Combination of CA19-9 and Blood Free-Circulating Methylated RUNX3 May Be Useful to Diagnose Stage I Pancreatic Cancer

Oncology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Yuko Fujimoto ◽  
Yutaka Suehiro ◽  
Seiji Kaino ◽  
Shigeyuki Suenaga ◽  
Takanori Tsuyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Pancreatic Disease ◽  
Carbohydrate Antigen ◽  
Screening Strategy ◽  
Response To Therapy ◽  
Stage I ◽  
Bisulfite Treatment ◽  
Sample Amount

<b><i>Background:</i></b> Although serum carbohydrate antigen 19-9 (CA19-9) is widely used as a useful biomarker of pancreatic cancer for monitoring the response to therapy, it is not recommended for screening of early pancreatic cancer because of its limited sensitivity for small tumors. Thus, it is critical to discover novel serum biomarkers to complement CA19-9 in order to improve sensitivity. Although methylated runt-related transcription factor 3 (<i>RUNX3</i>) is a biomarker of pancreatic cancer, its detection by conventional bisulfite-based methylation assays from a small serum sample amount is very difficult. Therefore, we developed a new methylation assay, the combined restriction digital PCR (CORD) assay, that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. <b><i>Objectives:</i></b> We evaluated the sensitivity and specificity of serum DNA testing of methylated <i>RUNX3</i> by the CORD assay in combination with and without CA19-9 for the detection of pancreatic cancer in 55 patients with pancreatic cancer, 12 patients with benign pancreatic disease, and 80 healthy individuals. <b><i>Results:</i></b> The CORD assay of methylated <i>RUNX3</i> had a sensitivity of 50.9% (28/55) and specificity of 93.5% (86/92). Combination of the CORD assay of methylated <i>RUNX3</i> and CA19-9 resulted in a sensitivity of 85.5% (47/55) and specificity of 93.5% (86/92) for all stages of pancreatic cancer and a sensitivity of 77.8% (7/9) for stage I pancreatic cancer. <b><i>Conclusions:</i></b> ombination of the CORD assay and CA19-9 may provide an alternative screening strategy for detecting early-stage pancreatic cancer.

scholarly journals Detection of KRAS Mutations in Circulating Tumor DNA by Digital PCR in Early Stages of Pancreatic Cancer

2016 ◽  
Vol 62 (11) ◽  
pp. 1482-1491 ◽  
Author(s):  
Nora Brychta ◽  
Thomas Krahn ◽  
Oliver von Ahsen
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Surgical Removal ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Detection Rates ◽  
Early Stages ◽  
Tumor Dna

Abstract BACKGROUND Since surgical removal remains the only cure for pancreatic cancer, early detection is of utmost importance. Circulating biomarkers have potential as diagnostic tool for pancreatic cancer, which typically causes clinical symptoms only in advanced stage. Because of their high prevalence in pancreatic cancer, KRAS proto-oncogene, GTPase [KRAS (previous name: Kirsten rat sarcoma viral oncogene homolog)] mutations may be used to identify tumor-derived circulating plasma DNA. Here we tested the diagnostic sensitivity of chip based digital PCR for the detection of KRAS mutations in circulating tumor DNA (ctDNA) in early stage pancreatic cancer. METHODS We analyzed matched plasma (2 mL) and tumor samples from 50 patients with pancreatic cancer. Early stages (I and II) were predominant (41/50) in this cohort. DNA was extracted from tumor and plasma samples and tested for the common codon 12 mutations G12D, G12V, and G12C by chip-based digital PCR. RESULTS We identified KRAS mutations in 72% of the tumors. 44% of the tumors were positive for G12D, 20% for G12V, and 10% for G12C. One tumor was positive for G12D and G12V. Analysis of the mutations in matched plasma samples revealed detection rates of 36% for G12D, 50% for G12V, and 0% for G12C. The detection appeared to be correlated with total number of tumor cells in the primary tumor. No KRAS mutations were detected in 20 samples of healthy control plasma. CONCLUSIONS Our results support further evaluation of tumor specific mutations as early diagnostic biomarkers using plasma samples as liquid biopsy.

Combination Chemotherapy (CVP or Chop)-Radiotherapy Approach in Early Stage Non-Hodgkin's Lymphomas

1982 ◽  
Vol 68 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Pasquale Comella ◽  
Gianfranco Scoppa ◽  
Giuseppe Abate ◽  
Giuseppe Comella ◽  
Gaetano Apice ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Early Stage ◽  
Response To Therapy ◽  
Stage I ◽  
Stage Ii ◽  
Actuarial Survival ◽  
Favorable Histology ◽  
Significant Difference ◽  
Extended Field ◽  
Hodgkin's Lymphomas

From January 1978 to December 1980, 42 patients with early stage non-Hodgkin's lymphoma other than of the gastrointestinal tract were treated with radiotherapy and combination chemotherapy. Eighteen patients in stage I were submitted to locally extended-field radiotherapy up to a mean dose of 48 Gy with a Co60 source and, after a 3-week rest period, to 6 cycles of combination chemotherapy. Twenty-four patients in stage II received 3 cycles of combination chemotherapy before and after irradiation, the same as for stage I. Combination chemotherapy consisted of cyclophosphamide, vincristine and prednisone (CVP) for 15 cases with favorable histology (3 NWDL, 1 NPDI, 11 DWDL), whereas it included cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) for 27 cases with unfavorable histology (20 DPDL, 3 DM, 4 DH). Complete remission (CR) was achieved in 35/42 (83%) patients, with a highly significant difference between stage I (100%) and stage II (71%). After 42 months of follow-up, the probability of survival for all patients was 72%. Survival was better for stage I (88%) than for stage II (68%) and for favorable histology (87%) as compared to unfavorable histology (70%). Furthermore, survival was highly influenced by response to therapy. Indeed, actuarial survival rate for CR was 91% as compared to a median survival time of 10.2 months for the remaining patients. Four patients, all with poor histology, relapsed after 5–24 (mean 11) months of CR. Only one of them had an extension in extranodal sites and eventually died, despite the salvage treatment utilized. In our experience, locally extended-field irradiation combined with chemotherapy gave a high proportion of CR and seemed to prevent relapses, particularly in extranodal sites.

An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15052-e15052
Author(s):  
Bradley D. McDowell ◽  
Brian J. Smith ◽  
Anna M Button ◽  
James R. Howe ◽  
Elizabeth A. Chrischilles ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Early Stage ◽  
Stage I ◽  
Stage Ii ◽  
Survival Times ◽  
Resection Rate ◽  
Selection Factors ◽  
The Impact

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p<0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]

scholarly journals Meta-analysis of the diagnostic performance of circulating microRNAs for pancreatic cancer

2020 ◽  
Author(s):  
Cheng Peng ◽  
Zhiqiang Li ◽  
Lihua Huang ◽  
Wenzhe Gao ◽  
Jiale Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Diagnostic Accuracy ◽  
Diagnostic Performance ◽  
Early Stage ◽  
Meta Analysis ◽  
Carbohydrate Antigen ◽  
Cochrane Library ◽  
Circulating Mirnas ◽  
China National Knowledge Infrastructure ◽  
Circulating Micrornas

Abstract Background: Pancreatic cancer (PC) is characterized by high malignancy and a poor prognosis. The detection of circulating microRNAs (miRNAs) is a liquid biopsy diagnostic approaches. Numerous studies have suggested that some differentially expressed miRNAs may be promising diagnostic markers for PC, but the results have varied among studies. The present study was performed to summarize the diagnostic accuracy of circulating miRNAs, carbohydrate antigen 19-9 (CA19-9), and the combination of miRNAs and CA19-9.Methods: A literature search of online databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang was conducted. Relative data were extracted from eligible included studies, and a meta-analysis was performed.Results: A total of 46 studies involving 4,326 PC patients and 4,277 non-PC controls were included. The pooled sensitivity (SEN), specificity (SPE) and AUC of the circulating miRNAs for differentiating PC patients from non-PC controls were 0.79 (0.77-0.81), 0.77 (0.75-0.79), and 0.85 (0.81-0.87), respectively. For CA19-9, the SEN, SPE and AUC were 0.78 (0.75-0.80), 0.90 (0.85-0.94) and 0.85 (0.82-0.88), respectively. The combination of miRNAs and CA19-9 greatly improved the SEN, SPE and AUC to 0.84 (0.80-0.87), 0.91 (0.89-0.93) and 0.94 (0.92-0.96), respectively. Moreover, circulating miRNAs also yielded an acceptable diagnostic accuracy for early-stage PC with a SEN of 0.79 (0.76-0.82), a SPE of 0.74 (0.68-0.79) and an AUC of 0.81 (0.77-0.84).Conclusions: Circulating miRNAs exhibited satisfactory diagnostic performance for PC and even early-stage PC. The combination of circulating miRNAs and the traditional marker CA19-9 can further improve the diagnostic accuracy, providing a novel strategy for PC diagnosis.

Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 349-349
Author(s):  
Heather Stuart ◽  
Caroline Ripat ◽  
Basem Azab ◽  
Danny Yakoub ◽  
Dido Franceschi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Clinical Stage ◽  
Stage I ◽  
Clinical Staging ◽  
Early Stage Disease ◽  
Risk Of Mortality ◽  
Stage Disease ◽  
Pathologic Staging ◽  
Group 2

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p < 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p < 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p < 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

scholarly journals The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice

Science ◽  
2019 ◽  
Vol 364 (6446) ◽  
pp. 1156-1162 ◽  
Author(s):  
Dannielle D. Engle ◽  
Hervé Tiriac ◽  
Keith D. Rivera ◽  
Arnaud Pommier ◽  
Sean Whalen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Pancreatic Disease ◽  
Carbohydrate Antigen ◽  
Matricellular Protein ◽  
Egfr Signaling ◽  
Sialyl Lewis ◽  
Egfr Ligands ◽  
Epidermal Growth

Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 and β1,3-galactosyltransferase 5 in mice, reconstituting the glycan sialyl-Lewisa, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricellular protein fibulin-3 increased its interaction with EGFR, and blockade of fibulin-3, EGFR ligands, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9–mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the KrasG12D oncogene to produce aggressive pancreatic cancer. These findings implicate CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominate CA19-9 as a therapeutic target.

scholarly journals O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2469 ◽  
Author(s):  
Takahiro Yokose ◽  
Yasuaki Kabe ◽  
Atsushi Matsuda ◽  
Minoru Kitago ◽  
Sachiko Matsuda ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Vesicles ◽  
Early Stage ◽  
Absolute Quantification ◽  
Serum Marker ◽  
Carbohydrate Antigen ◽  
Liquid Biopsies ◽  
Lectin Microarray ◽  
High Area ◽  
Quantitative Analyses

Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

Survival outcomes for various treatment modalities in early-stage grade 3 follicular lymphoma (FL3): a National Cancer Database (NCDB) study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7551-7551
Author(s):  
Upama Giri ◽  
Eric Vick ◽  
Sophia SeoHyeon Lee ◽  
Alaa Altahan ◽  
Noam Avraham VanderWalde ◽  
...  
Keyword(s):  
Cox Regression ◽  
Early Stage ◽  
Single Agent ◽  
Treatment Strategies ◽  
Small Sample ◽  
Response To Therapy ◽  
Stage I ◽  
Treatment Modalities ◽  
Rank Test ◽  
Multi Agent

7551 Background: The prognosis, response to therapy and curability of FL3 is controversial. 5-year Overall Survival (OS) in the literature ranges from 35-72% (Ganti 2006). The aim of this study was to compare the OS for patients with early-stage FL3 managed with single- and multi-agent chemotherapy (CT) with and without radiotherapy (RT). Methods: We identified patients (pts) diagnosed with stage I & II FL3 between 2004 – 2012 from the NCDB and categorized into 3 groups based on therapy – pts given single agent CT with or without RT were combined due to small sample sizes (SA±RT), multi-agent CT without RT (MA-RT), and multi-agent CT with RT (MA+RT). We calculated OS for each group using Kaplan-Meier method and compared the results using Log Rank test. Cox regression model was used to identify factors which had significant impact on OS. Results: 1,563 pts were identified – 827 (53%) with stage I and 736 (47%) with stage II FL3. Median age was 61 yrs (range 18-90yrs); 750 (48%) males, 813 (52%) females; 1423 (91%) whites, 76 (5%) blacks. 112 (7%) received SA±RT, 886 (57%) MA-RT and 565 (37%) MA+RT. 5-year OS for MA+RT (95%) was significantly more than MA-RT (87%; HR 0.33, P<0.001) or SA±RT (88%; HR 0.38, P=0.007). Cox regression indicated that age (HR 1.05, P<0.001), sex (HR 0.66 for females, P=0.02), comorbidities (HR 1.60 for Charlson Deyo Score 1, P=0.04; HR 3.07 for Score 2, P=0.001), stage (HR 1.79, P=0.001), insurance status (HR 0.22 for insured, P<0.001) and increasing year of diagnosis (HR 0.92, P=0.03) also had significant impact on OS. Median radiation dose for the MA+RT was 36Gy (interquartile range 30.6 – 36Gy), and the proportion of patients who received greater than 36Gy decreased from 55% in 2004 to 38% in 2012 and at the same time, the proportion of patients who received intensity modulated RT increased from 5% in 2004 to 15% in 2012. Use of MA CT declined (2004 95% v 2012 89%, P=0.02) but there was no significant trend in use of RT (2004 39% v 2012 34%) during the periods studied. Conclusions: For pts with early-stage FL3, there was an association of improved survival with the use of MA+RT over other treatment strategies and appear to have outcomes superior to what has been previously reported.

Preoperative Chemotherapy for Pancreatic Cancer Improves Survival and R0 Rate Even in Early Stage I

2020 ◽  
Vol 24 (10) ◽  
pp. 2409-2415 ◽  
Author(s):  
Eduardo A. Vega ◽  
Onur C. Kutlu ◽  
Omid Salehi ◽  
Daria James ◽  
Sylvia V. Alarcon ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Preoperative Chemotherapy ◽  
Early Stage ◽  
Stage I
Sign in / Sign up

Export Citation Format

Share Document