Challenging the enigmatic nature of gastro-intestinal cancers
The 2019 Annual Scientific Meeting (ASM) of Australasian Gastro-Intestinal Trials Group (AGITG) convened by Dr Lorraine Chantrill, Medical Oncologist, was themed ‘Challenging the enigmatic nature of gastro-intestinal cancers’, with a focus on rare and underfunded cancers and cancer subtypes. Dr Chantrill, Head of Medical Oncology at Illawarra Cancer Care Centre, Wollongong Hospital noted, “This meeting is a unique and valuable opportunity for clinicians and researchers working in the field of gastro-intestinal cancers to share experiences and insights. It is through this networking and collaboration that we can generate better treatments for these cancers.”
Dedicated Trainee and Study Coordinator Workshops were held the day before the ASM, focused on providing a compelling education program for the relevant discipline, covering a wide range of topics presented by highly regarded experts in the field, in addition to a forum to foster collaboration.
In the Trainee Workshop, statistician Rebecca Asher spoke about the ‘role of statistics in producing a well-designed trial with high quality results’, specifically statistical concepts for consideration in trial development and reporting of results. Presentations that followed included Flynn Slattery’s guide to ‘creating an effective scientific poster’, ‘protocol writing’ by Prof Chris Karapetis, with the final session led by Dr Amitesh Roy, Dr Lorraine Chantrill and Prof David Watson on ‘key issues and challenges in designing and conducting clinical trials’ in the rapidly changing landscape of GI cancer.
The Study Coordinator Workshop commenced with a highly interactive presentation from Tanya Symons on important Good Clinical Practice topics such as safety reporting, serious breach of GCP/protocol and risk-based monitoring. Dr Matthew Burge followed with a fascinating talk about the ‘pathology and biology of GI cancer, current treatment and biomarkers that influence clinical practice’. Flynn Slattery represented the poster creation methods in this setting after lunch, followed by engaging topics ‘challenges of current site governance mechanisms’ and ‘translating research into practice’ by Prof Nik Zeps and Prof John Simes, respectively.
Concurrent to the Workshops, a meeting of the AGITG Consumer Advisory Panel (CAP) was held with presentations from Kate Wilson on the ‘competitive grants process’ and an ‘overview of QoL instruments, data collection and results published in AGITG trials’. Dr Katrin Sjoquist presented on ‘RECIST Criteria’ and CAP member Julie Marker presented on ‘peripheral neuropathy’. The CAP also reviewed two new study concepts: the ‘LuCaT’ trial presented by A/Prof Michael Michael and the ‘RANDOMS’ sub-study presented by Katie Benton and Belinda Steer.
The Trainee and Study Coordinator Workshops and CAP Meeting were followed by a tour of the South Australian Health & Medical Research Institute with a lecture on ‘translational research’ presented by Dr Susan Woods and A/Prof Dan Worthley.
We were honoured to host a large complement of Australian and International experts, including:
- Prof James L. Abbruzzese, Medical Oncologist (Duke Cancer Institute, USA)
- Prof Sharlene Gill, Medical Oncologist (BC Cancer, Canada)
- Prof Christian Jobin, Immunologist/Microbiologist (The University of Florida, USA)
- Prof Florian Lordick, Medical Oncologist (University Hospital Leipzig, Germany)
- A/Prof Manisha Palta, Radiation Oncologist (Duke University School of Medicine, USA)
- Prof Stephen J. Wigmore, Surgeon (Royal Infirmary of Edinburgh, UK)
- Ms Kate Furness, Clinical Dietitian (Monash Medical Centre, VIC)
- A/Prof Eddie Lau, Radiologist & Nuclear Medicine Specialist (Austin Health, VIC)
- Prof Emad El-Omar, Gastroenterologist (St George Hospital, NSW)
- Prof Peter Gibbs, Medical Oncologist (University of Melbourne, VIC)
- Ms Tanya Symons, Clinical Research Consultant (Symons Associates, NSW)
The ASM began with the keynote breakfast session, where Prof Gill presented, ‘Colorectal cancer is one disease but with many faces’; a review of the evidence supporting current and future biomarkers for metastatic colorectal cancer (mCRC) and opportunities for molecular stratification, that may inform clinical trial design, as well as potential predictive biomarkers for immunotherapy in this disease area. Colorectal cancers respond differently to treatment depending on their subtype, notably RAS, tumour sidedness, MMR status and BRAF – but there is scope to be more selective. The challenges for treating colorectal cancer in the future include the limited success for basket trials for metastatic colorectal cancer, and adapting clinical trials to the changing landscape.
At the opening Plenary entitled ‘Rare cancers: How can we do better?’ Prof Jobin spoke about the predictive power of microbiota. There is some evidence that the tumour microbiome can predict pancreatic cancer patients’ outcomes, and that microbiota diversity could have an impact on treatment for some cancers. Prof Wigmore spoke about state of the art treatment for biliary cancers, outlining the effectiveness of current surgical approaches and therapies, and research into novel drug targets.
Finally, A/Prof Palta gave a presentation on the combination of radiation and immunotherapy, weighing up toxicity and benefit. There is evidence that immunotherapy prior to radiotherapy may have an impact in some cases, and that there could be an enhancement in effectiveness when treatments are combined. She also shared ongoing phase II data of a neoadjuvant chemoradiation and immunotherapy trial in resectable oesophageal cancer at her centre.
In the afternoon, the Multidisciplinary Workshop provided an opportunity for delegates to delve into controversies in pancreatic cancer. Prof Abbruzzese opened by speaking about the state of the art management of operable pancreatic tumours. Prof Wigmore and A/Prof Palta presented fascinating arguments on the pros and cons of primary surgery versus neoadjuvant therapy. Ms Kate Furness spoke about the effect of early and intensive nutrition care on quality of life for people with upper GI cancers. Finally, national and international panel members from the fields of medical oncology, radiation oncology and surgery, along with the Chair of the AGITG CAP discussed controversies in treating this disease using real cases and treatments.
On Thursday, A/Prof Palta gave a fascinating presentation on treating oligometastatic disease with SBRT. She spoke about the benefits of ablative radiotherapy and noted that higher doses seemed to be more effective. She also talked about all the available data and gaps in knowledge.
This was followed by the Translational Science Symposium, where six experts presented updates on cutting-edge translational science in GI cancer, specifically the microbiome and their ability to influence tumour growth, responses to cytotoxic drugs and immunotherapeutics. Prof Jobin discussed how programmable bacteria may cause tumour regression. Prof El-Omar spoke about how outcomes for upper GI cancers could be affected by changes in the microbiome.
Other highlights of the Translational Science Symposium included Dr Tarik Sammour’s discussion of research regarding TNT followed by surgery for rectal cancer, which improves PCR and DFS. The topic of pooled data analyses was covered by Dr Michael Sorich, providing interesting insights into how secondary data can be acquired from existing trials but could involve time consuming data preparation. Prof John Mariadason discussed IDH, ERBB, FGFR, and MEK mutations found in biliary tract cancers highlighting mixed data when drugs were given against these oncogenes.
The Radiation Oncology Workshop on Thursday was focused on anal cancer treatment. A/Prof Eddie Lau discussed response assessment using PET scans and the role of interim PET, and A/Prof Palta delved into new approaches like the role of dose escalation and individualised radiotherapy for this disease.
At the Joint Consumer / Study Coordinator Forum, a range of topics were discussed, including the importance of quality of life and survivorship research led by Dr Claudia Rutherford, and A/Prof Haryana Dhillon’s discussion of how exercise can affect outcomes for patients. Consumer Advisory Panel member Grant Baker gave insight into the challenges of patient compliance through the lens of his own experience.
One highlight of the ASM each year is the New Concepts Symposium. Four new research concepts were presented with feedback from the International Faculty:
- Best New Concept Award: A phase II study of oncolytic immunotherapy of metastatic neuroendocrine tumours using intralesional rose bengal disodium in combination with pembolizumab, presented by Dr Mark McGregor; and reviewed by Prof Florian Lordick
- Runner-Up Award: A randomised phase II study to define the feasibility of organoid sensitivity testing driven treatment for patients with chemorefractory metastatic colorectal cancer, presented by Dr Grace Gard; and reviewed by Prof James L. Abbruzzese
- A phase I study of AqB050 with/without AqB013 in patients with metastatic colorectal cancer following progression on standard chemotherapy and biological therapy, presented by Dr Yoko Tomita; and reviewed by Prof Christian Jobin
- Positron emission tomography of cell death for prediction of response to neoadjuvant therapy in rectal and oesophageal carcinoma, presented by Dr Ivan Ho Shon; and reviewed by Prof Sharlene Gill
The Best of New Concepts Award is sponsored by Specialised Therapeutics.
Four posters were presented during the Best of the Best Posters Session:
- Best of the Best Posters Award: Palliative Oesophageal Chemoradiotherapy: A Phase I Clinical Trial, presented by Dr Swetha Sridharan;
- Immunomodulatory effect of Renin-angiotensin inhibitors on T-lymphocytes in mice with Colorectal Liver Metastases, presented by Dr Dora Ardila;
- A comprehensive patient-reported outcome (PRO) assessment model for colorectal cancer (CRC) survivors: a mixed methods systematic review, presented by Dr Claudia Rutherford;
- SPARC expression in pretreatment rectal cancer biopsies is associated with tumour regression following neoadjuvant chemoradiotherapy, presented by A/Prof Christine Hemmings.
At the Fast Forward session, delegates had three minutes each to present their concept, and three minutes for questions. The concepts presented were:
- Best Fast Forward Award: The effect of oversewing double stapled anastomoses in oncological colorectal surgery, presented by Dr Simon Wilkins;
- Neoadjuvant capecitabine versus infusional 5-fluorouracil for the treatment of locally advanced rectal cancer, presented by Dr Matthew Loft;
- Phase I trial of nab-paclitaxel administered concurrently with radiotherapy in patients with locally advanced inoperable pancreatic adenocarcinoma (ART in LAP trial), presented by Dr Amitesh Roy;
- Investigating the role of tumour-associated T cells in human colorectal cancer liver metastases, presented by Dr Kevin Fenix
The Best of the Best Posters Award and Best of Fast Forward Award are sponsored by GenesisCare.
At the 21st Annual Meeting Dinner on Thursday night, the AGITG Innovation Fund was awarded to Prof Peter Gibbs for ‘An organoid sensitivity testing driven umbrella study for patients with chemorefractory metastatic colorectal cancer.’
“I am thrilled that we have received the Innovation Fund grant to conduct such an important study,” says Professor Gibbs. “This grant will enable us to test a new development in personalised bowel cancer treatment that could give hope to people who have no other options.”
Prof Val Gebski was recognised for his outstanding contribution to the AGITG with the John Zalcberg OAM Award for Excellence in AGITG Research.
“It is an honour to receive the John Zalcberg OAM Award,” Professor Gebski said. “I am proud to have contributed to research which has resulted in improvements in gastro-intestinal cancer treatment, and to have contributed to the design of high quality clinical trials resulting in international recognition of the excellence of AGITG.”
The Merck-AGITG Kristian Anderson Award was presented to Dr Ryan Cohen. Dr Cohen will complete his PhD at the University of Western Australia. A/Prof Niall Tebbutt received the inaugural AGITG Member Fundraiser of the Year Award in recognition of his commitment to fundraising for GI cancer research, and Calvary Mater Newcastle received the AGITG Outstanding Site Award for its commitment to AGITG clinical trials.
Friday began with the meeting’s final keynote breakfast session presented by Prof Abbruzzese, who discussed translating treatment of pancreatic cancer into survival benefits, including emerging areas of research such as the microenvironment and the disruptive nature of precision medicine. He outlined the evolving understanding of pancreatic cancer including aetiology, and how the development of precision oncology holds promise for the future.
Finally, Prof Tim Price and Prof Stephen Ackland chaired the closing Plenary entitled ‘Trials and tribulations in colorectal cancer in 2019’. Prof John Simes, the 2018 recipient of the John Zalcberg OAM Award for Excellent in AGITG Research, presented on the importance of clinical trials. He noted the benefit to cost ratio of clinical trials, and that well conducted randomised trials are still needed to inform best practice. Innovation Fund recipient Prof Peter Gibbs discussed registry trials in colorectal cancer and other GI cancers. He stated that in improving registry based research it was key to have bigger numbers, better quality, and broader scope.
It was then time to hear insights from the Invited Faculty. Prof Jobin addressed the tremendous clinical translational potential of microbiomes in cancer. Microbiota is an integral component of the host, and there is a link between diet, microbiota and inflammation. Finally, Prof Lordick discussed recent advances and perspectives of stage IV colorectal cancer, including deficient mismatch repair, BRAF mutated, KRAS mutated and HER2 amplified tumours, as well as gene fusion. He stressed the role of doctors as guides and partners of patients over a long period of time.
AGITG trials were also presented in updates across the three days:
- Colorectal and anal cancer trials including updates on SPAR (Prof Stephen Ackland), DYNAMIC-Rectal & DYNAMIC-III (A/Prof Jeanne Tie), ASCOLT (Dr Mark Jeffrey), RENO (Prof Chris Karapetis), MODULATE & LIBERATE (A/Prof Niall Tebbutt), MONARCC (Dr Matthew Burge), InterAACT (Dr Amitesh Roy) and OXTOX (Dr Christina Teng).
- Upper GI, hepatobiliary, GIST and NET cancer trials including INTEGRATE II (A/Prof Nick Pavlakis) ALT-GIST (Prof Desmond Yip) , DOCTOR (Prof Andrew Barbour), TOPGEAR (Prof Trevor Leong), DYNAMIC-Pancreas (Dr Belinda Lee), ACTICCA-1 (Dr Jenny Shannon), CONTROL NETs (A/Prof David Wyld), NABNEC (A/Prof Mustafa Khasraw) and MASTERPLAN (Dr Andrew Oar).
The meeting was an energising experience, thanks to the passion and collaborative atmosphere that was fostered by everyone who attended. It was an example of the dedication of the GI cancer research community, which the AGITG is proud to lead.