AGITG 2019 Annual Scientific Meeting Highlights of Interest to Translational Scientists

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

INVITED FACULTY MEMBERS OF INTEREST TO SCIENTISTS INCLUDE:

Professor Christian Jobin – University of Florida, Gainesville, United States of America

Professor Christian Jobin is the Gatorade Trust Professor of Medicine at the University of Florida Gainesville.  He received his PhD in Immunology/Microbiology from Université Laval (Quebec, Canada) in 1994.  He did a post-doctoral fellowship at the University of North Carolina Chapel Hill working on bacteria host interaction in the intestine.  Dr. Jobin’s research focuses on establishing the functional impact of bacteria in inflammation and carcinogenesis and deciphering mechanism of action.  Using genetically engineered mice and zebrafish, germ-free and gnotobiotic technology in combination with microbial genomics, his lab studies the role of bacteria in cancer.  His laboratory showed the key role of genotoxic microbial gene cluster in carcinogenesis.  He has published over 160 scientific papers (Science, Nature, Nat. Comm., Nat. Micro., Immunity, J. Exp. Med., Gastroenterology) and presented his work at various national and international scientific meetings (over 190 conferences).  His research, supported by the National Institute of Health has led to numerous awards and honours (Mucosal Immunology Society Award, American Gastroenterological Association Fiterman Young Investigator Basic Research Award, UF Senior Faculty Excellence in Research Award). Dr. Jobin has served on several study sections including American Cancer Society, CCFA Fellowship and Career Awards, NIH tumor microenvironment and he is currently serving on the Gastrointestinal Mucosal Pathobiology study section (GMPB-permanent member). He is the co-leader of the Cancer Therapeutics Host Response research program at the University of Florida Health Cancer Center.

Professor Emad M. El-Omar – St George Hospital, Sydney, Australia

Professor El-Omar graduated in Medicine from Glasgow University, Scotland, and trained as a gastroenterologist. He worked as a Visiting Scholar/Scientist at Vanderbilt University, TN, and National Cancer Institute, MD, USA, and was Professor of Gastroenterology at Aberdeen University, Scotland, for 16 years before taking up the Chair of Medicine at St George & Sutherland Clinical School, University of New South Wales, Sydney, Australia. He is the Editor in Chief of the journal Gut. His research interests include the gut microbiome, inflammation driven GI cancer and IBD. He is the Director of the Microbiome Research Centre at St George Hospital, Sydney.

MEETING HIGHLIGHTS OF PARTICULAR INTEREST TO SCIENTISTS INCLUDE:

WEDNESDAY 21 AUGUST

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 presentation by:

Professor Christian Jobin – The large fingerprint of Intestinal microbiota in cancer

“The hallmarks of cancer proposed by Hanahan and Weinberg close to 20 years ago has evolved to include biological features such as proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genome instability, energy metabolism, evading immune destruction and tumor-promoting inflammation. Since the vast majority of cancer cases (~90%) are attributed to sporadic events and not hereditary inherited, this cancer hallmarks is likely influenced by environmental conditions. Understanding the contribution of these various environmental factors to this hallmark could provide new means to prevent development of GI cancer such as colorectal, pancreatic and liver cancer, or at least to help manage these pathologies. The most ubiquitous environmental factor, the microbiota, has emerged as an important modulator of carcinogenesis.  In particular, intestinal microbiota appears to impact on cancer hallmarks through a wide array of properties such as genotoxin, immune, and metabolic activities. In this lecture, I will overview key properties by which intestinal bacteria modulate carcinogenesis.” – Professor Christian Jobin.

And presentations from other Invited Faculty:

Associate Professor Manisha Palta – Combination of radiation and immunotherapy: Fact or fiction. Toxicity versus benefit

“There is strong interest and preclinical data supporting the potential synergistic effects of radiation in combination with immunotherapy. Multiple Phase I and Phase II trials are ongoing. There are apparent overlapping toxicities of these modalities such as pneumonitis and colitis, however, can these potential increased risk for toxicities be managed if disease outcomes are enhanced? This talk will focus on the current status of data surrounding radiation with immunotherapy, potential toxicities associated with this treatment, and the potential benefits of this approach.” – Associate Professor Manisha Palta

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

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

Chairs: A/Prof Mustafa Khasraw, Dr Andrew Oar & Dr Iain Thomson

International Faculty Panel: Prof Stephen J Wigmore, Prof Jim Abbruzzese & A/Prof Manisha Palta

National Faculty Panel: Prof Desmond Yip, Dr Hien Li, Prof Jaswinder Samra & Mrs Jan Mumford

This session will commence with:

State of the art management of operable pancreatic tumours – Professor Jim 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 Jim Abbruzzese

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

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: Dr Alexander P. Davis

Radiation Oncology: Dr Sweet Ping Ng

THURSDAY 22 AUGUST

Translational Science Symposiums

Bugs, Drugs and Biologicals in GI Cancer

Co-Chairs: Professor Robert Ramsay and Associate Professor Vicki Whitehall

“GI cancers develop within the complex environment of the patient where there is a relenting battle between the cancer cells and the host. Pioneers like Paget and Virchow recognized that there are roles played by non-tumour cells we now describe as immune, vessel and other stromal cells. More recent appreciation has emerged of another complex population of organisms that imping upon this battle are those of the microbiota; fungi, bacteria and their phages. Together as intact organisms or products they influence tumour growth, responses to cytotoxic drugs and immunotherapeutics. The translational session traverses these topics of microbiota, chemotherapies and immune modulators as they impact GI cancers.” – Professor Robert Ramsay

Microbiota function in cancer initiation and therapeutics

Professor Christian Jobin

“Gene-environment interaction plays a key role in disease susceptibility, including cancer.  Microbiota, an important environmental factor is directly influenced by known cancer risk factors such as lifestyle, diet and inflammation.  An intriguing component of microbiota is its ability to modulate immune response, a critical feature that profoundly impact host homeostasis.  Interestingly, this microbiota property could be beneficial or deleterious to the host, depending on the biological context where these responses take place.  In this lecture, I will present evidence that interaction between bacteria and inflammation is critical for colorectal development, and that therapeutic intervention aimed at blocking inflammation functionally altered microbiota cancer activities.  On the opposite end of the spectrum, I will discuss how microbiota is indispensable for the anti-tumor efficacy of immunotherapy.  These studies will highlight the delicate balance between cancer promoting and cancer therapeutic aspect of the intestinal microbiota on local environment and long-distance organs.  Understanding the far reach impact of microbiota on carcinogenesis (initiation and treatment) will likely identify new potential therapeutic target for cancer management.” – Professor Christian Jobin

The Microbiome in Upper GI Cancer

Professor Emad El-Omar

Translational Science Session continues after Morning Tea with

Cutting Edge Translational Science in GI Cancer

Co-Chairs: Professor Oliver Sieber and Doctor Susan Woods

Six experts present on a topic of their choice followed by Panel discussion:

  • Bench to bedside: engineering bacteria to detect, prevent and treat colorectal cancer – Associate Professor Daniel Worthley
  • Bedside to practice: TNT, NOM, and avoiding surgery for rectal cancer – Associate Professor Tarik Sammour
  • Overcoming our addiction to oncogenes to target oesophageal adenocarcinoma – Dr Nick Clemons
  • Pooled secondary analysis of clinical trials – making the most of the data Doctor Michael Sorich
  • DCLK1 is a novel driver of gastric cancer – Doctor Michael Buchert
  • Targeting the gut microbiota to improve outcomes of cancer immunotherapy treatmentDr Stephen Blake

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: Dr Grace Gard Accepted

Invited Faculty: Professor James 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: Dr 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: Dr Mark McGregor

Invited Faculty: Professor Florian Lordick

Concept 4

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

Presenter: Dr Ivan Ho Shon

Invited Faculty: Professor

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: Dr 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?

James L. Abbruzzese, MD

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.” – James L. Abbruzzese, MD

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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

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:

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

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

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