恶性肿瘤患者血清CA19-9的阳性界值.方法 化学发光法测定T2DM组(n=120)和消化道恶性肿瘤组(n=403)血清CA19-9浓度.统计软件SPSS17.0对各组进行组间对比分析,绘制ROC曲线确定CA19-9在2型糖尿病与消化道恶性肿瘤的阳性界值.结果 T2DM组和消化道恶性肿瘤组间CA19-9有显著性差异.ROC曲线确定CA19-9在两组间的阳性界值为40.0 U/ml.结论 以40.0 U/ml作为CA19-9阳性界值可以提高消化道恶性肿瘤诊断价值.     

Ca 19-9 serum course and prognosis of pancreatic cancer

Conclusion CA 19-9 measurement is a simple test that can be used for diagnosis as well as for prediction of resection, survival rate after surgery, and recurrences. Methods Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. Results The discriminating capacity between benign and malignant disease was high for CA 19-9, especially in patients with pancreatic cancer (n=347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. CA 19-9 levels were significantly lower in patients with resectable tumors (n=126) than in those with unresectable tumors (n=221,p<0.0001) (sensitivity 74 vs 90%). CA 19-9 dropped sharply after resection, but normalized only in 29, 13, and 10% in patients with stage I, II, and III, respectively. In unresectable tumors no significant decrease of CA 19-9 after laparotomy or bypass operation was found. In patients of the same tumor stage, the median survival time in those whose CA 19-9 levels returned to normal after resection was significantly longer than in those with postoperative CA 19-9 levels that decreased, but did not return to normal (in stage I, 33 vs 11.3 mo, in stage II, 41 vs 8.6 mo, and in stage III, 28 vs 10.8 mo). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels.     

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.     

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma: Primary tumors compared to sites of metastasis

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with poor survival. The dense desmoplastic stroma in PDAC contributes to treatment resistance. Among the components comprising the tumor stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci of PDAC. However, the effects of treatment and location of HA expression as a biomarker signature remain unknown; this study sought to compare HA expression in primary and metastatic sites of PDAC.MethodsTissue from primary and metastatic PDACs were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained for H&E, HA, and CD44. Associations between HA levels and the evaluated variables were examined including progression free survival and overall survival.ResultsHA score was significantly higher in primary PDACs compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastases compared to metastases at other sites (p = 0.0478). In the treatment-naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively).ConclusionsHA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.     

Microbiome and pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) incidence and related-deaths are increasing worldwide. PDAC is characterized by poor prognosis due to late diagnosis, high metastatic capacity and resistance to therapy. This is partially due to its specific microenvironment, where the stroma is prominent over tumor cells. Besides the oral and gut microbiota, the intratumor microbiome, i.e. the bacterial and fungal microorganisms present within the tumor, was recently introduced as a new partner of the tumor microenvironment of PDAC modulating pancreatic carcinogenesis, intratumor immune infiltrates, and response to chemotherapy. In this review, we propose an overview of current knowledge about the roles of bacteria and fungi in PDAC development and biology, and discuss potential therapeutic implications.     

S-1 plus gemcitabine chemotherapy followed by concurrent radiotherapy and maintenance therapy with S-1 for unresectable pancreatic cancer

AIM: To investigate the feasibility and efficacy of the combination of S-1 with gemcitabine followed by oral S-1 with concurrent radiotherapy (intensity modulated radiotherapy, IMRT) and maintenance therapy with S-1 for locally advanced pancreatic cancer.METHODS: Subjects selected in the study were patients who had unresectable and locally advanced pancreatic cancer without distant metastases, adequate organ and marrow functions, an Eastern Cooperative Oncology Group performance status of 0-1 and no prior anticancer therapy. Initially the subjects received two cycles of chemotherapy, oral administration of S-1 40 mg/m² twice daily from day 1 to day 14 of a 21-d cycle, with 30-min intravenous infusions of gemcitabine 1000 mg/m² on day 1 and day 8. Two weeks after the completion of chemotherapy, S-1 was administered orally with concurrent IMRT. Oral S-1 was administered at a dose of 80 mg/m² per day twice daily from day 1 to day 14 and from day 22 to day 35. Radiation was concurrently delivered at a dose of 50.4 Gy (1.8 Gy/d, 5 times per week, 28 fractions). One month after the completion of chemotherapy and radiotherapy, S-1 was administered orally at a dose of 80 mg/m² per day twice daily for 14 d, followed by a 14-d rest period. This cycle was repeated as maintenance therapy, until unacceptable toxicity occurred or the disease worsened. Thirty-two patients were involved in this study. The median follow-up was 15.6 mo (range: 8.6-32.3 mo).RESULTS: Thirty-two patients completed the scheduled course of chemotherapy, while 30 patients (93.8%) received chemoradiotherapy with two patients ceasing to continue with radiotherapy. The major toxic effects were nausea and leukopenia. There was no grade 4 toxicity or treatment-related death. According to the Response Evaluation Criteria in Solid Tumors criteria, the objective tumor response was partial response in 17 (53.1%) patients, stable disease in 9 (28.1%), and progressive disease in 6 (18.8%). The median overall survival and median progression-free survival were 15.2 mo and 9.3 mo, respectively. The survival rates at 1 year and 2 years were 75% and 34.4%, respectively.CONCLUSION: The combination of S-1 with gemcitabine followed by oral S-1 with IMRT and maintenance therapy with S-1 alone in patients with locally advanced pancreatic cancer may be considered a well-tolerated, promising treatment regimen.     

Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study

BackgroundCarcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30–60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC.MethodsWe conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed.ResultsMedian overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p < 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45–2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71–1.40).ConclusionsThe present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.     

Autoimmune pancreatitis associated with a large pancreatic pseudocyst

INTRODUCTIONAutoimmune pancreatitis (AIP) is a benign disease that responds well to steroid treatment. Characteristics in-clude radiological evidence of an irregular narrowing of the pancreatic main duct and a diffuse enlargement of the pancreas, together…     

Efficacy and tolerance of gemcitabine and nab-paclitaxel in elderly patients with advanced pancreatic ductal adenocarcinoma

BackgroundThe efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting.Patients and methodsWe retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years.ResultsThe study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8–10.2) and PFS (median, 5.5 months; 95% CI, 4.8–6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis.ConclusionGnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.     

Novel serum tumor marker, RCASl, in pancreatic diseases

AIM: As tumor markers for pancreatic carcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been used, but the sensitivity and specificity are not enough for the diagnosis of pancreatic carcinoma. METHODS: A novel serum tumor marker, RCAS1, was compared with two conventional serum tumor markers, CEA (highly specific for pancreatic cancer) and CA 19-9 (highly sensitive for pancreatic cancer), in 48 patients with pancreatic exocrine tumors. RESULTS: When the diagnosis of benign or malignant conditions was examined by one tumor marker, the sensitivity of RCAS1 alone (55%) was higher than that of CEA alone (27%) and the specificity of RCAS1 alone (92%) was greater than that of CA19-9 alone (78%). When examined by a combination of two markers, the sensitivity of a combination of RCAS1 and CA19-9 (95%) was superior to those of CA19-9 alone (78%), RCAS1 alone (55%, P = 0.002), CEA alone (27%) (P<0.001), RCAS1 and CEA (59%) and CA19-9 and CEA (82%). CONCLUSION: These results suggest that the combination of RCAS1 and CA19-9 is highly sensitive for pancreatic carcinoma.