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Pancreatic Neoplasms: HELP
Articles by Nick Pavlakis
Based on 15 articles published since 2010
(Why 15 articles?)
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Between 2010 and 2020, N. Pavlakis wrote the following 15 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Escalated-dose somatostatin analogues for antiproliferative effect in GEPNETS: a systematic review. 2017

Chan, David L / Ferone, Diego / Albertelli, Manuela / Pavlakis, Nick / Segelov, Eva / Singh, Simron. ·Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. · Sydney Medical School, University of Sydney, Camperdown, NSW, Australia. · Endocrinology, Department of Internal Medicine and Medical Specialties, IRCCS AOU San Martino-IST, Center of Excellence for Biomedical Research, University of Genova, Genova, Italy. · Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia. · Medical Oncology, Monash Health and Monash University, Caulfield East, VIC, Australia. · Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. simron.singh@sunnybrook.ca. ·Endocrine · Pubmed #28726183.

ABSTRACT: BACKGROUND/PURPOSE: Somatostatin analogues are the cornerstone of systemic therapy for metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours for both hormonal control and antiproliferative effect. Dose escalation of somatostatin analogues is often utilized in clinical practice, but small studies have yielded mixed results. The aim of this study was to systematically determine the efficacy and safety of escalated-dose somatostatin analogues in the above setting. METHODS: Eligible trials (using more than 30 mg octreotide or 120 mg lanreotide/28 days) were identified from MEDLINE, EMBASE, other databases and conference proceedings. Demographics, disease control rate, objective response rate, biochemical response, improvement in symptoms and toxicity were abstracted. Trials were synthesized qualitatively. RESULTS: Eighteen studies (1002 patients) were identified. The risk of bias was moderate for objective response outcomes, but high for the outcomes of symptom control and toxicity due to open-label trial designs. Disease control rates ranged from 30 to 100%, but response rates were modest (at 0-14%). Rates of biochemical improvement (27-100%) and symptom improvement (23-100%) ranged widely depending on the population studied and the definition of response. The most common toxicities were fatigue, diarrhoea, abdominal discomfort and cholelithiasis, with no severe or unexpected toxicities compared to standard-dose somatostatin analogues. CONCLUSIONS: The current evidence indicates that escalated-dose somatostatin analogues are well-tolerated in patients with gastroenteropancreatic neuroendocrine tumours, with significant rates of disease control but low rates of tumour response. It was difficult to judge the exact rate of biochemical response or symptomatic improvement. There is a need for large, prospective studies investigating the role of escalated-dose somatostatin analogues in the treatment of metastatic gastroenteropancreatic neuroendocrine tumours.

2 Clinical Trial Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial. 2015

Chantrill, Lorraine A / Nagrial, Adnan M / Watson, Clare / Johns, Amber L / Martyn-Smith, Mona / Simpson, Skye / Mead, Scott / Jones, Marc D / Samra, Jaswinder S / Gill, Anthony J / Watson, Nicole / Chin, Venessa T / Humphris, Jeremy L / Chou, Angela / Brown, Belinda / Morey, Adrienne / Pajic, Marina / Grimmond, Sean M / Chang, David K / Thomas, David / Sebastian, Lucille / Sjoquist, Katrin / Yip, Sonia / Pavlakis, Nick / Asghari, Ray / Harvey, Sandra / Grimison, Peter / Simes, John / Biankin, Andrew V / Anonymous5550827 / Anonymous5560827. ·The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. andrew.biankin@glasgow.ac.uk l.chantrill@garvan.org.au. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. Crown Princess Mary Cancer Centre, Westmead, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Prince of Wales Hospital, Randwick, New South Wales, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. · University of Sydney, New South Wales, Australia. Macquarie University Hospital, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. Department of Surgery, Bankstown Hospital, Sydney, New South Wales, Australia. South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, New South Wales, Australia. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. · NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. · Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. · Northern Sydney Cancer Centre, Royal North Shore Hospital, New South Wales, Australia. · Bankstown Cancer Centre, Bankstown, New South Wales, Australia. · Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. · Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. Department of Surgery, Bankstown Hospital, Sydney, New South Wales, Australia. South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, New South Wales, Australia. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. andrew.biankin@glasgow.ac.uk l.chantrill@garvan.org.au. ·Clin Cancer Res · Pubmed #25896973.

ABSTRACT: PURPOSE: Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. EXPERIMENTAL DESIGN: The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). RESULTS: Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. CONCLUSIONS: Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options.

3 Article Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: A multi-institutional cohort study. 2019

Nahm, Christopher B / Turchini, John / Jamieson, Nigel / Moon, Elizabeth / Sioson, Loretta / Itchins, Malinda / Arena, Jennifer / Colvin, Emily / Howell, Viive M / Pavlakis, Nick / Clarke, Stephen / Samra, Jaswinder S / Gill, Anthony J / Mittal, Anubhav. ·The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: anubhav.mittal@sydney.edu.au. ·Eur J Surg Oncol · Pubmed #30348604.

ABSTRACT: BACKGROUND: Up to 60% of patients who undergo curative-intent pancreatic ductal adenocarcinoma (PDAC) resection experience disease recurrence within six months. We recently published a systematic review of prognostic immunohistochemical biomarkers in PDAC and shortlisted a panel of those reported with the highest level of evidence, including p53, p16, Ca-125, S100A4, FOXC1, EGFR, mesothelin, CD24 and UPAR. This study aims to discover and validate the prognostic significance of a combinatorial panel of tumor biomarkers in patients with resected PDAC. METHODS: Patients who underwent PDAC resection were included from a single institution discovery cohort and a multi-institutional validation cohort. Tumors in the discovery cohort were stained immunohistochemically for all nine shortlisted biomarkers. Biomarkers significantly associated with overall survival (OS) were reevaluated as a combinatorial panel in both discovery and validation cohorts for its prognostic significance. RESULTS: 224 and 191 patients were included in the discovery and validation cohorts, respectively. In both cohorts, S100A4, Ca-125 and mesothelin expression were associated with shorter OS. In both cohorts, the number of these biomarkers expressed was significantly associated with OS (discovery cohort 36.8 vs. 26.4 vs 16.3 vs 12.8 months, P < 0.001; validation cohort 25.2 vs 18.3 vs 13.6 vs 11.9 months, P = 0.008 for expression of zero, one, two and three biomarkers, respectively). On multivariable analysis, expression of at least one of three biomarkers was independently associated with shorter OS. CONCLUSION: Combinations of S100A4, Ca-125 and mesothelin expression stratify survival after resection of localized PDAC. Co-expression of all three biomarkers is associated with the poorest prognostic outcome.

4 Article Follow-up Recommendations for Completely Resected Gastroenteropancreatic Neuroendocrine Tumors. 2018

Singh, Simron / Moody, Lesley / Chan, David L / Metz, David C / Strosberg, Jonathan / Asmis, Timothy / Bailey, Dale L / Bergsland, Emily / Brendtro, Kari / Carroll, Richard / Cleary, Sean / Kim, Michelle / Kong, Grace / Law, Calvin / Lawrence, Ben / McEwan, Alexander / McGregor, Caitlin / Michael, Michael / Pasieka, Janice / Pavlakis, Nick / Pommier, Rodney / Soulen, Michael / Wyld, David / Segelov, Eva / Anonymous4510956. ·Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. · Perelman School of Medicine, Department of Gastroenterology, University of Pennsylvania, Philadelphia. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Centre, Tampa, Florida. · Department of Internal Medicine, University of Ottawa, Ottawa, Ontario, Canada. · Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia. · Department of Medical Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco. · North American Neuroendocrine Tumor Society, Albany, New York. · Department of Endocrinology, Wellington Regional Hospital, Wellington, New Zealand. · Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada. · Department of Gastroenterology, Mount Sinai Hospital, New York, New York. · Department of Nuclear Medicine, Peter MacCullum Cancer Centre, Melbourne, Australia. · Department of Surgery, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · Department of Medical Oncology, Auckland Hospital, Auckland, New Zealand. · Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. · Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · Department of Medical Oncology, Peter MacCullum Cancer Centre, Melbourne, Australia. · Department of Surgery, Tom Baker Cancer Centre, Calgary, Alberta, Canada. · Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia. · Department of Surgery, Oregon Health & Science University, Portland. · Perelman School of Medicine, Department of Medical Imaging, University of Pennsylvania, Philadelphia. · Department of Medical Oncology, Royal Brisbane and Women's Hospital, Queensland, Australia. · Department of Medical Oncology, Monash University, Clayton, Australia. ·JAMA Oncol · Pubmed #30054622.

ABSTRACT: There is no consensus on optimal follow-up for completely resected gastroenteropancreatic neuroendocrine tumors. Published guidelines for follow-up are complex and emphasize closer surveillance in the first 3 years after resection. Neuroendocrine tumors have a different pattern and timescale of recurrence, and thus require more practical and tailored follow-up. The Commonwealth Neuroendocrine Tumour Collaboration convened an international multidisciplinary expert panel, in collaboration with the North American Neuroendocrine Tumor Society, to create patient-centered follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors. This panel used the RAND/UCLA (University of California, Los Angeles) Appropriateness Method to generate recommendations. A large international survey was conducted outlining current the surveillance practice of neuroendocrine tumor practitioners and shortcomings of the current guidelines. A systematic review of available data to date was supplemented by recurrence data from 2 large patient series. The resultant guidelines suggest follow-up for at least 10 years for fully resected small-bowel and pancreatic neuroendocrine tumors and also identify clinical situations in which no follow-up is required. These recommendations stratify follow-up strategies based on evidence-based prognostic factors that allow for a more individualized patient-centered approach to this complex and heterogeneous malignant neoplasm.

5 Article External Beam Radiotherapy in the Treatment of Gastroenteropancreatic Neuroendocrine Tumours: A Systematic Review. 2018

Chan, D L / Thompson, R / Lam, M / Pavlakis, N / Hallet, J / Law, C / Singh, S / Myrehaug, S. ·Department of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. · Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. · University of Western Ontario, London, Canada. · Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia. · Department of Surgical Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. · Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address: sten.myrehaug@sunnybrook.ca. ·Clin Oncol (R Coll Radiol) · Pubmed #29615284.

ABSTRACT: AIMS: External beam radiotherapy (EBRT) is infrequently used to treat gastroenteropancreatic neuroendocrine tumours (GEPNETS), with little published data to date. We carried out a systematic review to assess the activity of EBRT for GEPNETS. MATERIALS AND METHODS: Major databases were searched for papers including at least five patients treated with contemporary EBRT techniques. Eligible studies underwent dual independent review. The primary end points were response rate for lesions treated with definitive intent and recurrence-free survival for primary lesions treated with neoadjuvant or adjuvant intent. RESULTS: Of 11 included studies (all retrospective), seven investigated pancreatic neuroendocrine tumours (PNETs, 100 patients, 14% grade 3) and four studies investigated extra-pancreatic neuroendocrine tumours (84 patients, 14% grade 3). Trials investigating PNETs administered a median of 50.4 Gy via three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. EBRT was given with neoadjuvant or adjuvant intent in 56 patients, with a recurrence rate of 15%. For the 44 patients not undergoing surgery, the radiological response rate was 46%. Grade 3 + toxicity rates were 11% (acute) and 4% (late). Twelve patients with anorectal neuroendocrine carcinoma received 58 Gy to the primary tumour. Seventy-two patients were treated to sites of metastatic disease (34 bone, 27 brain, 11 soft tissue). Local and distant control were poorly reported. Overall survival ranged from 9 to 19 months. No studies in this group reported toxicity outcomes. CONCLUSIONS: There are limited, retrospective data on the overall activity and safety of EBRT in GEPNETS. EBRT generally seems to be well tolerated in selected PNET patients with encouraging activity. Well-designed prospective studies in clearly defined populations are required to clarify the role of EBRT in neuroendocrine tumours.

6 Article Follow-Up for Resected Gastroenteropancreatic Neuroendocrine Tumours: A Practice Survey of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and the North American Neuroendocrine Tumor Society (NANETS). 2018

Chan, David L / Moody, Lesley / Segelov, Eva / Metz, David C / Strosberg, Jonathan R / Pavlakis, Nick / Singh, Simron. ·Department of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. · Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia. · Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. · Department of Oncology, Monash Health and Monash University, Melbourne, Victoria, Australia. · Division of Gastroenterology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA. · Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA. · Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia. ·Neuroendocrinology · Pubmed #29539613.

ABSTRACT: OBJECTIVES: There is no consensus regarding optimal follow-up in resected gastroenteropancreatic neuroendocrine tumours (NETs). We aimed to perform a practice survey to ascertain follow-up patterns by health care practitioners and highlight areas of variation that may benefit from further quantitative research. METHODS: A Web-based survey targeted at NET health care providers in Australia, New Zealand, Canada, and the USA was developed by a steering committee of medical oncologists and a research methodologist. Thirty-seven questions elicited information regarding adherence to guidelines, the influence of risk factors on follow-up, and the frequency and choice of modality in follow-up. RESULTS: There were 163 respondents: 59 from Australia, 25 from New Zealand, 46 from Canada, and 33 from the USA (50% medical oncology, 23% surgery, 13% nuclear medicine, and 15% other). Thirty-eight percent of the respondents were "very familiar" with the NCCN NET guidelines, 33% with the ENETS guidelines, and 17% with the ESMO guidelines; however, only 15, 27, and 10%, respectively, found them "very useful"; 63% reported not using guidelines at their institution. The commonest investigations used were CT scans (66%) and chromogranin A (86%). The US respondents were more likely to follow patients up past 5 years, and the Australian respondents utilized more functional and less cross-sectional imaging. When poor prognostic factors were introduced, the respondents recommended more visits and tests. CONCLUSIONS: This large international survey highlights variation in current follow-up practices not well addressed by the current guidelines. More quantitative research is required to inform the development of evidence-based guidelines tailored to the pattern of recurrence in NETs.

7 Article Histopathological tumour viability after neoadjuvant chemotherapy influences survival in resected pancreatic cancer: analysis of early outcome data. 2018

Townend, Phil / de Reuver, Phil R / Chua, Terence C / Mittal, Anubhav / Clark, Stephen J / Pavlakis, Nick / Gill, Anthony J / Samra, Jaswinder S. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Discipline of Surgery, The University of Sydney, Sydney, New South Wales, Australia. · Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney, New South Wales, Australia. · Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia. · Deparment of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Macquarie University Hospital, Macquarie University, Sydney, New South Wales, Australia. ·ANZ J Surg · Pubmed #28318082.

ABSTRACT: BACKGROUND: Neoadjuvant therapy is increasingly recognized as an effective strategy prior to pancreatoduodenectomy. We investigate the role of neoadjuvant chemotherapy (NAC) followed by surgery and the predictive role of viable residual tumour cells histopathologically on outcomes. METHODS: The study population comprised of 195 consecutive patients with pancreatic adenocarcinoma who were treated with either NAC or a surgery-first (SF) strategy. Histopathological viable tumour cells were examined in the NAC patients and clinicopathological factors were correlated with overall survival. RESULTS: Forty-two patients (22%) were treated with NAC and 153 patients (78%) underwent SF. NAC was associated with higher estimated blood loss during surgery (928 mL versus 615 mL; P = 0.004), fewer (<15) excised lymph nodes (37% versus 17%; P = 0.015) and lower rates of lymphovascular invasion (65% versus 45%; P = 0.044) when compared with SF. Two-year survival of patients undergoing NAC was 63% and 51% in patients undergoing SF (P = 0.048). The 2-year survival of patients who had >65% residual tumour cells was 45% and 90% in patients who had <65% residual tumour cells (P = 0.022). Favourable responders (<65% viable tumour cells) were observed to have shorter operation time (<420 min) (55% versus 13%; P = 0.038), trend towards negative lymph node status (38% versus 10%; P = 0.067) and greater lymph node harvest in node positive patients (≥4 positive lymph nodes) (77% versus 37%; P = 0.045). CONCLUSION: The improved survival of patients undergoing NAC indicates effective management of micrometastatic disease and is an effective option requiring further investigation. Histopathological viable tumour cells after NAC was a surrogate marker for survival.

8 Article Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high volume referral centre. 2017

Itchins, M / Arena, J / Nahm, C B / Rabindran, J / Kim, S / Gibbs, E / Bergamin, S / Chua, T C / Gill, A J / Maher, R / Diakos, C / Wong, M / Mittal, A / Hruby, G / Kneebone, A / Pavlakis, N / Samra, J / Clarke, S. ·Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia. Electronic address: mitchins@gmail.com. · Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia. · Upper GI Surgical Unit, Department of Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia. · Upper GI Surgical Unit, Department of Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, NSW, Australia. · National Health and Medical Research Council Clinical Trial Centre (NHMRC CTC), The University of Sydney, Australia. · Sydney Medical School (Northern), The University of Sydney, Australia; Cancer Diagnosis and Pathology, Kolling Institute, Royal North Shore Hospital, Sydney, Australia. · Department of Radiology, Royal North Shore Hospital, Australia. · Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia; Northern Cancer Institute, Sydney, NSW, Australia. · Department of Medical Oncology, Gosford Hospital, New South Wales, Australia. · Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia. ·Eur J Surg Oncol · Pubmed #28688722.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to surgery provides promise. In the absence of prospective data, well annotated clinical data from high-volume units may provide pilot data for randomised trials. METHODS: Medical records from a tertiary hospital in Sydney, Australia, were analysed to identify all patients with resectable or borderline resectable PDAC. Data regarding treatment, toxicity and survival were collected. RESULTS: Between January 1 2010 and April 1 2016, 220 sequential patients were treated: 87 with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5 UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline patients received NA RT, 22 sequential to NAC. The median overall survival (OS) in the NA group was 25.9 months (mo); 95% CI (21.1-43.0 mo) compared to 26.9 mo (19.7, 32.7) in the UO; HR 0.89; log-ranked p-value = 0.58. Sixty-nine NA patients (79%) were resected, mOS was 29.2 mo (22.27, not reached (NR)). Twenty-two NA (31%) versus 22 UO (17%) were node negative at operation (N0). In those managed with NAC/RT the mOS was 29.0 mo (17.3, NR). There were no post-operative deaths with NA within 90-days and three in the UO arm. DISCUSSION: This is a hypothesis generating retrospective review of a selected real-world population in a high-throughput unit. Treatment with NA was well tolerated. The long observed survival in this group may be explained by lymph node sterilisation by NA, and the achievement of R0 resection in a greater proportion of patients.

9 Article Lost in translation: returning germline genetic results in genome-scale cancer research. 2017

Johns, Amber L / McKay, Skye H / Humphris, Jeremy L / Pinese, Mark / Chantrill, Lorraine A / Mead, R Scott / Tucker, Katherine / Andrews, Lesley / Goodwin, Annabel / Leonard, Conrad / High, Hilda A / Nones, Katia / Patch, Ann-Marie / Merrett, Neil D / Pavlakis, Nick / Kassahn, Karin S / Samra, Jaswinder S / Miller, David K / Chang, David K / Pajic, Marina / Anonymous6590904 / Pearson, John V / Grimmond, Sean M / Waddell, Nicola / Zeps, Nikolajs / Gill, Anthony J / Biankin, Andrew V. ·Cancer Research Program, Garvan Institute of Medical Research, Kinghorn Cancer Centre, Sydney, Australia. · St Vincents Hospital, Darlinghurst, Australia. · Western Sydney University Clinical School, Sydney, Australia. · Genetics Department, SEALS Pathology, Prince of Wales Hospital, Randwick, Sydney, Australia. · School of Medicine, University of New South Wales, Sydney, Australia. · Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, Sydney, Australia. · Cancer Genetics Department, Royal Prince Alfred Hospital and Liverpool Hospital, Sydney, NSW, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Australia. · Sydney Cancer Genetics, Sydney, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, Australia. · Division of Surgery, School of Medicine, Western Sydney University, Sydney, Australia. · Department of Medical Oncology, Royal North Shore Hospital and Faculty of Medicine, University of Sydney, Sydney, Australia. · Genetic and Molecular Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, Australia. · Department of Surgery, Royal North Shore Hospital, Sydney, Australia. · Illumina Inc, 5200 Illumina Way, San Diego, CA, 92122, USA. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. · University of Melbourne, Parkville, Australia. · St John of God Subiaco, Perth, Australia. · School of Surgery, The University of Western Australia, Perth, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Australia and University of Sydney, Sydney, Australia. · Cancer Research Program, Garvan Institute of Medical Research, Kinghorn Cancer Centre, Sydney, Australia. andrew.biankin@glasgow.ac.uk. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. andrew.biankin@glasgow.ac.uk. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. andrew.biankin@glasgow.ac.uk. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, UK. andrew.biankin@glasgow.ac.uk. ·Genome Med · Pubmed #28454591.

ABSTRACT: BACKGROUND: The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned. Using this experience, we discuss barriers and opportunities associated with a comprehensive process of RoR in large-scale genomic research that may be useful for others developing their own policies. METHODS: We performed whole-genome (n = 184) and exome (n = 208) sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline mutations in candidate genes (n = 130) with established predisposition to PC or medium-high penetrance genes with well-defined cancer associated syndromes or phenotypes. Variants from candidate genes were annotated and classified according to international guidelines. Variants were considered actionable if clinical utility was established, with regard to prevention, diagnosis, prognostication and/or therapy. RESULTS: A total of 48,904 germline variants were identified, with 2356 unique variants undergoing annotation and in silico classification. Twenty cases were deemed actionable and were returned via previously described RoR framework, representing an actionable finding rate of 5.1%. Overall, 1.78% of our cohort experienced clinical benefit from RoR. CONCLUSION: Returning research results within the context of large-scale genomics research is a labour-intensive, highly variable, complex operation. Results that warrant action are not infrequent, but the prevalence of those who experience a clinical difference as a result of returning individual results is currently low.

10 Article Upstream and Downstream Co-inhibition of Mitogen-Activated Protein Kinase and PI3K/Akt/mTOR Pathways in Pancreatic Ductal Adenocarcinoma. 2016

Wong, Matthew H / Xue, Aiqun / Baxter, Robert C / Pavlakis, Nick / Smith, Ross C. ·Cancer Surgery Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Gosford Hospital, Sydney, NSW, Australia. · Cancer Surgery Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia. · Hormones and Cancer, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia. · Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia. · Cancer Surgery Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia. ·Neoplasia · Pubmed #27435925.

ABSTRACT: BACKGROUND: Extensive cross talk exists between PI3K/Akt/mTOR and mitogen-activated protein kinase (MAPK) pathways, and both are upregulated in pancreatic ductal adenocarcinoma (PDAC). Our previous study suggested that epidermal growth factor receptor inhibitor erlotinib which acts upstream of these pathways acts synergistically with PI3K inhibitors in PDAC. Horizontal combined blockade upstream and downstream of these two pathways is therefore explored. METHODS: Erlotinib paired with PI3K inhibitor (BYL719) was tested against erlotinib plus dual PI3K/mTOR inhibitor BEZ-235, and MEK inhibitor (PD98059) plus BEZ235, on five primary PDAC cell lines and on two pairs of parent and erlotinib-resistant (ER) cell lines. A range of in vitro assays including cell proliferation, Western blotting, migration, clonogenic, cell cycle, and apopotic assays was used to test for the efficacy of combined blockade. RESULTS: Dual downstream blockade of the MAPK and PAM pathways was more effective in attenuating downstream molecular signals. Synergy was demonstrated for erlotinib and BEZ235 and for PD-98059 and BEZ-235. This resulted in a trend of increased growth cell cycle arrest, apoptosis, cell proliferation, and colony and migration suppression. This combination showed more efficacy in cell lines with acquired resistance to erlotinib. CONCLUSIONS: The additional mTOR blockade provided by BEZ235 in combined blockade resulted in increased anticancer effect. The hypersensitivity of ER cell lines to additional mTOR blockade suggested PAM pathway oncogenic dependence via mTOR. Dual downstream combined blockade of MAPK and PAM pathways with MEK and PI3K/mTOR inhibitor appeared most effective and represents an attractive therapeutic strategy against pancreatic cancer and its associated drug resistance.

11 Article Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors. 2015

Mehta, Shreya / de Reuver, Philip R / Gill, Preetjote / Andrici, Juliana / D'Urso, Lisa / Mittal, Anubhav / Pavlakis, Nick / Clarke, Stephen / Samra, Jaswinder S / Gill, Anthony J. ·From Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia (SM, PDR, PG, AM, JSS) · Department of Medical Oncology, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia (NP, SC) · Macquarie University Hospital, Macquarie University, New South Wales, Australia (JSS) · and Department of Anatomical Pathology Royal North Shore Hospital, Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia (JA, LDU, AJG). ·Medicine (Baltimore) · Pubmed #26447992.

ABSTRACT: Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival. This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs. This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed. A total of 99 cases were included in this study. The mean age was 57.8 years (18-87 years) and median tumor size was 25 mm (range 8-160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1-0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1-5.7). Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs.

12 Article Pathogenic PALB2 mutation in metastatic pancreatic adenocarcinoma and neuroendocrine tumour: A case report. 2015

Chan, David / Clarke, Stephen / Gill, Anthony J / Chantrill, Lorraine / Samra, Jas / Li, Bob T / Barnes, Tristan / Nahar, Kazi / Pavlakis, Nick. ·Northern Sydney Cancer Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. · Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. · Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Mol Clin Oncol · Pubmed #26171187.

ABSTRACT: Adenocarcinoma of the pancreas is an aggressive malignancy with poor prognosis. Pancreatic neuroendocrine tumours (PNET) comprise ~3% of primary pancreatic neoplasms and they are more heterogeneous in their histological character and outcome. This is the case report of a 73-year-old female patient with synchronously diagnosed pancreatic adenocarcinoma and PNET, which is likely associated with a pathogenic partner and localizer of breast cancer 2, early onset (PALB2) mutation. The potential pathogenic significance of PALB2 and its association with various malignancies were investigated and the potential role of PALB2 in conferring sensitivity to chemotherapeutic agents, such as mitomycin C and cisplatin, was discussed. This case report highlights the significance of ongoing research into the molecular pathogenesis of pancreatic cancer, which may help guide the selection of optimal treatments for this disease, as well as the need for ongoing study of PALB2 as a possible predictive marker of response to DNA-damaging agents.

13 Article Cotargeting of epidermal growth factor receptor and PI3K overcomes PI3K-Akt oncogenic dependence in pancreatic ductal adenocarcinoma. 2014

Wong, Matthew H / Xue, Aiqun / Julovi, Sohel M / Pavlakis, Nick / Samra, Jaswinder S / Hugh, Thomas J / Gill, Anthony J / Peters, Lyndsay / Baxter, Robert C / Smith, Ross C. ·Cancer Surgery; Medical Oncology. · Cancer Surgery; · Medical Oncology. · Upper Gastrointestinal Surgery, and. · Pathology, Royal North Shore Hospital, Sydney, Australia. · Flow Cytometry Unit, Haematology Division; · Hormones and Cancer Division, Kolling Institute of Medical Research, University of Sydney; Departments of. · Cancer Surgery; Upper Gastrointestinal Surgery, and ross.smith@sydney.edu.au. ·Clin Cancer Res · Pubmed #24895459.

ABSTRACT: PURPOSE: PI3K-Akt is overexpressed in 50% to 70% of pancreatic ductal adenocarcinoma (PDAC). The hypothesis of this study is that PI3K and EGFR coinhibition may be effective in PDAC with upregulated PI3K-Akt signaling. EXPERIMENTAL DESIGN: Multiple inhibitors were tested on five PDAC cell lines. EGFR inhibitor (EGFRi)-resistant cell lines were found to have significantly overexpressed AKT2 gene, total Akt, and pAkt. In vitro erlotinib-resistant (ER) cell models (BxPC-ER and PANC-ER) with highly constitutively active PI3K-Akt were developed. These and their respective parent cell lines were tested for sensitivity to erlotinib, IGFIR inhibitor NVP-AEW541 (AEW), and PI3K-alpha inhibitor NVP-BYL719 (BYL), alone or in combination, by RTK-phosphoarray, Western blotting, immunofluorescence, qRT-PCR, cell proliferation, cell cycle, clonogenic, apoptosis, and migration assays. Erlotinib plus BYL was tested in vivo. RESULTS: Erlotinib acted synergistically with BYL in BxPC-ER (synergy index, SI = 1.71) and PANC-ER (SI = 1.44). Treatment of ER cell lines showing upregulated PI3K-Akt with erlotinib plus BYL caused significant G1 cell-cycle arrest (71%, P < 0.001; 58%, P = 0.003), inhibition of colony formation (69% and 72%, both P < 0.001), and necrosis and apoptosis (75% and 53%, both P < 0.001), more so compared with parent cell lines. In primary patient-derived tumor subrenal capsule (n = 90) and subcutaneous (n = 22) xenografts, erlotinib plus BYL significantly reduced tumor volume (P = 0.005). Strong pEGFR and pAkt immunostaining (2+/3+) was correlated with high and low responses, respectively, to both erlotinib and erlotinib plus BYL. CONCLUSION: PDAC with increased expression of the PI3K-Akt pathway was susceptible to PI3K-EGFR coinhibition, suggesting oncogenic dependence. Erlotinib plus BYL should be considered for a clinical study in PDAC; further evaluation of pEGFR and pAkt expression as potential positive and negative predictive biomarkers is warranted.

14 Article Adverse tumor biology associated with mesenterico-portal vein resection influences survival in patients with pancreatic ductal adenocarcinoma. 2014

Wang, F / Gill, A J / Neale, M / Puttaswamy, V / Gananadha, S / Pavlakis, N / Clarke, S / Hugh, T J / Samra, J S. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, St Leonards, NSW, Australia, fwang1881@gmail.com. ·Ann Surg Oncol · Pubmed #24558067.

ABSTRACT: BACKGROUND: Although pancreatoduodenectomy (PD) with mesenterico-portal vein resection (VR) can be performed safely in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the impact of this approach on long-term survival is controversial. PATIENTS AND METHODS: Analyses of a prospectively collected database revealed 122 consecutive patients with PDAC who underwent PD with (PD+VR) or without (PD-VR) VR between January 2004 and May 2012. Clinical data, operative results, and survival outcomes were analysed. RESULTS: Sixty-four (53 %) patients underwent PD+VR. The majority (84 %) of the venous reconstructions were performed with a primary end-to-end anastomosis. Demographic and postoperative outcomes were similar between the two groups. American Society of Anesthesiologists (ASA) score, duration of operation, intraoperative blood loss, and blood transfusion requirement were significantly greater in the PD+VR group compared with the PD-VR group. Furthermore, the tumor size was larger, and the rates of periuncinate neural invasion and positive resection margin were higher in the PD+VR group compared with the PD-VR group. Histological venous involvement occurred in 47 of 62 (76 %) patients in the PD+VR group. At a median follow-up of 29 months, the median overall survival (OS) was 18 months for the PD+VR group, and 31 months for the PD-VR group (p = 0.016). ASA score, lymph node metastasis, neurovascular invasion, and tumor differentiation were predictive of survival. The need for VR in itself was not prognostic of survival. CONCLUSIONS: PD with VR has similar morbidity but worse OS compared with a PD-VR. Although VR is not predictive of survival, tumors requiring a PD+VR have more adverse biological features.

15 Article Diagnostic Accuracy of Imaging Modalities in the Evaluation of Vascular Invasion in Pancreatic Adenocarcinoma: A Meta-Analysis. 2013

Li, Angela E / Li, Bob T / Ng, Bernard H K / McCormack, Sam / Vedelago, John / Clarke, Stephen / Pavlakis, Nick / Samra, Jaswinder. ·Department of Radiology, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia. · Department of Medical Oncology, Royal North Shore Hospital, St Leonards NSW 2065, Australia. · Sydney Medical School, University of Sydney, Camperdown NSW 2050, Australia. · Imaging Partners Online, Sydney NSW 2000, Australia. · Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards NSW 2065, Australia. ·World J Oncol · Pubmed #29147335.

ABSTRACT: Background: The extent of vascular invasion is a key factor determining the resectability of non-metastatic pancreatic adenocarcinoma. The purpose of this study is to determine the diagnostic accuracy of computed tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance imaging (MRI) in the pre-operative evaluation of vascular invasion in pancreatic adenocarcinoma, with surgery as the reference standard. Methods: A search of the MEDLINE database for relevant articles in the English language published between January 2000 and February 2009 was performed. From each study, 2 × 2 tables were obtained, and pooled sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and diagnostic odds ratios were calculated for each modality, along with a summary receiver operating characteristics (SROC) curve. Results: 16 studies with a total of 797 patients who had surgical assessment of vascular invasion were included in the analysis. Several studies evaluated more than one imaging modality, allowing 24 datasets to be obtained in total. Sensitivity was highest for CT (0.73, 95% CI 0.67 - 0.79), followed by EUS (0.66, 95% CI 0.56 - 0.75) and MRI (0.63, 95% CI 0.48 - 0.77). The specificity for all three imaging modalities was comparable. The diagnostic odds ratios for CT, EUS and MRI were 45.9 (95% CI 18.0 - 117.4), 23.0 (95%CI 9.4 - 56.6), 23.9 (95% CI 5.4 - 105.1) respectively. Conclusion: CT was more accurate than EUS and MRI in the evaluation of vascular invasion in pancreatic adenocarcinoma and should be the first line investigation in pre-operative staging.