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Pancreatic Neoplasms: HELP
Articles from Oxfordshire
Based on 130 articles published since 2008
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These are the 130 published articles about Pancreatic Neoplasms that originated from Oxfordshire during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Editorial Pancreatic cancer tissue banks: where are we heading? 2016

Balarajah, Vickna / Ambily, Archana / Dayem Ullah, Abu Z / Imrali, Ahmet / Dowe, Thomas / Al-Sarireh, Bilal / Abu Hilal, Mohammed / Davidson, Brian R / Soonawalla, Zahir / Metcalfe, Matthew / Chin Aleong, Jo-Anne / Chelala, Claude / Kocher, Hemant M. ·Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London, London, UK. · Barts Health NHS Trust, London, UK. · Abertawe Bro Morgannwg University Health Board, Port Talbot, UK. · University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Royal Free London NHS Foundation Trust, London, UK. · Oxford University Hospital NHS Foundation Trust, Oxford, UK. · University Hospital of Leicester NHS Trust, Leicester, UK. ·Future Oncol · Pubmed #27541064.

ABSTRACT: -- No abstract --

2 Editorial The role of radiotherapy in the management of upper gastrointestinal and hepato-biliary and pancreatic cancers: current status and future directions. 2014

Mukherjee, S / Symonds, R P. ·MRC/CRUK Oxford Institute for Radiation Oncology and Churchill Hospital, Oxford, UK. Electronic address: Somnath.mukherjee@oncology.ox.ac.uk. · Department of Cancer Studies & Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester, UK. ·Clin Oncol (R Coll Radiol) · Pubmed #24996376.

ABSTRACT: -- No abstract --

3 Review Diagnosis and management of pancreatic cancer in adults: A summary of guidelines from the UK National Institute for Health and Care Excellence. 2018

O'Reilly, Derek / Fou, Linyun / Hasler, Elise / Hawkins, James / O'Connell, Susan / Pelone, Ferruccio / Callaway, Mark / Campbell, Fiona / Capel, Margred / Charnley, Richard / Corrie, Pippa / Elliot, Dawn / Goodburn, Lesley / Jewell, Anna / Joharchi, Suzanne / McGeeney, Laura / Mukherjee, Somnath / Oppong, Kofi / Whelan, Phil / Primrose, John / Neoptolemos, John. ·Manchester Royal Infirmary, Central Manchester NHS Foundation Trust and University of Manchester, United Kingdom. Electronic address: doreilly@doctors.org.uk. · National Institute for Health and Care Excellence, United Kingdom. · Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, United Kingdom. · University of Liverpool, The Royal Liverpool & Broadgreen University Hospital NHS Trust, United Kingdom. · George Thomas Hospice, United Kingdom. · Freeman Hospital, Newcastle upon Tyne, United Kingdom. · Cambridge University Hospitals NHS Foundation Trust and University of Cambridge, United Kingdom. · Northumbria Healthcare Foundation Trust, United Kingdom. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany. · CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford & Churchill Hospital, United Kingdom. · University of Southampton, Southampton General Hospital, United Kingdom. · University of Heidelberg, Germany. ·Pancreatology · Pubmed #30292643.

ABSTRACT: To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.

4 Review Translational molecular imaging in exocrine pancreatic cancer. 2018

Cornelissen, Bart / Knight, James C / Mukherjee, Somnath / Evangelista, Laura / Xavier, Catarina / Caobelli, Federico / Del Vecchio, Silvana / Rbah-Vidal, Latifa / Barbet, Jacques / de Jong, Marion / van Leeuwen, Fijs W B. ·CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, UK. bart.cornelissen@oncology.ox.ac.uk. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, UK. · Istituto Oncologico Veneto I.R.C.C.S., Padova, Italy. · Vrije Universiteit Brussel, Brussels, Belgium. · Department of Radiology, Universitätsspital Basel, Basel, Switzerland. · Universita' degli Studi di Napoli "Federico II", Naples, Italy. · CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France. · Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. · Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. ·Eur J Nucl Med Mol Imaging · Pubmed #30225616.

ABSTRACT: Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management.

5 Review Molecular Genetic Studies of Pancreatic Neuroendocrine Tumors: New Therapeutic Approaches. 2018

Stevenson, Mark / Lines, Kate E / Thakker, Rajesh V. ·Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, UK. · Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, UK. Electronic address: rajesh.thakker@ndm.ox.ac.uk. ·Endocrinol Metab Clin North Am · Pubmed #30098714.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) arise sporadically or as part of familial syndromes. Genetic studies of hereditary syndromes and whole exome sequencing analysis of sporadic NETs have revealed the roles of some genes involved in PNET tumorigenesis. The multiple endocrine neoplasia type 1 (MEN1) gene is most commonly mutated. Its encoded protein, menin, has roles in transcriptional regulation, genome stability, DNA repair, protein degradation, cell motility and adhesion, microRNA biogenesis, cell division, cell cycle control, and epigenetic regulation. Therapies targeting epigenetic regulation and MEN1 gene replacement have been reported to be effective in preclinical models.

6 Review Management of pancreaticojejunal strictures after pancreaticoduodenectomy: clinical experience and review of literature. 2018

Ghazanfar, Mudassar A / Soonawalla, Zahir / Silva, Michael A / Reddy, Srikanth. ·Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. ·ANZ J Surg · Pubmed #28653509.

ABSTRACT: BACKGROUND: Symptomatic pancreaticojejunal anastomotic stricture (PJS) is a rare complication following pancreaticoduodenectomy. The incidence, presentation and management of this condition are infrequently reported in the literature. Revision surgery is thought to be an effective treatment. Recent literature shows some success from endoscopic management. METHODS: The patients treated for symptomatic PJS from January 2005 to June 2014 were identified. Their clinical presentation and management was retrospectively reviewed. Patients were followed up in clinic or by telephonic interviews to assess their symptoms. RESULTS: Three patients (two females and one male) had symptomatic PJS out of 314 who underwent pancreaticoduodenectomy (0.9%). Main presentating symptom was intermittent abdominal pain. The diagnosis was confirmed by computed tomography scan and/or magnetic resonance cholangiopancreatography. One patient underwent a failed endoscopic retrograde cholangiopancreatography attempt to dilate the stricture. A redo-pancreaticojejunostomy was performed in all patients. At a mean follow-up of 8 months, two patients had complete resolution of symptoms and one patient had partial benefit. Five out of seven case series in literature support surgical management. CONCLUSION: Symptomatic PJS can be successfully treated with redo-pancreaticojejunostomy, with good medium-term outcomes. Although endoscopic intervention has been described, review of the literature shows that success rates are low and the long-term results are unknown.

7 Review A meta-analysis of CXCL12 expression for cancer prognosis. 2017

Samarendra, Harsh / Jones, Keaton / Petrinic, Tatjana / Silva, Michael A / Reddy, Srikanth / Soonawalla, Zahir / Gordon-Weeks, Alex. ·Medical Sciences Division, University of Oxford, Oxford, UK. · CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK. · Cairns Library, John Radcliffe Hospital, Oxford, UK. · Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Trust, Oxford, UK. · Nuffield Department of Surgical Sciences, University of Oxford, Room 6607, Level 6, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK. ·Br J Cancer · Pubmed #28535157.

ABSTRACT: BACKGROUND: CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed. METHODS: We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival. RESULTS: Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective. The pooled hazard ratios (HRs) for overall and recurrence-free survival in patients with high CXCL12 expression were 1.39 (95% CI: 1.17-1.65, P=0.0002) and 1.12 (95% CI: 0.82-1.53, P=0.48) respectively, but with significant heterogeneity between studies. On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31-3.33, P=0.002), pancreatic (HR 1.54; 95% CI: 1.21-1.97, P=0.0005) and lung cancer (HR 1.37; 95% CI: 1.08-1.75, P=0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38-0.66, P<0.00001). CONCLUSIONS: Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types. Prospective or prospective-retrospective analyses of CXCL12 expression in clearly defined cancer cohorts are now required to advance our understanding of the relationship between CXCL12 expression and cancer outcome.

8 Review Medical management of secretory syndromes related to gastroenteropancreatic neuroendocrine tumours. 2016

Dimitriadis, Georgios K / Weickert, Martin O / Randeva, Harpal S / Kaltsas, Gregory / Grossman, Ashley. ·The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK Division of Translational and Experimental MedicineWarwick Medical School, University of Warwick, Coventry, UK Division of Endocrinology and Investigative MedicineImperial College London, Hammersmith Campus, London, UK g.dimitriadis@warwick.ac.uk. · The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK Division of Translational and Experimental MedicineWarwick Medical School, University of Warwick, Coventry, UK Centre for Applied Biological and Exercise SciencesCoventry University, Coventry, UK. · The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK Division of PathophysiologyNational and Kapodistrian University of Athens Medical School, Athens, Greece Oxford Center for DiabetesEndocrinology and Metabolism, University of Oxford, Oxford, UK. · Oxford Center for DiabetesEndocrinology and Metabolism, University of Oxford, Oxford, UK. ·Endocr Relat Cancer · Pubmed #27461388.

ABSTRACT: Although recent epidemiological evidence indicates that the prevalence of non-functioning gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) is rising, a significant number of GEP-NETs still present with symptoms related to the secretion of biologically active substances leading to the development of distinct clinical syndromes. In the past, these syndromes were associated with substantial morbidity and mortality due to the lack of specific therapies; however, since the introduction of long-acting somatostatin analogues and medications such as proton pump inhibitors, their control has been greatly improved. As a result, nowadays, the main cause of morbidity and mortality in GEP-NETs is mostly directly related to tumour growth and the extent of metastatic disease. However, in some patients with functioning tumours and extensive disease, control of the secretory syndrome still remains problematic, necessitating the employment of several cytoreductive techniques, which may not always be sufficient. Recently, new agents directed against tumour growth, or exerting increased binding activity to receptors expressed in these tumours, or interfering with the synthetic pathway of some of the compounds secreted by these tumours, have been developed. Since there are no specific guidelines addressing the totality of the management of the secretory syndromes related to GEP-NETs, this review aims at critically analysing the medical management of previously recognised secretory syndromes; it also addresses areas of uncertainty, assesses the newer therapeutic developments and also addresses recently described but poorly characterised secretory syndromes related to GEP-NETs.

9 Review Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. 2016

Allen, Victoria B / Gurusamy, Kurinchi Selvan / Takwoingi, Yemisi / Kalia, Amun / Davidson, Brian R. ·Oxford University Clinical Academic Graduate School, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK, OX3 9DU. ·Cochrane Database Syst Rev · Pubmed #27383694.

ABSTRACT: BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Laparoscopy can detect metastases not visualised on CT scanning, enabling better assessment of the spread of cancer (staging of cancer). This is an update to a previous Cochrane Review published in 2013 evaluating the role of diagnostic laparoscopy in assessing the resectability with curative intent in people with pancreatic and periampullary cancer. OBJECTIVES: To determine the diagnostic accuracy of diagnostic laparoscopy performed as an add-on test to CT scanning in the assessment of curative resectability in pancreatic and periampullary cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OvidSP (from inception to 15 May 2016), and Science Citation Index Expanded (from 1980 to 15 May 2016). SELECTION CRITERIA: We included diagnostic accuracy studies of diagnostic laparoscopy in people with potentially resectable pancreatic and periampullary cancer on CT scan, where confirmation of liver or peritoneal involvement was by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and quality assessment using the QUADAS-2 tool. The specificity of diagnostic laparoscopy in all studies was 1 because there were no false positives since laparoscopy and the reference standard are one and the same if histological examination after diagnostic laparoscopy is positive. The sensitivities were therefore meta-analysed using a univariate random-effects logistic regression model. The probability of unresectability in people who had a negative laparoscopy (post-test probability for people with a negative test result) was calculated using the median probability of unresectability (pre-test probability) from the included studies, and the negative likelihood ratio derived from the model (specificity of 1 assumed). The difference between the pre-test and post-test probabilities gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone. MAIN RESULTS: We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone.A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone. AUTHORS' CONCLUSIONS: Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned.

10 Review Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. 2015

Yates, Christopher J / Newey, Paul J / Thakker, Rajesh V. ·Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Diabetes and Endocrinology, Melbourne Health, Melbourne, VIC, Australia; Department of Diabetes and Endocrinology, Western Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia. · Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK; Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK. Electronic address: rajesh.thakker@ndm.ox.ac.uk. ·Lancet Diabetes Endocrinol · Pubmed #26165399.

ABSTRACT: Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder, is characterised by the occurrence of pancreatic neuroendocrine tumours (P-NETs) in association with parathyroid and pituitary tumours. P-NETs, which include gastrinomas, insulinomas, and non-functioning tumours, occur in more than 80% of MEN1 patients and account for 50% of disease-specific deaths. However, there is no consensus about the optimal methods for detecting and treating P-NETs in MEN1 patients, and extrapolations from approaches used in patients with non-familial (sporadic) P-NETs require caution because of differences, such as the younger age of onset, multi-focality of P-NETs, and concomitant presence of other tumours in MEN1 patients. Thus, the early detection of P-NETs by circulating biomarkers and imaging modalities, and their appropriate treatments by surgical approaches and/or radionuclide therapy, chemotherapy, and biotherapy pose challenges and controversies. These challenges and controversies will be reviewed and possible approaches proposed.

11 Review Comparison of toxicity after IMRT and 3D-conformal radiotherapy for patients with pancreatic cancer - a systematic review. 2015

Bittner, Martin-Immanuel / Grosu, Anca-Ligia / Brunner, Thomas B. ·Department of Radiation Oncology, University Medical Centre Freiburg, Germany; CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK(1). · Department of Radiation Oncology, University Medical Centre Freiburg, Germany. · Department of Radiation Oncology, University Medical Centre Freiburg, Germany. Electronic address: thomas.brunner@uniklinik-freiburg.de. ·Radiother Oncol · Pubmed #25497876.

ABSTRACT: IMRT has been suggested to reduce treatment-related toxicity in pancreatic cancer. We attempted to identify all IMRT-studies indexed in PubMed/Medline, comparing them with recent 3D-CRT trials. The predominant treatment-related toxicities, namely nausea/vomiting, diarrhoea and late GI toxicity, are significantly reduced with IMRT while there was no apparent difference for outcome measures.

12 Review Pancreatic ductal adenocarcinoma: From genetics to biology to radiobiology to oncoimmunology and all the way back to the clinic. 2015

Fokas, Emmanouil / O'Neill, Eric / Gordon-Weeks, Alex / Mukherjee, Somnath / McKenna, W Gillies / Muschel, Ruth J. ·Department of Oncology, Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK. Electronic address: emmanouil.fokas@oncology.ox.ac.uk. · Department of Oncology, Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK. · Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. ·Biochim Biophys Acta · Pubmed #25489989.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Despite improvements in the clinical management, the prognosis of PDAC remains dismal. In the present comprehensive review, we will examine the knowledge of PDAC genetics and the new insights into human genome sequencing and clonal evolution. Additionally, the biology and the role of the stroma in tumour progression and response to treatment will be presented. Furthermore, we will describe the evidence on tumour chemoresistance and radioresistance and will provide an overview on the recent advances in PDAC metabolism and circulating tumour cells. Next, we will explore the characteristics and merits of the different mouse models of PDAC. The inflammatory milieu and the immunosuppressive microenvironment mediate tumour initiation and treatment failure. Hence, we will also review the inflammatory and immune escaping mechanisms and the new immunotherapies tested in PDAC. A better understanding of the different mechanisms of tumour formation and progression will help us to identify the best targets for testing in future clinical studies of PDAC.

13 Review SBRT in pancreatic cancer: what is the therapeutic window? 2015

Brunner, Thomas B / Nestle, Ursula / Grosu, Anca-Ligia / Partridge, Mike. ·Department of Radiation Oncology, University Hospitals Freiburg, Germany. Electronic address: Thomas.brunner@uniklinik-freiburg.de. · Department of Radiation Oncology, University Hospitals Freiburg, Germany. · CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK. ·Radiother Oncol · Pubmed #25466369.

ABSTRACT: PURPOSE/OBJECTIVE: To analyse outcome and toxicity of stereotactic body radiotherapy (SBRT) in pancreatic cancer (PDAC). MATERIAL/METHODS: We systematically reviewed full reports on outcome and toxicity transforming prescription doses to equivalent doses of 2 Gy (EQD2) and biological equivalent doses (BED). Pearson product-moment correlation coefficient, regression analysis and Lyman-Kutcher-Burman modelling were used. RESULTS: Sixteen trials (572 patients) were identified. Local control correlated with dose. Additionally 4 upper gastrointestinal-SBRT trials (149 patients) were included for toxicity analysis. Acute toxicity was mild but late toxicity ⩾G2 was substantial and predominantly gastrointestinal. Late toxicity ⩾G2 and ⩾G3 correlated highly with EQD2/BED after linear (R(2)=0.85 and 0.77, respectively) and Lyman-Kutcher-Burman modelling. Linear regression lines indicated ⩾G2 and ⩾G3 toxicity frequencies of 5% at 65 Gy and 80 Gy EQD2-α/β=3, respectively. A comparison of toxicity with dose constraints for duodenum revealed partly inadequate dose constraints. CONCLUSION: RESULTS from multiple fraction regimens could be successfully interpreted to estimate toxicity according to EQD2/BED prescription doses, and dose constraints for the duodenum were derived, whereas local control appeared to be less dose-dependent. This analysis may be useful to plan clinical trials for SBRT and hypofractionated radiotherapy in pancreatic cancer.

14 Review Locally advanced pancreatic cancer: the role of definitive chemoradiotherapy. 2014

Huguet, F / Mukherjee, S / Javle, M. ·Service d'Oncologie Radiothérapie, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Paris, France. Electronic address: florence.huguet@tnn.aphp.fr. · Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Clin Oncol (R Coll Radiol) · Pubmed #25001636.

ABSTRACT: At the time of diagnosis, around 20% of patients with pancreatic cancer present at a resectable stage, 50% have metastatic disease and 30% have locally advanced tumour, non-metastatic but unresectable because of superior mesenteric artery or coeliac encasement. Despite advances in chemoradiotherapy and improved systemic chemotherapeutic agents, patients with locally advanced pancreatic cancer suffer from high rates of distant metastatic failure and from local progression, with a median survival time ranging from 5 to 11 months. In the past 30 years, modest improvements in median survival have been attained for these patients treated by chemoradiotherapy or chemotherapy protocols. The optimal therapy for patients with locally advanced pancreatic carcinoma remains controversial. This review aims to evaluate the role of radiotherapy for these patients.

15 Review Gastroenteropancreatic neuroendocrine (carcinoid) tumors in children. 2014

Johnson, Paul R V. ·Pediatric Surgery, University of Oxford, Oxford, UK; Oxford Islet Transplant Programme, Oxford, UK. Electronic address: paul.johnson@nds.ox.ac.uk. ·Semin Pediatr Surg · Pubmed #24931354.

ABSTRACT: Neuroendocrine tumors (NETs) (previously termed carcinoids) are slow-growing tumors of the neuroendocrine system. They can occur anywhere within the body but are most commonly found in the midgut. This review is therefore confined to a discussion of gastroenteropancreatic NETS (GEP-NETS). GEP-NETS may be asymptomatic and are found incidentally (eg, during appendicectomy) or can present with symptoms attributable to either the site of the primary tumor or the secretion of serotonin and other substances from metastatic carcinoid disease (carcinoid syndrome). Symptoms of carcinoid syndrome include facial flushing, diarrhea, wheezing, colicky abdominal pain, and edema. Surgical resection offers the only curative treatment for neuroendocrine tumors, although peptide hormone analogues can be used to control carcinoid symptoms. Guidelines exist to determine when further surgical resection is required when NETs (carcinoids) are found incidentally during appendicectomy. A multi-disciplinary approach is essential for the management of all children with these rare and challenging tumors.

16 Review The stromal compartments in pancreatic cancer: are there any therapeutic targets? 2014

Lunardi, Serena / Muschel, Ruth J / Brunner, Thomas B. ·Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Churchill Hospital, RRI, Oxford OX3 7LJ, UK. · Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Churchill Hospital, RRI, Oxford OX3 7LJ, UK; Department of Radiation Oncology, University Hospitals Freiburg, Robert-Koch-Straße 3, 79106 Freiburg, Germany. Electronic address: tbbrunner@gmail.com. ·Cancer Lett · Pubmed #24141189.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant stromal response also known as a desmoplastic reaction. Pancreatic Stellate Cells have been identified as playing a key role in pancreatic cancer desmoplasia. There is accumulating evidence that the stroma contributes to tumour progression and to the low therapeutic response of PDAC patients. In this review we described the main actors of the desmoplastic reaction within PDAC and novel therapeutic approaches that are being tested to block the detrimental function of the stroma.

17 Review Pleomorphic giant cell carcinoma of the pancreas with hepatic metastases--initially presenting as a benign serous cystadenoma: a case report and review of the literature. 2010

Athanasios, Petrou / Alexandros, Papalambros / Nicholas, Brennan / Dimitrios, Karles / Kostantinos, Bramis / Antonio, Manzelli / Efstathios, Papalambros. ·Department of Hepatobilary Surgery, Churchill Hospital, Oxford OX3 7LJ, UK. ·HPB Surg · Pubmed #21197435.

ABSTRACT: INTRODUCTION: Pleomorphic giant cell pancreatic cancer is a very rare and aggressive pancreatic neoplasm. A case of pleomorphic giant cell pancreatic cancer presenting as a cystic lesion and in association with a serous cystadenoma presents a unique case which has not been described before. CASE PRESENTATION: A 44-year-old alcoholic man presented with abdominal pain, vomiting, and weight loss. Initially, imaging suspected a pancreatic pseudocyst measuring 4.2 cm. Endoscopic ultrasound- (EUS-) guided fine-needle aspiration revealed a serous cystadenoma. With conservative intervention only (fluid resuscitation, analgesia, and antiemetics) the patient improved and was discharged under close observation. Follow-up scan at four months revealed minimal change. Three months later, he was admitted acutely. Repeat scans demonstrated mild cyst enlargement with new liver lesions. Laparoscopic biopsy revealed pleomorphic giant cell carcinoma with the organ of origin the pancreas. CONCLUSION: This unusual case highlights the challenges in managing pancreatic cystic lesions and emphasizes the importance of considering less common forms of pancreatic cystic masses when the findings are atypical for the presentation. Surgical excision in these cases over conservative steps may be the most appropriate management.

18 Review The role of radiotherapy in multimodal treatment of pancreatic carcinoma. 2010

Brunner, Thomas B / Scott-Brown, Martin. ·Gray Institute for Radiation Oncology & Biology, University of Oxford, Oxford, UK. thomas.brunner@rob.ox.ac.uk ·Radiat Oncol · Pubmed #20615227.

ABSTRACT: Pancreatic ductal carcinoma is one of the most lethal malignancies, but in recent years a number of positive developments have occurred in the management of pancreatic carcinoma. This article aims to give an overview of the current knowledge regarding the role of radiotherapy in the treatment of pancreatic ductal adenocarcinoma (PDAC). The results of meta-analyses, phase III-studies, and phase II-studies using chemoradiotherapy and chemotherapy for resectable and non-resectable PDAC were reviewed. The use of radiotherapy is discussed in the neoadjuvant and adjuvant settings as well as in the locally advanced situation. Whenever possible, radiotherapy should be performed as simultaneous chemoradiotherapy. Patients with PDAC should be offered entry into clinical trials to identify optimal treatment results.

19 Clinical Trial Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer. 2017

Hurt, C N / Falk, S / Crosby, T / McDonald, A / Ray, R / Joseph, G / Staffurth, J / Abrams, R A / Griffiths, G / Maughan, T / Mukherjee, S. ·Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK. · Bristol Haematology and Oncology Centre, Bristol BS2 8ED, UK. · Velindre Cancer Centre, Velindre Hospital, Velindre Road, Cardiff CF14 2TL, UK. · Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. · Department of Radiation Oncology, Rush University Medical Center, 500 S. Paulina, 013 Atrium Building, Chicago, IL 60612, USA. · Southampton Clinical Trials Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. · CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford OX3 7DQ, UK. ·Br J Cancer · Pubmed #28376080.

ABSTRACT: BACKGROUND: SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes. METHODS: Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks of induction GEMCAP chemotherapy (three cycles: GEM 1000 mg m RESULTS: One-hundred fourteen patients (28 UK centres) were registered between 24 December 2009 and 25 October 2011, and 74 were randomised (CAP-RT=36; GEM-RT=38). At the time of this analysis, 105 of the 114 patients had died and the surviving 9 patients had been followed up for a median of 10.9 months (IQR: 2.9-18.7). Updated median OS was 17.6 months (95% CI: 14.6-22.7) in the CAP-CRT arm and 14.6 months (95% CI: 11.1-16.0) in the GEM-CRT arm (intention-to-treat adjusted hazard ratio (HR): 0.68 (95% CI: 0.38-1.21, P=0.185)); median progression-free survival (PFS) was 12.0 months (95% CI: 10.0-15.2) in the CAP-CRT arm and 10.4 months (95% CI: 8.8-12.7) in the GEM-CRT arm (intention-to-treat adjusted HR: 0.60 (95% CI: 0.32-1.14, P=0.120)). In baseline multivariable model, age ⩾65 years, better performance status, CA19.9<613 IU l CONCLUSIONS: CAP-CRT remains the superior regimen. SCALOP showed that patients with CA19.9 <46 IU ml

20 Clinical Trial Correlation of 2017

Wilson, J M / Mukherjee, S / Brunner, T B / Partridge, M / Hawkins, M A. ·CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Oxford, UK. Electronic address: james.wilson@icr.ac.uk. · CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Oxford, UK. · Department of Radiation Oncology, University Hospitals Freiburg, Freiburg im Breisgau, Germany. ·Clin Oncol (R Coll Radiol) · Pubmed #28190636.

ABSTRACT: AIMS: A proportion of patients with pancreatic cancer never develop metastatic disease. We evaluated a role for MATERIAL AND METHODS: Patients with histologically confirmed LAPC entered a single-centre phase II study of definitive upfront chemoradiotherapy (CRT). All patients underwent FDG-PET/CT before and 6 weeks after CRT. Tumour volume, standardised uptake values (SUV RESULTS: Twenty-three patients with LAPC were recruited; 17/23 completed treatment and had interpretable sequential imaging. Twenty-four per cent of patients only ever experienced local disease. Median pre-CRT FDG-PET parameters were significantly lower in patients with local disease only during follow-up compared with those who developed metastatic disease: SUV CONCLUSIONS: Our findings suggest that patients with less FDG-avid tumours are less likely to metastasise and may therefore benefit from upfront local treatment intensification.

21 Clinical Trial Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. 2017

Neoptolemos, John P / Palmer, Daniel H / Ghaneh, Paula / Psarelli, Eftychia E / Valle, Juan W / Halloran, Christopher M / Faluyi, Olusola / O'Reilly, Derek A / Cunningham, David / Wadsley, Jonathan / Darby, Suzanne / Meyer, Tim / Gillmore, Roopinder / Anthoney, Alan / Lind, Pehr / Glimelius, Bengt / Falk, Stephen / Izbicki, Jakob R / Middleton, Gary William / Cummins, Sebastian / Ross, Paul J / Wasan, Harpreet / McDonald, Alec / Crosby, Tom / Ma, Yuk Ting / Patel, Kinnari / Sherriff, David / Soomal, Rubin / Borg, David / Sothi, Sharmila / Hammel, Pascal / Hackert, Thilo / Jackson, Richard / Büchler, Markus W / Anonymous8200894. ·University of Liverpool, Liverpool, UK; The Royal Liverpool University Hospital, Liverpool, UK. Electronic address: j.p.neoptolemos@liverpool.ac.uk. · University of Liverpool, Liverpool, UK; The Clatterbridge Cancer Centre, Wirral, UK. · The Royal Liverpool University Hospital, Liverpool, UK. · University of Liverpool, Liverpool, UK. · University of Manchester/The Christie NHS Foundation Trust, Manchester, UK. · University of Liverpool, Liverpool, UK; The Royal Liverpool University Hospital, Liverpool, UK. · The Clatterbridge Cancer Centre, Wirral, UK. · Manchester Royal Infirmary, Manchester, UK. · Royal Marsden Hospital, London, UK. · Weston Park Hospital, Sheffield, UK. · Royal Free Hospital, London, UK. · St James's University Hospital, Leeds, UK. · Karolinska Institute, Stockholm, Sweden; Clinical Research Sörmland, Eskilstuna, Sweden. · University of Uppsala, Uppsala, Sweden. · Bristol Haematology and Oncology Centre, Bristol, UK. · University of Hamburg Medical institutions UKE, Hamburg, Germany. · Royal Surrey County Hospital, Guildford, UK. · Guy's Hospital, London, UK. · Hammersmith Hospital, London, UK. · The Beatson West of Scotland Cancer Centre, Glasgow, UK. · Velindre Hospital, Cardiff, UK. · Queen Elizabeth Hospital, Birmingham, UK. · Churchill Hospital, Oxford, UK. · Derriford Hospital, Plymouth, UK. · Ipswich Hospital, Ipswich, UK. · Skåne University Hospital, Lund, Sweden. · University Hospital Coventry, Coventry, UK. · Hôpital Beaujon, Clichy, France. · University of Heidelberg, Germany. ·Lancet · Pubmed #28129987.

ABSTRACT: BACKGROUND: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. METHODS: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m FINDINGS: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group. INTERPRETATION: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma. FUNDING: Cancer Research UK.

22 Clinical Trial A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol. 2016

Holyoake, Daniel L P / Ward, Elizabeth / Grose, Derek / McIntosh, David / Sebag-Montefiore, David / Radhakrishna, Ganesh / Patel, Neel / Silva, Michael / Mukherjee, Somnath / Strauss, Victoria Y / Odondi, Lang'o / Fokas, Emmanouil / Melcher, Alan / Hawkins, Maria A. ·CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. · Oncology Clinical Trials Office, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. · The Beatson West of Scotland Cancer Centre, 1053 Great Western Rd, Glasgow, G12 0YN, UK. · The University of Leeds, Cancer Research UK Leeds Centre,14 Leeds Institute of Cancer and Pathology, Cancer Genetics Building, St James's University Hospital, 15 Beckett Street, Leeds, West Yorkshire, LS9 7TF, UK. · Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Bexley Wing, Beckett Street, Leeds, LS9 7TF, UK. · Oxford University Hospitals NHS Foundation Trust, Old Road, Headington, Oxford, OX3 7LE, UK. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UK. · The Institute of Cancer Research, Chester Beatty Laboratories, 237, Fulham Rd, London, SW3 6JB, UK. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. maria.hawkins@oncology.ox.ac.uk. ·BMC Cancer · Pubmed #27619800.

ABSTRACT: BACKGROUND: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control. METHODS/DESIGN: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. DISCUSSION: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options. TRIAL REGISTRATION: ISRCTN14138956 . Funded by CRUK.

23 Clinical Trial Comparison of investigator-delineated gross tumour volumes and quality assurance in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial. 2016

Fokas, Emmanouil / Spezi, Emiliano / Patel, Neel / Hurt, Chris / Nixon, Lisette / Chu, Kwun-Ye / Staffurth, John / Abrams, Ross / Mukherjee, Somnath. ·Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. · School of Engineering, Cardiff University, UK. · Oxford University Hospital NHS Foundation Trust, UK. · Wales Cancer Trials Unit, Centre for Trials Research, Cardiff University, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Oxford University Hospital NHS Foundation Trust, UK. · Institute of Cancer and Genetics, Cardiff University, UK; Cardiff NCRI RTTQA Centre, Velindre NHS Trust, UK. · Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Oxford University Hospital NHS Foundation Trust, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk. ·Radiother Oncol · Pubmed #27497804.

ABSTRACT: BACKGROUND AND PURPOSE: We performed a retrospective central review of tumour outlines in patients undergoing radiotherapy in the SCALOP trial. MATERIALS AND METHODS: The planning CT scans were reviewed retrospectively by a central review team, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was compared to the trials team-defined gold standard (gsGTV and gsPTV) using the Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI). The prognostic value of JCI and GMI was also assessed. The RT plans were also reviewed against protocol-defined constraints. RESULTS: 60 patients with diagnostic-quality planning scans were included. The median whole volume JCI for GTV was 0.64 (IQR: 0.43-0.82), and the median GMI was 0.11 (IQR: 0.05-0.22). For PTVs, the median JCI and GMI were 0.80 (IQR: 0.71-0.88) and 0.04 (IQR: 0.02-0.12) respectively. Tumour was completely missed in 1 patient, and⩾50% of the tumour was missed in 3. Patients with JCI for GTV⩾0.7 had 7.12 (95% CIs: 1.83-27.67, p=0.005) higher odds of progressing by 9months in multivariate analysis. Major deviations in RT planning were noted in 4.5% of cases. CONCLUSIONS: Radiotherapy workshops and real-time central review of contours are required in RT trials of pancreatic cancer.

24 Clinical Trial ARCII: A phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer. 2016

Wilson, James M / Fokas, Emmanouil / Dutton, Susan J / Patel, Neel / Hawkins, Maria A / Eccles, Cynthia / Chu, Kwun-Ye / Durrant, Lisa / Abraham, Aswin G / Partridge, Mike / Woodward, Martha / O'Neill, Eric / Maughan, Tim / McKenna, W Gillies / Mukherjee, Somnath / Brunner, Thomas B. ·Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. · Department of Radiology, Oxford University Hospitals NHS Foundation Trust, UK. · Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK. · Early Phase Research Hub, Department of Oncology, Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk. · Department of Radiation Oncology, University of Freiburg, Germany; German Cancer Consortium (DKTK), Heidelberg, Partner Site Freiburg, Germany. ·Radiother Oncol · Pubmed #27117177.

ABSTRACT: BACKGROUND AND PURPOSE: Nelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity. We conducted a phase II trial combining nelfinavir with chemoradiotherapy (CRT) for locally advanced inoperable pancreatic cancer (LAPC). MATERIALS AND METHODS: Radiotherapy (50.4Gy/28 fractions; boost to 59.4Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. Nelfinavir started 3-10days before and was continued during CRT. The primary end-point was 1-year overall survival (OS). Secondary end-points included histological downstaging, radiological response, 1-year progression free survival (PFS), overall survival (OS) and treatment toxicity. An imaging sub-study (n=6) evaluated hypoxia ((18)F-Fluoromisonidazole-PET) and perfusion (perfusion CT) during induction nelfinavir. RESULTS: The study closed after recruiting 23 patients, due to non-availability of Nelfinavir in Europe. The 1-year OS was 73.4% (90% CI: 54.5-85.5%) and median OS was 17.4months (90% CI: 12.8-18.8). The 1-year PFS was 21.8% (90% CI: 8.9-38.3%) and median PFS was 5.5months (90% CI: 4.1-8.3). All patients experienced Grade 3/4 toxicity, but many were asymptomatic laboratory abnormalities. Four of 6 patients on the imaging sub-study demonstrated reduced hypoxia and increased perfusion post-nelfinavir. CONCLUSIONS: CRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.

25 Clinical Trial miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial. 2016

Khan, Khurum / Cunningham, David / Peckitt, Clare / Barton, Sarah / Tait, Diana / Hawkins, Maria / Watkins, David / Starling, Naureen / Rao, Sheela / Begum, Ruwaida / Thomas, Janet / Oates, Jacqui / Guzzardo, Vincenza / Fassan, Matteo / Braconi, Chiara / Chau, Ian. ·Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK. · CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Oxford, UK. · Department of Medicine, University of Padua, Padua, IT. · Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK. ·Oncotarget · Pubmed #26862857.

ABSTRACT: BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/- cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. PATIENTS AND METHODS: This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels. RESULTS: 17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues. CONCLUSIONS: Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy.

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