Association of RecQ1 A159C polymorphism with overall survival of patients with resected pancreatic cancer: A replication study in RTOG 9704.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 156-156 ◽  
Author(s):  
D. Li ◽  
J. Moughan ◽  
C. H. Crane ◽  
J. P. Hoffman ◽  
W. Regine ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Surgical Margin ◽  
Cox Proportional Hazards Model ◽  
Tumor Diameter ◽  
Genotype Distribution ◽  
Resectable Pancreatic Cancer ◽  
Dna Repair Gene ◽  
Significant Difference

156 Background: To confirm whether a previously observed association between a DNA repair gene and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population. Methods: We evaluated the RecQ1 A159C variant (rs13035) in patients with resected pancreatic cancer who were enrolled on the RTOG 9704 trial of 5FU-based chemoradiation preceded and followed by 5-FU or gemcitabine. DNA was extracted from paraffin-embedded tissue sections and genotype was determined using the Taqman method. A multivariate Cox proportional hazards model was used to determine if there is a correlation between genotype and overall survival (OS). Models were built using the stepwise selection procedure. The following variables were included in the model: genotype, treatment arm, age, gender, race, nodal involvement, tumor diameter, and surgical margin status. Results: A total of 154 out of 451 eligible patients were evaluated for the RecQ1genotype. There was no significant difference in baseline characteristics and overall survival time between patients who were and were not evaluated for the RecQ1genotype. In the 154 evaluated patients, the genotype distribution followed the Hardy-Weinberg Equilibrium, i.e. 37% had genotype AA, 43% AC, and 20% CC. The RecQ1 variant AC/CC genotype carriers were more likely to be node positive compared to the AA carrier (p=0.03). The median survival times (95% C.I.) for AA, AC, and CC carriers were 1.72 (1.36, 2.17), 1.57 (1.18, 1.80), and 1.18 (0.86, 1.75) years, respectively. On multivariate analysis, patients with the AC/CC genotypes were more likely to die than patients with AA genotype (HR=1.54, 95% C.I. = [1.07, 2.23], p=0.022). This effect is more definitive for patients on the 5-FU arm (n=82) (HR=1.64, 95% C.I. = [0.99, 2.70], p=0.055) than for patients on the gemcitabine arm (n=72, HR=1.46, 95% C.I. = [0.81, 2.63], p=0.21). Conclusions: Results of this study suggest that the RecQ1 A159C genotype is a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant chemoradiation. No significant financial relationships to disclose.

Overall survival with preoperative biliary drainage in patients with resectable pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 314-314
Author(s):  
Tobin Joel Crill Strom ◽  
Sarah E. Hoffe ◽  
Shivakumar Vignesh ◽  
Jason Klapman ◽  
Cynthia L. Harris ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Size ◽  
Biliary Drainage ◽  
Cox Regression ◽  
Neoadjuvant Treatment ◽  
Preoperative Biliary Drainage ◽  
Resectable Pancreatic Cancer ◽  
Pathologic Features

314 Background: Resectable pancreatic cancer patients often present with obstructive jaundice necessitating the placement of biliary stents or percutaneouse drainage catheters. We sought to evaluate whether preoperative biliary drainage affects recurrence and survival. Methods: An IRB-approved study was conducted on our institutional tumor registry to identify pancreatic cancer patients who were treated with upfront surgery between 2000 and 2012. Patients were then stratified by preoperative use of endoscopically placed stents (ERCP), percutaneous catheters (PTC), or no biliary drainage (NBD). The primary endpoint was overall survival (OS). Survival curves were calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis (MVA) was performed with a Cox regression model. Results: We identified 202 patients for the study (21 PTC; 89 ERCP; 92 NBD). Key differences between the 3 groups were mean pathologic tumor size (p=0.005), pathologic T3/4 (p =0.01), and pathologic N1 (p=0.007) status, with more aggressive pathologic features in PTC patients. PTC patients had a non-significant increase in rate of hepatic recurrences compared with ERCP and NBD patients (47.4% vs. 26.6% vs. 28.7%, respectively; p=0.20). PTC patients also had worse median and 3 year survival (21 months and 16%) compared to ERCP (23.3 months and 39%) and NBD patients (29 months and 45%, p=0.02). MVA revealed that PTC was an independent predictor of worse overall survival (HR 2.3[95% CI 1.3-4.0], p=0.005), along with pathologic tumor size (HR 1.1[1.0-1.3], p=0.008), nodes positive (HR 1.1[1.1-1.2], p=0.001), and post-operative CA19-9 >90 (HR 2.6[1.5-4.4], p=0.001). Conclusions: Patients with resectable pancreatic cancer who require a pre-operative PTC drain had a non-significant increase in hepatic recurrence rate and worse overall survival than patients who either had an ERCP stent placed or no biliary decompression prior to surgery. Given their worse prognosis, patients who require PTC placement might also benefit from neoadjuvant treatment with restaging prior to surgery.

Association of decline in serum Ca19-9 after neoadjuvant therapy with improved survival among borderline resectable pancreatic cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15082-e15082 ◽  
Author(s):  
Susan Tsai ◽  
Anna Mahmoud ◽  
Ben George ◽  
Tracy R. Kelly ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Response To Therapy ◽  
Proportional Hazard ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Cox Proportional Hazard ◽  
Localized Disease

e15082 Background: Serum Ca19-9 (19-9) decline in response to therapy has been associated with an increased overall survival in metastatic pancreatic cancer patients (pts). However, the prognostic value of a 19-9 decline after neoadjuvant therapy in pts with localized disease is less well defined. Methods: We evaluated 73 pts with NCCN defined BRPC who received neoadjuvant therapy with induction chemotherapy (CRX) followed by chemoradiation (CRT). Staging with CT and 19-9 was obtained at three defined time points: baseline (bilirubin normal), after CRX, and following CRT (pre-surgical). Change in 19-9 (δ19-9) was defined as: (baseline 19-9- pre-surgical 19-9)/baseline 19-9. δ19-9 was classified as: absent (δ19-9<0) or minimal (0 <δ19-9<0.25), low (0.25<δ19-9<0.50), moderate (0.50<δ19-9<0.75), high (δ19-9> 0.75). Results: Of the 73 pts, 20 pts had normal/undetectable 19-9 and were excluded from the analysis. Of the remaining 53 pts, mean 19-9 levels at baseline, after CRX, and after CRT were 956, 164, and 139 U/mL, respectively. The mean change in 19-9 after CRX was 44%. Changes in 19-9 after CRX correlated with continued decline in 19-9 after CRT (Spearman rho = 0.81, p<0.001). δ19-9 was high in 38 (71%), moderate in 9 (17%), min/low in 1 (2%), and absent in 5 (9%). Of the 53 pts, 49 (92%) were considered for surgery after neoadjuvant therapy and 38 (72%) underwent pancreatectomy. In a multivariate logistic regression, higher δ19-9 was associated with a 5.4 fold increased odds of completing all neoadjuvant therapy including surgery as compared to pts with no change in 19-9 (absent δ19-9; HR 5.4, p=0.12). Patients with absent δ19-9 had a worse overall survival than pts with minimal to high δ19-9 (median survival 11.5 mo vs. 30.1 mo, p = 0.0002). In a multivariate Cox proportional hazard, a decline in pre-surgical 19-9 from baseline was associated with improved survival (HR 0.21, p =0.02). Conclusions: Following neoadjuvant therapy, a decline in 19-9 is associated with surgical resection and improved overall survival. An increase in 19-9 above baseline (the absent δ19-9 group) prior to surgery is a poor prognostic marker and such patients may benefit from additional systemic therapy.

scholarly journals A268 PREOPERATIVE EUS-GUIDED FNA IS ASSOCIATED WITH BETTER OVERALL SURVIVAL IN RESECTABLE PANCREATIC CANCER WHEN COMPARED TO UPFRONT SURGERY WITHOUT PREOPERATIVE TISSUE ACQUISITION: A SYSTEMIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 145-146
Author(s):  
A Alghamdi ◽  
V Palmieri ◽  
N Alotaibi ◽  
M Martel ◽  
A N Barkun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Tumor Recurrence ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Systemic Review ◽  
Resectable Pancreatic Cancer ◽  
Tumor Seeding ◽  
Free Survival ◽  
Significant Difference

Abstract Background Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the standard of care in advanced pancreatic cancer. In resectable disease, preoperative EUS-FNA can help to identify benign etiology and other cancers while preventing unnecessary surgery. However, concerns regarding tumor seeding and pancreatitis have led some experts to advocate for upfront surgery without tissue sampling. Aims To conduct a systematic review and meta-analysis of the risks and benefits of performing pre-operative EUS-FNA in patients with suspected, resectable pancreatic cancer. Methods A literature search was performed up to April 2019 using MEDLINE, EMBASE, and ISI Web of Knowledge databases with terms specified for pancreatic neoplasm and FNA. All fully published adult studies that compared preoperative EUS-FNA to EUS without FNA in resectable pancreatic cancer for short- and long-term outcomes were included. Results were reported as Odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (CI) using a random effects model. Heterogeneity, publication bias and quality of studies were evaluated. Sensitivity analyses were performed. The primary outcome is overall survival. Secondary outcomes include cancer free survival, tumor recurrence and seeding, and post FNA adverse events. Results An initial search yielded 2814 citations. Six retrospective studies were included with 1155 patients in the EUS-FNA group vs 2067 patients in the comparator group. Overall survival was reported in three studies (n=2701: 796 EUS-FNA, 1905 non-FNA). Patients with preoperative EUS-FNA had better overall survival compared to the non-FNA group (WMD, 4.40 months [0.02 to 8.78]). In adenocarcinoma patients (2 studies, n=2050), there was no significant difference in overall survival (WMD, 2.94 months [-3.87 to 9.74]). Cancer-free survival did not differ significantly between the two groups (WMD, 2.08 months [-2.22 to 6.38]). Moreover, EUS with FNA was not associated with increased rates of tumor recurrence (OR, 0.55 [0.30–1.02]) or peritoneal carcinomatosis (OR, 0.81 [0.56–1.18]). Post-FNA pancreatitis was rare (1.7%), with all patients treated conservatively. Sensitivity analyses yielded similar findings across the different outcomes tested. Conclusions In this meta-analysis, preoperative EUS-FNA in resectable pancreatic cancer was associated with significantly greater overall survival when compared to the non-FNA group with no significant difference in rate of tumour recurrence and/or peritoneal seeding. These findings are limited by the retrospective nature of the included studies; randomized controlled trials are needed to confirm these results. Funding Agencies None

Symptomatic and Incidental Thromboses Are Both Associated with Mortality In Pancreatic Cancer

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3167-3167 ◽  
Author(s):  
Laurel A. Menapace ◽  
Derick R. Peterson ◽  
Andrea Berry ◽  
Tarek Sousou ◽  
Alok A. Khorana
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Median Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Conflicts Of Interest ◽  
Significant Proportion ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference

Abstract Abstract 3167 Background: Incidentally diagnosed venous thromboembolism (VTE) is a growing clinical problem. Although pancreatic cancer is well-known to be associated with VTE, contemporary rates of incidental and symptomatic VTE events and their association with mortality are incompletely understood. Methods: We conducted a retrospective cohort study of consecutive pancreatic adenocarcinoma patients seen at the University of Rochester from 2006–2009. Radiologic reports were reviewed for presence of pulmonary embolism (PE), deep venous thrombosis (DVT), and visceral vein thrombosis. Multiple clinical variables and mortality outcomes were collected. Data were analyzed using a multivariate Cox proportional hazards model. Results: A total of 1151 radiologic exams for 135 patients were included. Forty-seven patients (34.8%) experienced at least one VTE event. There were 12 PEs (n=12 patients, 8.9%), 34 DVTs (n=17 patients, 12.6%), 47 visceral vein (n=31 patients, 22.9%) and 2 arterial (n=2 patients, 1.5%) events. Twenty-one patients (15.5%) experienced more than one event. Incidental events comprised 33.3% (n=4) of PEs, 17.6% (n=6) of DVTs and 100% (n=47) of visceral VTE. Median survival for the study population was 237 (95% CI 199–277) days. Patients with VTE had significantly reduced survival (73 vs. 233 days at 3 months post-diagnosis; 66 vs. 245 days at 6 months post-diagnosis). There was no significant difference between asymptomatic and symptomatic events in terms of conditional median survival at 3 months-, 6 months- or 1 year-post diagnosis. In multivariate analysis, occurrence of either DVT (HR 7.4 95% CI 3.8–14.6, P<0.0001) or visceral asymptomatic events (HR 2.5 95% CI 1.6–3.8, P=0.0001) was significantly associated with mortality along with advanced stage. Conclusions: VTE occurs in over one-third of pancreatic cancer patients, including a significant proportion with incidentally discovered events. Patients with visceral vein events are generally not anticoagulated but these findings suggest a similar association with mortality as symptomatic DVT. Our findings require reconsideration of prognosis and anticoagulation options in pancreatic cancer patients with both incidental and symptomatic VTE. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer

2008 ◽  
Vol 26 (25) ◽  
pp. 4072-4077 ◽  
Author(s):  
Jennifer K. Litton ◽  
Ana M. Gonzalez-Angulo ◽  
Carla L. Warneke ◽  
Aman U. Buzdar ◽  
Shu-Wan Kau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathologic Complete Response ◽  
Operable Breast Cancer ◽  
Obese Patients ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Response To Neoadjuvant Chemotherapy

Purpose To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. Patients and Methods From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI of 25 to < 30 kg/m2), or normal/underweight (BMI < 25 kg/m2). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer–specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. Results Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. Conclusion Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

scholarly journals A 25-gene classifier predicts overall survival in resectable pancreatic cancer

BMC Medicine ◽  
2017 ◽  
Vol 15 (1) ◽  
Author(s):  
David J. Birnbaum ◽  
Pascal Finetti ◽  
Alexia Lopresti ◽  
Marine Gilabert ◽  
Flora Poizat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Resectable Pancreatic Cancer

scholarly journals Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multi-centre, parallel group, double-blind, randomised controlled clinical trial (MISTRAL)

2020 ◽  
Author(s):  
Kathrin Wode ◽  
Johanna Hök Nordberg ◽  
Gunver Sophia Kienle ◽  
Nils Elander ◽  
Britt-Marie Bernhardson ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Health Related Quality ◽  
Mistletoe Extract ◽  
Related Quality ◽  
Health Related

Abstract Background Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard 18 treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with 19 regard to overall survival and health-related quality of life. Methods The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01mg to 20mg three times per week for nine months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status zero to two; main exclusion criteria are life expectancy less than four weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews. Discussion To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer. Trial registration EU Clinical Trial Register, EudraCT Number 2014-004552-64. Registered 19 January 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004552-64/SE

scholarly journals Immunological predictors of overall survival in treatment naïve metastatic pancreatic cancer patients

2015 ◽  
Vol 3 (S2) ◽  
Author(s):  
Matthew R Farren ◽  
Thomas Mace ◽  
Susan Geyer ◽  
Sameh Mikhail ◽  
Christina Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Metastatic Pancreatic Cancer ◽  
Treatment Naïve

scholarly journals RAD51 is a potential marker for prognosis and regulates cell proliferation in pancreatic cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaomeng Zhang ◽  
Ningyi Ma ◽  
Weiqiang Yao ◽  
Shuo Li ◽  
Zhigang Ren
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Aerobic Glycolysis ◽  
Cell Counting ◽  
Survival Prediction ◽  
Pancreatic Cancer Cells ◽  
The Impact

Abstract Background The DNA damage and repair pathway is considered a promising target for developing strategies against cancer. RAD51, also known as RECA, is a recombinase that performs the critical step in homologous recombination. RAD51 has recently received considerable attention due to its function in tumor progression and its decisive role in tumor resistance to chemotherapy. However, its role in pancreatic cancer has seldom been investigated. In this report, we provide evidence that RAD51, regulated by KRAS, promotes pancreatic cancer cell proliferation. Furthermore, RAD51 regulated aerobic glycolysis by targeting hypoxia inducible factor 1α (HIF1α). Methods TCGA (The Cancer Genome Atlas) dataset analysis was used to examine the impact of RAD51 expression on overall survival of pancreatic cancer patients. Lentivirus-mediated transduction was used to silence RAD51 and KRAS expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown effect. Analysis of the glycolysis process in pancreatic cancer cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Results Pancreatic cancer patients with higher levels of RAD51 exhibited worse survival. In pancreatic cancer cells, RAD51 positively regulated cell proliferation, decreased intracellular reactive oxygen species (ROS) production and increased the HIF1α protein level. KRAS/MEK/ERK activation increased RAD51 expression. In addition, RAD51 was a positive regulator of aerobic glycolysis. Conclusion The present study reveals novel roles for RAD51 in pancreatic cancer that are associated with overall survival prediction, possibly through a mechanism involving regulation of aerobic glycolysis. These findings may provide new predictive and treatment targets for pancreatic cancer.

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