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Pancreatic Neoplasms: HELP
Articles by Andrew G. Scarfe
Based on 6 articles published since 2009
(Why 6 articles?)
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Between 2009 and 2019, A. Scarfe wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Antiangiogenic agents in advanced gastrointestinal malignancies: past, present and a novel future. 2010

Mulder, Karen / Koski, Sheryl / Scarfe, Andrew / Chu, Quincy / King, Karen / Spratlin, Jennifer. ·Medical Oncology, Cross Cancer Institute, University of Alberta, Alberta, Canada. ·Oncotarget · Pubmed #21317448.

ABSTRACT: Advanced gastrointestinal (GI) malignancies are varied in presentation, prognosis, and treatment options. With the exception of resectable recurrent colorectal cancer, metastatic GI malignancies are incurable. Cytotoxic chemotherapies have been the mainstay of therapy for decades but limited extension of survival or clinical benefit has been achieved in non-colorectal GI cancers. There has been great interest in the incorporation of antiangiogenic strategies to improve outcomes for these patients. Clear benefits have been identified with bevacizumab and sorafenib in colorectal cancer and hepatocellular cancer, respectively; other GI tumor sites have lacked impressive results with antiangiogenic agents. In this review, we will present the benefits, or lack thereof, of clinically tested antiangiogenic compounds in GI malignancies and explore some potential new therapeutic anti-angiogenesis options for these diseases.

2 Clinical Trial Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. 2014

Valle, Juan W / Palmer, Daniel / Jackson, Richard / Cox, Trevor / Neoptolemos, John P / Ghaneh, Paula / Rawcliffe, Charlotte L / Bassi, Claudio / Stocken, Deborah D / Cunningham, David / O'Reilly, Derek / Goldstein, David / Robinson, Bridget A / Karapetis, Christos / Scarfe, Andrew / Lacaine, Francois / Sand, Juhani / Izbicki, Jakob R / Mayerle, Julia / Dervenis, Christos / Oláh, Attila / Butturini, Giovanni / Lind, Pehr A / Middleton, Mark R / Anthoney, Alan / Sumpter, Kate / Carter, Ross / Büchler, Markus W. ·Juan W. Valle, Derek O'Reilly, Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust and University of Manchester, Manchester · Richard Jackson, Trevor Cox, John P. Neoptolemos, Paula Ghaneh, Charlotte L. Rawcliffe, Liverpool Cancer Research UK Centre and the National Institute for Health Research Pancreas Biomedical Research Unit, University of Liverpool, Liverpool · Daniel Palmer, the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust · Deborah D. Stocken, the Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham · David Cunningham, Royal Marsden Hospital Foundation Trust, Sutton · Mark R. Middleton, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford · Alan Anthoney, The Leeds Teaching Hospital Trust, Leeds · Kate Sumpter, Freeman Hospital, Newcastle upon Tyne · Ross Carter, Glasgow Royal Infirmary, Glasgow, United Kingdom · Claudio Bassi, Giovanni Butturini, University of Verona, Verona, Italy · David Goldstein, Bridget A. Robinson, Christos Karapetis, the Australasian Gastro-Intestinal Trials Group, Camperdown, Australia · Andrew Scarfe, University of Alberta, Edmonton, Canada · Francois Lacaine, Hôpital TENON, Assistance Publique Hôpitaux de Paris, Universite Pierre Et Marie Curie, Paris, France · Juhani Sand, Tampere University Hospital, Tampere, Finland · Jakob R. Izbicki, University of Hamburg, Hamburg · Julia Mayerle, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald · Markus W. Büchler, University of Heidelberg, Heidelberg, Germany · Christos Dervenis, the Agia Olga Hospital, Athens, Greece · Attila Oláh, the Petz Aladar Hospital, Gyor, Hungary · Pehr A. Lind, Karolinska-Stockholm Söder Hospital, Stockholm, Sweden. ·J Clin Oncol · Pubmed #24419109.

ABSTRACT: PURPOSE: Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown. PATIENTS AND METHODS: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy. RESULTS: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001). CONCLUSION: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.

3 Clinical Trial Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. 2012

Neoptolemos, John P / Moore, Malcolm J / Cox, Trevor F / Valle, Juan W / Palmer, Daniel H / McDonald, Alexander C / Carter, Ross / Tebbutt, Niall C / Dervenis, Christos / Smith, David / Glimelius, Bengt / Charnley, Richard M / Lacaine, François / Scarfe, Andrew G / Middleton, Mark R / Anthoney, Alan / Ghaneh, Paula / Halloran, Christopher M / Lerch, Markus M / Oláh, Attila / Rawcliffe, Charlotte L / Verbeke, Caroline S / Campbell, Fiona / Büchler, Markus W / Anonymous1780731. ·Institute of Translational Medicine, Liverpool Cancer Trials Unit, Liverpool Cancer Research United Kingdom Centre, University of Liverpool, Liverpool, England, United Kingdom. j.p.neoptolemos@liverpool.ac.uk ·JAMA · Pubmed #22782416.

ABSTRACT: CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

4 Article Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy. 2018

Elander, N O / Aughton, K / Ghaneh, P / Neoptolemos, J P / Palmer, D H / Cox, T F / Campbell, F / Costello, E / Halloran, C M / Mackey, J R / Scarfe, A G / Valle, J W / McDonald, A C / Carter, R / Tebbutt, N C / Goldstein, D / Shannon, J / Dervenis, C / Glimelius, B / Deakin, M / Charnley, R M / Anthoney, A / Lerch, M M / Mayerle, J / Oláh, A / Büchler, M W / Greenhalf, W / Anonymous1351258. ·Cancer Research U.K. Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK. · Cross Cancer Institute and University of Alberta, Edmonton, Canada. · University of Manchester/The Christie NHS Foundation Trust, Manchester, UK. · The Beatson West of Scotland Cancer Centre, Glasgow, UK. · Glasgow Royal Infirmary, Glasgow, UK. · Austin Health, Melbourne, VIC, Australia. · Prince of Wales hospital and Clinical School, University of New South Wales, Sydney, NSW, Australia. · Nepean Cancer Centre and University of Sydney, Camperdown, NSW, Australia. · The Agia Olga Hospital, Athens, Greece. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · University Hospital, North Staffordshire, Staffordshire, UK. · Freeman Hospital, Newcastle upon Tyne, UK. · St James's University Hospital, Leeds, UK. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine II, University Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany. · The Petz Aladar Hospital, Gyor, Hungary. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Cancer Research U.K. Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK. greenhaf@liv.ac.uk. ·Br J Cancer · Pubmed #29523831.

ABSTRACT: BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

5 Article Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer. 2018

Elander, N O / Aughton, K / Ghaneh, P / Neoptolemos, J P / Palmer, D H / Cox, T F / Campbell, F / Costello, E / Halloran, C M / Mackey, J R / Scarfe, A G / Valle, J W / McDonald, A C / Carter, R / Tebbutt, N C / Goldstein, D / Shannon, J / Dervenis, C / Glimelius, B / Deakin, M / Charnley, R M / Anthoney, Alan / Lerch, M M / Mayerle, J / Oláh, A / Büchler, M W / Greenhalf, W / Anonymous1151214. ·From the Cancer Research U.K. Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK. · The Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Cross Cancer Institute and University of Alberta, Alberta, Canada. · University of Manchester/The Christie NHS Foundation Trust, Manchester, UK. · The Beatson West of Scotland Cancer Centre, Glasgow, Scotland, UK. · Glasgow Royal Infirmary, Glasgow, Scotland, UK. · Austin Health, Melbourne, Australia. · Prince of Wales hospital and Clinical School University of New South Wales, New South Wales, Australia. · Nepean Cancer Centre and University of Sydney, Sydney, Australia. · The Agia Olga Hospital, Athens, Greece. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · University Hospital, North Staffordshire, UK. · Freeman Hospital, Newcastle upon Tyne, UK. · St James's University Hospital, Leeds, UK. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine II, University Hospital of the Ludwig-Maximilians-University, Munich, Germany. · The Petz Aladar Hospital, Gyor, Hungary. · From the Cancer Research U.K. Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK. greenhaf@liv.ac.uk. ·Br J Cancer · Pubmed #29515256.

ABSTRACT: BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

6 Article Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. 2014

Greenhalf, William / Ghaneh, Paula / Neoptolemos, John P / Palmer, Daniel H / Cox, Trevor F / Lamb, Richard F / Garner, Elizabeth / Campbell, Fiona / Mackey, John R / Costello, Eithne / Moore, Malcolm J / Valle, Juan W / McDonald, Alexander C / Carter, Ross / Tebbutt, Niall C / Goldstein, David / Shannon, Jennifer / Dervenis, Christos / Glimelius, Bengt / Deakin, Mark / Charnley, Richard M / Lacaine, François / Scarfe, Andrew G / Middleton, Mark R / Anthoney, Alan / Halloran, Christopher M / Mayerle, Julia / Oláh, Attila / Jackson, Richard / Rawcliffe, Charlotte L / Scarpa, Aldo / Bassi, Claudio / Büchler, Markus W / Anonymous5150777. ·Affiliations of authors: Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK (WG, JPN, EG, TFC, PG, EC, CMH, CLR, FC, RJ) · the Princess Margaret Hospital, Toronto, Canada (MJM) · Manchester Academic Health Sciences Centre, Christie NHS Foundation Trust, School of Cancer and Enabling Sciences, University of Manchester, UK (JWV) · Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK (DHP) · Beatson West of Scotland Cancer Centre, Glasgow, UK (ACM) · Glasgow Royal Infirmary, Glasgow, UK (RC) · Hôpital Tenon, Université, Pierre et Marie Curie, Paris, France (FL) · Austin Health, Melbourne, Australia (NCT) · Prince of Wales Hospital and Clinical School University of New South Wales, New South Wales, Australia (DG) · Nepean Cancer Centre and University of Sydney, Sydney, Australia (JS) · Agia Olga Hospital, Athens, Greece (CD) · Medical Oncology, Clatterbridge Centre for Oncology, Bebington, Merseyside, UK (DS) · Department of Oncology, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden (BG) · University Hospital, North Staffordshire, UK (MD) · Freeman Hospital, Newcastle upon Tyne, UK (RMC) · Service de Chirurgie Digestive et Viscérale, Hôpital Tenon, Paris, France (FL) · Cross Cancer Institute and University of Alberta, Alberta, Canada (JRM, AGS) · Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK (MRM) · St James's University Hospital, Leeds, UK (AA) · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany (JM) · Petz Aladar Hospital, Gyor, Hungary (AO) · Departments of Surgery and Pathology and ARC-NET Research Center, University of Verona, Italy (AS, CB) · Department of Surgery, University of Heidelberg, Heidelberg, Germany (MWB). ·J Natl Cancer Inst · Pubmed #24301456.

ABSTRACT: BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. METHODS: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients. CONCLUSIONS: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.