AGITG 2019 Annual Scientific Meeting Highlights of Interest to Surgery

This year the AGITG Annual Scientific Meeting includes many sessions of interest to Surgeons, outlining the most up-to-date knowledge in Surgery with national and international Invited Faculty.

INVITED FACULTY MEMBERS OF INTEREST TO SURGEONS INCLUDE:

Professor Stephen J Wigmore – Hepatobiliary-Pancreatic Surgical Services and Edinburgh Transplant Unit, Royal Infirmary of Edinburgh, The United Kingdom

Professor Wigmore is an HPB and transplant surgeon who trained at King’s College Hospital School of Medicine. He worked in London for a couple of years before moving to Edinburgh to work with Sir David Carter and Professor James Garden. He undertook his basic and higher surgical training in Edinburgh. In 2005 he was appointed Professor of Transplantation Surgery at the Liver Unit in Birmingham University.

He returned to Edinburgh in 2007 as the Chair of Transplantation Surgery. He is currently the Head of Department of Clinical Surgery at the University of Edinburgh. He is the Surgeon to the Queen in Scotland and is the Chair of the Research Committee of the Royal College of Surgeons of Edinburgh. He is the Honorary Secretary of the James IV Association of Surgeons for the British Isles and Rest of the World Section. He is President of the British Transplantation Society and was elected a Fellow of the Royal Society of Edinburgh.

Ms Kate Furness – Monash Medical Centre, Melbourne, Australia

Kate is a Senior Clinical Dietitian at Monash Medical Centre specialising in oncological upper gastrointestinal and hepatobiliary surgery. Her passion is to provide the best quality, timely and evidence based nutrition support in the pre- and post-operative phases of major surgeries. This has led to the commencement of her PhD with Monash University. As the research dietitian on the randomised controlled trial “Effect of early and intensive nutrition care, delivered via telephone or mobile application, on quality of life in people with upper gastrointestinal cancer”, Kate’s doctoral research looks at a process and mechanisms of action evaluation to determine the core active ingredients that will enable the sustained implementation of a best practice nutrition intervention across broader settings, to improve the quality of life and nutrition status of individuals with upper gastrointestinal cancer.

Kate is also an Associate Investigator on a multicentre randomised controlled trial “Real-time patient-reported outcomes (PROs) in clinical practice – a novel approach to improving quality of care for patients with upper gastrointestinal cancer”.

MEETING HIGHLIGHTS OF PARTICULAR INTEREST TO SURGEONS INCLUDE:

WEDNESDAY 21 AUGUST

Keynote Breakfast Session: Colorectal cancer is one disease but with many faces!

Co-Chairs: Dr Sharon Pattison and Dr Hui Li Wong

Presenter: Professor Sharlene Gill

“Significant advances have been achieved in the systemic and locoregional management of metastatic colorectal cancer (mCRC).  While the heterogeneity of colorectal cancer is recognized, the application in clinical practice is an active work in progress.  Currently, clinically actionable prognostic and predictive biomarker in the management of mCRC include MMR status, RAS/BRAF status and, primary tumour location.  In this presentation, the evidence supporting current and future biomarkers will be reviewed, with a discussion on opportunities for molecular stratification which may inform clinical trial design, as well as potential predictive biomarkers for immunotherapy in mCRC.

This practical session will provide up-to-date information and guidance with an opportunity for questions-and-answers. The aim is to enable participants to understand clinical and research challenges in the management of colorectal cancer– Professor Sharlene Gill

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Opening Plenary: Rare cancers, how can we do better?

Co-Chairs: Professor Tim Price & Doctor Lorraine Chantrill

“For too long we have been making small incremental improvements in outcomes for rare gastrointestinal cancers using chemotherapy.  Are there other more biologically intelligent treatments we could be using in this space? Our Opening Plenary will explore cutting edge therapies for these cancers.” – Doctor Lorraine Chantrill

Featuring multidisciplinary presentations by:

Professor Stephen J WigmoreState of the art treatment for biliary tract cancers

“Cholangiocarcinoma is increasing in incidence in Europe and is now a more common cause of cancer death than hepatocellular carcinoma. Biliary tract cancers are rare and difficult to treat often presenting at an advanced stage and being broadly resistant to chemotherapy. In this paper I discuss the challenges that biliary tract cancers present to surgeons and oncologists.  I will discuss modern scientific approaches to identify novel therapeutic targets in cholangiocarcinoma and I will explore the role of the tumour-stromal environment in cancer growth and how this axis may be a potential target for new treatment strategies for cholangiocarcinoma. In addition, I will consider what may be learned form primary sclerosing cholangitis and biliary fluke infection as inflammatory models of cholngiocarcinoma.

I will discuss the results of the BILCAP and ABC06 trials and discuss the design of a new UK –based trial to evaluate the role of neoadjuvant therapy for hilar and perihilar cholangiocarcinoma. Data on the role of liver transplantation for cholangiocarcinoma will be presented and where such treatment might sit within a multimodal approach to this disease. Treatment approaches for gall bladder cancer and the management of incidental gall bladder cancer will be presented.” – Professor Stephen J Wigmore

Associate Professor Manisha PaltaCombination of radiation and immunotherapy: Fact or fiction. Toxicity versus benefit

Professor Christian JobinThe large fingerprint of Intestinal microbiota in cancer

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AGITG Early Colorectal Trials Session

  • Associate Professor Michael Jameson SPAR, A randomised, placebo-controlled phase II trial of Simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer
  • Doctor Mark Jeffery ASCOLT, Aspirin for DukesC and High-Risk Dukes B Colorectal Cancers. An International, Multi-centre, Double-Blind, Randomised Placebo Controlled Phase III Trial. Presented with ASCOLT Translational Research
  • Professor Chris Karapetis RENO, Prospective Study of “Watch and Wait” Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent chemo-radiotherapy: RENO (Rectal Cancer No Operation)
  • Doctor Christina Teng OXTOX, Can Oxaliplatin dose reduction and neurotoxicity be reduced with ibudilast in people with metastatic colorectal cancer – a phase II randomised study

Following the early colorectal trial updates Professor Sharlene Gill will discuss the AGITG portfolio – and how it fits into the international context.

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AGITG Colorectal Trials Session

  • Associate Professor Niall Tebbutt MODULATE, Modulation of the tumour microinviroment using either vascular disrupting agents or STAT3 inhibition in order to synergise with PD1 inhibition in microsatilite stable, refactory colorectal cancer
  • Associate Professor Niall Tebbutt LIBERATE, A study evaluating liquid biopsies to profile metastatic colorectal cancer
  • Doctor Matthew Burge MONARCC, A randomised phase 2 study of panitumumab monotherapy and panitumumab plus 5 fluorouracil as first line therapy for RAS and BRAF wild type metastatic colorectal cancer
  • Associate Professor Jeanne Tie DYNAMIC-Rectal, circulating tumour DNA Analysis Informing AdjuvantChemotherapy in Locally Advanced Rectal Cancer: A Multicentre Randomised Study

Presented with DYNAMIC-III, Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage III Colon Cancer: A Multicentre Randomised Study.

Following the colorectal trial updates Professor Florian Lordick will discuss the AGITG portfolio – and how it fits into the international context.

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Multidisciplinary Workshop: The Neoadjuvant Approach In Operable Tumours & Other Controversies In Pancreatic Cancer

Chairs: Associate Professor Mustafa Khasraw, Doctor Andrew Oar & Doctor Iain Thomson

International Faculty Panel: Professor Stephen J Wigmore, Professor James L. Abbruzzese & Associate Professor Manisha Palta

National Faculty Panel: Professor Desmond Yip, Doctor Hien Li, Professor Jaswinder Samra & Mrs Jan Mumford

This session will commence with presentations:

Pros of primary surgery in pancreatic cancer – Professor Stephen J Wigmore

“Pancreatic cancer is increasingly been considered as an oncological emergency. This widely adopted mantra has been used as a justification for promoting the role of early surgery in patients with pancreatic ductal adenocarcinoma. Surgical resection is known to offer the only real chance of curing PDAC and up until recently many patients and clinicians believed that the sooner that surgery can be undertaken the better.

In patients presenting with obstructive jaundice, the recognition that proceeding directly to resectional surgery was associated with higher resection rates and fewer complications than for patients in whom a biliary stenting, recovery and then surgery approach was taken, has further fueled the argument for early surgery. Further, recent studies looking at the role of emergency jaundice clinics have shown that early identification of patients with PDAC can permit on average a 4 week reduction in the work up time to get patients to surgery and argue that this may reduce stage migration and reduce the rate of local advancement of disease.

Counter arguments to early surgery centre around the fact that tumour biology and stage ultimately determine outcome irrespective of treatment approach and that tumour stage is often underestimated in pancreas cancer. Early surgery may still have a role in patients who do not want or are not able to tolerate neoadjuvant strategies.” – Professor Stephen J Wigmore

Pros of neoadjuvant therapy in pancreatic cancer – Associate Professor Manisha Palta

“The historic approach of upfront surgical resection and adjuvant therapy has resulted in a 5-year survival of nearly 20%. Recent data incorporating adjuvant FOLFIRINOX has demonstrated a dramatic impact on survival outcomes. Given that nearly a third of patients will not receive the intended adjuvant therapy and the high rates of distant metastatic progression, there is renewed interest in neoadjuvant therapy prior to surgical resection. This approach provides a patient and tumor specific testing of biology to ensure that patients selected from surgery are most likely to benefit from a planned operation. Trials evaluating neoadjuvant therapy are ongoing in an effort to clarify the potential benefit of this treatment paradigm.” – Associate Professor Manisha Palta

State of the art management of operable pancreatic tumours – Professor James L. Abbruzzese

“Pancreatic ductal adenocarcinoma (PDAC) remains an extremely challenging disease. While the incidence is overall low this cancer is highly lethal with greater than 90% of patients dying of advancing disease despite aggressive surgery, radiation therapy and systemic chemotherapy. While most patients diagnosed with pancreatic cancer present with locally advanced (non-operable) or metastatic disease approximately 40-50% of patients will present with localized potentially operable pancreatic cancer. Approximately, 20% of potentially operable PDAC will be defined as “resectable” based on the absence of arterial involvement and limited (≤180%) contact with the portal or superior mesenteric veins without vein contour irregularity or thrombosis. Another 30% of potentially operable patients will present with “borderline resectable” PDAC defined by the extent of arterial and/or venous involvement.

As the multidisciplinary management of potentially operable PDAC has evolved there is reasonable consensus that to achieve negative surgical margins multimodality neo-adjuvant therapy consisting of chemotherapy (typically FOLFIRINOX or gemcitabine + nab-paclitaxel) and based on some studies radiotherapy or chemoradiation therapy should be administered with periodic re-imaging to reconfirm operability prior to surgical intervention.

The greatest area of uncertainty (lack of equipoise) exists with respect to the management of potentially resectable PDAC and this presentation will review some of the studies that contribute to this uncertainty. Well-designed trials examining neo-adjuvant vs. adjuvant strategies are being developed and will help to understand if one approach is superior.” – Professor James L. Abbruzzese

Effect of early and intensive nutrition care, delivered via telephone or mobile application, on quality of life in people with upper gastrointestinal cancer – Ms Kate Furness

“Cost-effective ways to deliver nutrition care sooner to people with upper gastrointestinal cancer are needed urgently. People with upper gastrointestinal cancer often develop malnutrition and this confers greater risks of morbidity and mortality. The aim of this study is to investigate if nutrition intervention, delivered by a dietitian using e-health from the time of diagnosis can improve quality of life compared with usual in-hospital referral based dietetic services.   This study is a three-group randomised controlled trial, with a concurrent economic evaluation. Participants (n=111) had a new primary diagnosis of gastric, oesophageal or pancreatic cancer and planned treatment of chemo/radiotherapy and/or surgery.  They were randomised to either usual care (control group) or to one of two intervention groups to receive an enhanced nutrition intervention for 18 weeks in addition to usual care services either via telephone (group 1), or via a mobile app (group 2). The intervention is an individually tailored, symptom-directed nutritional behavioural management program led by a dietitian. The primary outcome is quality-adjusted life years lived, assessed at three, six and 12 months follow up. Secondary outcomes include markers of nutritional status. Process measures are assessed to inform future implementation in other settings. This patient-centred approach to nutrition care is relevant to current health service provision and challenges the current reactive delivery model of care.” – Ms Kate Furness

This will be followed by brief case presentations:

Medical Oncology: Doctor Alexander P. Davis

Radiation Oncology: Doctor Sweet Ping Ng

THURSDAY 22 AUGUST

Keynote Breakfast Session: The role of SBRT in oligometastatic gastro-intestinal cancer

Presenter: Associate Professor Manisha Palta

Co-Chairs: Doctor Andrew Oar & Doctor Dominique Lee

“Traditional palliative approaches to patients with early metastatic disease has been an area of active research.  Recent randomised evidence has demonstrated an overall survival benefit for SBRT in oligometastatic disease in non-small cell lung cancer.  To date, no randomised trials have been published exploring SBRT in oligometastatic gastrointestinal cancer. This keynote session will discuss the “Who”, “When” and “Why” of SBRT in oligometastatic gastrointestinal cancers and the opportunity for meaningful research in this controversial domain.” – Doctor Andrew Oar

New Concepts Symposium

Co-Chairs:  Professor Tim Price Accepted & Doctor Katrin Sjoquist

Four concepts will be presented with opportunity for audience feedback. International Faculty will provide comments in terms of perspective, relevance and international interest.

Concept 1

A randomised phase II study to define the feasibility of organoid sensitivity testing driven treatment for patients with chemorefractory metastatic colorectal cancer

Presenter: Doctor Grace Gard Accepted

Invited Faculty Reviewer: Professor James L. Abbruzzese

Concept 2

Phase 1 study of AqB050 with/without AqB013 in patients with metastatic colorectal cancer following progression on standard chemotherapy and biological therapy

Presenter: Doctor Yoko Tomita

Invited Faculty: Professor Christian Jobin

Concept 3

A phase 2 study of oncolytic immunotherapy of metastatic neuroendocrine tumours using intralesional rose bengal disodium in combination with pembrolizumab

Presenter: Doctor Mark McGregor

Invited Faculty Reviewer: Professor Florian Lordick

Concept 4

Positron emission tomography of cell death for prediction of response to neoadjuvant therapy in rectal and oesophageal carcinoma

Presenter: Doctor Ivan Ho Shon

Invited Faculty Reviewer: Professor Sharlene Gill

Followed by: Best of Posters and Fast Forward

Four posters will be presented in the Best of Posters session and four in the Fast Forward session with opportunity for audience questions.

Best of Posters Session

Co-Chairs: Professor Stephen Clarke and Professor Robert Ramsay

1. Palliative Oesophageal Chemoradiotherapy: A Phase I Clinical Trial

Presenter: Doctor Fiona Day

2. Immunomodulatory effect of Renin-angiotensin inhibitors on T-lymphocytes in mice with Colorectal Liver Metastases

Presenter: Doctor Dora Ardila

3. A comprehensive patient-reported outcome (PRO) assessment model for colorectal cancer (CRC) survivors: a mixed methods systematic review

Presenter: Doctor Claudia Rutherford

4. SPARC expression in pretreatment rectal cancer biopsies is associated with tumour regression following neoadjuvant chemoradiotherapy

Presenter: Associate Professor Christine Hemmings

Fast Forward Session

Co-Chairs: Professor Stephen Clarke and Professor Robert Ramsay

1. Neoadjuvant capecitabine versus infusional 5-fluorouracil for the treatment of locally advanced rectal cancer

Presenter: Doctor Matthew Loft

2. Phase I trial of nab-paclitaxel administered concurrently with radiotherapy in patients with locally advanced inoperable pancreatic adenocarcinoma (ART in LAP trial)

Presenter: Doctor Amitesh Roy

3. Investigating the role of tumour-associated T cells in human colorectal cancer liver metastases

Presenter: Doctor Kevin Fenix

4. The effect of oversewing double stapled anastomoses in oncological colorectal surgery

Presenter: Doctor Simon Wilkins

FRIDAY 23 AUGUST

Keynote Breakfast Session: Translating Perioperative Management of Pancreatic Cancer into Survival Benefits – What new approaches are needed?

Presenter: Professor James L. Abbruzzese

Co-Chairs: Associate Professor Mustafa Khasraw & Dr Melissa Eastgate

“Pancreatic ductal adenocarcinoma (PDAC) remains an extremely challenging disease. While the incidence is overall low this cancer is highly lethal with greater than 90% of patients dying of advancing disease despite aggressive surgery, radiation therapy and systemic chemotherapy. Management of operable pancreatic cancer currently relies on careful staging to assess the vascular relationships surrounding the cancer. Borderline resectable disease is generally managed with preoperative chemotherapy +/- chemoradiation in an effort to improve margin-negative resection rates. For resectable cancers there is equipoise regarding pre-operative vs. post-operative management strategies.

While work continues to refine the sequencing of modalities with surgery it is also clear that the greatest impact for patients will be to understand the rising incidence of PDAC and develop strategies to reduce the incidence of pancreatic cancer, identify patients at high risk, improve early detection strategies and develop more effective therapies for the management of metastatic disease.  Such improvements will occur through precision medicine strategies, understanding the cross-talk between cancer cells and the microenvironment, and harnessing the therapeutic power of the immune system. This presentation will briefly cover each of these emerging areas of research.” – Professor James L. Abbruzzese

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AGITG Upper GI Cancer Trials Session

  • Professor Desmond YipALT-GIST, A randomised Phase II trial of imatinib alternating with regorafenib compared to imatinib alone for the first line treatment of advanced gastrointestinal stromal tumour (GIST)
  • Professor Andrew Barbour DOCTOR, A Randomised Phase II trial of pre-operative cisplatin, 5 fluorouracil anddocetaxel, +/- Radiotherapy, based on poor early response to standard chemotherapy for resectable adenocarcinoma of the oesophagus and/or gastro oesophageal junction. Presented with DOCTOR Translational Research
  • Professor Trevor Leong TOP GEAR, A randomised II/III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer
  • Doctor Belinda Lee – DYNAMIC-Pancreas, Circulating tumour DNA Analysis Informing Adjuvant Chemotherapy in Early Stage Pancreatic Cancer: A Multicentre Randomised Study
  • Doctor Jenny Shannon ACTICCA-1, Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gall bladder carcinoma
  • Doctor David WyldCONTROL NETS, Capecitabine ON Temozolomide Radionuclide therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
  • Associate Professor Mustafa Khasraw – NABNEC, A Randomised Phase II Study Of nab-paclitaxel in Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas
  • Doctor Andrew Oar – MASTERPLAN, A randomised phase II study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease

 Following the Upper GI Cancer trial updates Professor James Abbruzzese will discuss the AGITG portfolio – and how it fits into the international context.

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Closing Plenary: Trials and Tribulations in Colorectal cancer in 2019

Co-Chairs: Associate Professor Michael Jameson and Professor Stephen Ackland

“New treatments for colorectal cancer have been sparse in the past few years.  Are there ways we could look at this diverse group of bowel cancers? Our closing plenary will look at colorectal cancer through different lenses” – Dr Lorraine Chantrill

Including International Expert Panel: Professor Florian Lordick Professor Christian Jobin, Associate Professor Manisha Palta and Professor Stephen Wigmore

Presentation by Professor John Simes – 2018 recipient of the John Zalcberg OAM Award for Excellence in AGITG Research

Presentations by:

Hottest Topic in Colorectal Cancer – Biomarker-Guided Therapy of Chemorefractory CRC – Professor Florian Lordick

“Sequential use of systemic chemotherapy, combined with either anti-EGFR-directed or with VEGF-inhibiting antibodies, has led to dramatically increased survival duration for patients with metastatic colorectal cancer (mCRC). Nevertheless, cure can still not be achieved with medical treatment alone but requires complete surgical resection of the primary tumour and all metastatic sites. In addition, resistance against chemotherapy occurs almost inevitably in the course of medical treatment and patients are in urgent need for more effective treatment options beyond classical cytotoxic drugs.

After a period of stagnation, the number of molecularly stratified treatment options available to patients with mCRC is finally increasing, with a parallel rise in the use of biomarkers to guide prognostication and treatment decision-making. The increase in both the number and use of biomarkers has resulted in a progressively complex situation. Current and emerging biomarkers also reflect the genomic complexity of CRC, and include a wide range of aberrations such as point mutations, amplifications, fusions and hypermutator phenotypes, in addition to global gene expression subtypes. In this talk I will provide an overview of current use of emerging clinically relevant biomarkers and their role in the management of patients with CRC, illustrating the growing treatment opportunities created by the availability of comprehensive molecular profiling.

Recently presented data on molecularly stratified treatment of BRAF and RAS mutated, HER2 amplified, fusion positive and potentially immunotherapy-sensitive mCRC will be reviewed and put into the context of current treatment algorithms.” – Professor Florian Lordick.

Next challenges in moving from microbiome into clinical integration (opportunities and barriers) – Professor Christian Jobin

“A number of studies using preclinical models in conjunction with emerging new evidence generate from clinical trials suggest a potential therapeutic application of microbiota.  This is especially true in the case of recurrent Clostridium difficile infection where patients receiving fecal microbiota transplant achieve high therapeutic outcome.  However, when FMT strategy is applied to other diseases such as IBD, the therapeutic efficacy is less impactful.  This highlights the complexity of harnessing the microbiome for therapeutic purposes in complex disease system.  It is clear that a deeper look into how microbiota interact with the host at the metabolic, cellular and molecular levels would be needed before optimal therapeutic modalities could be generated.  In this lecture, I will present opportunities by which microbiome could be utilized for therapeutic purpose, as well as identify critical road block which would need to be overcome in order to attain the full potential of microbiota in medicine.” – Professor Christian Jobin.

Registry Trials in CRC and other GI Cancers – Professor Peter Gibbs

“Clinical registries have traditionally been used to support the collection of a standard set of patient, treatment and outcome data, to be used for audit and for research purposes. Given the resource intensive nature of cancer registry data collection ensuring useful output should be a high priority, whereas recent analyses have concluded that overall the output from cancer registries to date has been limited. Further, the significant potential for misleading conclusions to be reached has also recently been highlighted, the result of the many confounders that inevitably impact both treatment selection and treatment outcomes, many of which are challenging to capture.  A registry randomised controlled trial (rRCT) is a new concept where the essential patient, treatment and outcome data for the study are collected in a registry rather than standard case report forms. rRCTs promise to increase the impact of registry data collection and through randomization to minimize the impact of confounders. rRCTs can potentially address many of the current knowledge gaps that relate to optimal treatment selection or optimal treatment sequencing in scenarios where more than one active treatment is available. rRCTs can also be used to define optimal treatment duration. Importantly, even sites with limited or no research infrastructure can potentially enroll patients, in comparison to traditional study conduct the cost of running trials is markedly reduced and due to intentionally inclusive entry criteria the external validity of any study conclusions is high.” – Professor Peter Gibbs.