Trials, translation and service delivery

Imperial College Experimental Cancer Medicine Centre's main objectives are to develop novel imaging, biomarker and therapeutic approaches that will aid cancer diagnosis and deliver personalised treatment.

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• Experimental Cancer Medicine Centre

The aim of our research is to define the inherited predispositions to colorectal cancer and to refine our management of familial risk in order to prevent familial colorectal cancer. We have a clinical and research database with details of over 3600 individuals from 1500 families under colonoscopic surveillance for familial risk of colorectal cancer with 29,000 patient-years of follow-up. We have been awarded a CRUK infrastructure grant to upgrade the database.

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• Cancer Research UK Imperial Centre (Archived on 8 January 2024 - S Thomas)

Researchers

• Professor Huw Thomas

We aim to foster collaboration, increase synergies, and develop multi-disciplinary projects between pancreatic and liver cancer researchers at Imperial College. The group combines work from the Imperial Pancreatic Cancer Research Group and the Imperial Nanotechnology group on pancreatic cancer.

This initiative facilitates the pooling of knowledge and resources from different departments, and will enable us to expand and build on our successes. We believe that consolidating our strengths – excellence in basic science research and the highest quality clinical care – in this way will improve outcomes for patients. Basic science work is focused on MicroRNAs, circulating tumour cells (CTCs) and liver regeneration. For the first time we described CTCs residing in organs local to pancreatic or colon cancers, and identified 3 mRNAs to differentiate benign from premalignant pancreatic cystic tumours. Currently, a large clinical trial is being proposed to validate these markers and furthermore, a large grant has been sought in conjunction with Nano and Engineering dept on CTC tracking using Tetrahertz technology funded by EPSRC. Professor Long Jiao is the local PI for ESPAC5 trial, a national/international trial on pancreatic cancer.

For surgical innovation, the largest number of laparoscopic liver and pancreatic resection including laparoscopic Whipple’s in the UK currently are performed. In liver surgery, Professor Long Jiao has introduced radiofrequency assisted liver partition with portal vein ligation for staged liver resection (RALPP). Currently, a large RCT is ongoing funded by BRC. In pancreatic surgery, Professor Long Jiao has described longitudinal pancreaticojejunostomy following Whipple’s for pancreatic reconstruction, and laparoscopic Long’s sleeve pancreaticogastrostomy (LPG) for central pancreatectomy.

Trials:

• A first-in-human, multi-centre, open-label, phase 1 clinical study with RNA oligonucleotide drug MTL-CEBPA to investigate its safety and tolerability in patients with advanced liver cancer (outreach)

PI: Mr Duncan Spalding
Sponsor: MiNA Alpha Limited
Funder: Commercially funded

• A phase II multicentre trial of endoscopic ultrasound-guided radiofrequency ablation of cystic tumours of the pancreas

PI: Professor Nagy Habib
Sponsor: University College London
Funder: NIHR

• ESPACS: European Study Group for Pancreatic Cancer - Trial 5F

PI: Professor Long Jiao
Sponsor: University of Liverpool
Funder: Cancer Research UK

Researchers

• Professor Long Jiao (Lead)
• Professor David Blakey (Visiting Professor)
• Dr Leandro Castellano
• Dr Edward Curry
• Mr Adam E. Frampton
• Professor Andrea Frilling
• Professor Nagy Habib
• Professor Norbert Klein
• Dr Jonathan Krell
• Professor Stepan Lucyszyn
• Dr Elaina Maginn
• Professor Stefan Maier
• Mr Madhava Pai
• Professor Pat Price (Visiting Professor)
• Dr Vikash Reebye
• Mr Duncan Spalding
• Professor Molly Stevens
• Dr Harpreet Wasan
• Dr Fang Xie

Translational Molecular Research in Cardiovascular Disease
Our cardiovascular disease research, led by Professor Thanos Athanasiou, focuses on the following areas:

• Metabolomic and MicroRNA profiles in Atrial Fibrillation
• Regenerative and stem cell therapies in cardiovascular disease
• The role of the Toll-like receptor in systemic inflammatory response in cardiac surgery
• Aortic stiffness and biomarkers in aortic valve disease
• Characterization of Cardiac Pluripotent Stem Cells
• Development of cardiac biomaterials for stem cell therapy
• Aortic stiffness and biovalsalva studies utilizing 4D-cardiac MRI and computational modelling technology

Metabolism, Obesity Surgery and Diabetes
Our team has a particular interest in evaluating the molecular mechanisms of metabolic surgery and how these can develop novel therapies and policies to address the epidemics of obesity, cardiovascular disease metabolic syndrome and cancer. Detailed topics include:

• Molecular mechanisms of Diabetes Resolution after Metabolic Surgery
• Systems Biology of Obesity and Bariatric Surgery
• Gut Microbial Effects of Surgery
• Cardiovascular & CardioRenal benefits of Metabolic procedures
• Anti-cancer effects of Bariatric Operations
• Metabolic Surgical Sleep Apnea Resolution
• Social Networking Services and Obesity-Metabolic Syndrome Management
• Regenerative medicine

Evidence Synthesis and Large Database Analysis
We are a leading academic department in the fields of:

• Comparative effectiveness
• Clinical trial evidence synthesis
• Complex clinical trial design
• Population screening
• Healthcare simulation
• Health economics and cost effectiveness
• Systematic reviews and standard meta-analysis
• Network meta-analysis and umbrella meta-analysis
• Hierarchical modeling and bayesian statistics
• Diagnostic accuracy
• Bibliometrics
• Quality of life analysis

Academic Performance and Social Network Analysis
Our group is conducting novel research in academic performance including performance metrics and benchmarking, Academic healthcare leadership and mentorship, Academic healthcare network analysis, and performance outcomes including balanced scorecards.

Economics, Global Health and Health Policy
We are utilising global health databases and financial models in guiding national and international policy on the economic determinants of improved health outcomes.

Surgical Innovation
Appraisal of novel technologies, robotic surgery, minimally invasive approaches, healthcare business models and quantification of health innovations.

Researchers

• Professor Thanos Athanasiou
• Mr Hutan Ashrafian

Collaborators

Dr Pietro Panzarasa, Ms Leanne Harling, Mr George Garas, Mr Omar Jarral, Ms Isabella Cingolani, Professor Xiao Yun Xu, Professor Sian E Harding, Mr Chris Rao and Mr Vanash Patel

Genomics, metabolomics and integrative biology in neuroendocrine tumours

Our aim is to identify novel biomarkers for Neuroendocrine Tumours (NET) which would allow personalised management during the patient journey. By concurrent collection of multiple “omics” data and a subsequent search for statistical associations, we will provide a personalised multi-analyte molecular disease signature. Our preliminary data underline the potential of “omics” in a personalised approach to management of NET patients.

Metabonomics: Partial least squares-discriminant analysis differentiated between NET and healthy samples with accuracy. Orthogonal partial least squares-discriminant analysis was able to distinguish between SB NET and PNET. Subclass analysis also demonstrated class separation between secreting and non-secreting NET and those with metastases.

miRNAs: Two independent miRNA profiling experiments were performed including primary SBNET, their metastases and normal tissues. We have evaluated potentially targeted genes by performing integrated computational analyses. We have discovered 39 miRNAs significantly deregulated in SBNET. Two miRNAs were significantly downregulated in LN and liver metastases. Furthermore, we identified upregulated gene targets which could contribute to disease progression.

Transcriptoma analysis: We have examined whether a blood-based multianalyte neuroendocrine gene transcript assay (NETest) would define tumor cytoreduction and therapeutic efficacy. A polymerase chain reaction-based analysis of 51 genes was performed. Disease activity was scaled 0-100%. Resection reduced NETest (P < .0001). NETest decreases correlated with diminished tumor volume. Cytoreduction significantly reduced NETest.

Other Trials:

1. Radiomics in NET (A high-throughput extraction of quantitative imaging parameters, extracted from conventional medical imaging, to improve NET patients prognostic information)
2. RADIOCYST –RADIONET trial in pancreatic tumours (Endoscopic radiofrequency ablation of pancreatic cystic tumours and neuroendocrine tumours of the pancreas)

Researchers

• Professor Andrea Frilling
• Professor Justin Stebbing
• Dr Leandro Castellano
• Mr James Kinross
• Ashley K. Clift
• Anna Malczewska

Bariatric surgical researchers at Imperial are performing a large number of clinical trials to determine optimal surgical and minimally invasive treatments for the treatment of obesity.

Remission of Type 2 Diabetes After Bariatric Surgery
Bariatric surgery is the only effective long-term treatment for obesity and can cause early weight-loss independent remission of type 2 diabetes in some patients, the mechanisms of which are unknown. Due to the risks and complications associated with bariatric surgery there is a need to predict which patients will achieve type 2 diabetes remission, and to better understand the mechanisms behind this phenomenon.

Doctoral researcher Olivia Szepietowski is working under her primary supervisor Professor Alex Blakemore, and co-supervisors Mr Sanjay Purkayastha and Professor Kevin Murphy on The Personalised Medicine for Morbid Obesity (PMMO) clinical trial, which aims to:

• Investigate some of the genetic factors underlying type 2 diabetes remission after bariatric surgery by studying changes in gene expression profiles in insulin-responsive tissues before and after surgery
• Identify clinical predictors of post-surgery diabetes remission
• Identify gene transcripts that are predictive of post-surgery diabetes remission

Breath profiling of metabolic changes following Bariatric surgery
Volatile organic compounds (VOCs) in breath can be quantified using mass spectrometry techniques and are the end products of several metabolic processes within the body. The aim of this clinical research is to quantify changes in breath VOCs observed in response to metabolic changes following bariatric surgery. Breath samples are taken from patients at several points along their clinical pathway and analysed using Gas Chromatography Mass Spectrometry and Selected Ion Flow-Tube Mass Spectrometry. The primary patient group being studied are obese patients with diabetes. Specific objectives of this research are to: 

• Determine changes in the metabolic breath profile of patients with diabetes undergoing bariatric gastric bypass
• Identify if a correlation exists between changes seen in the breath profile of patients following bariatric gastric bypass and the resolution of diabetes
• Examine if breath profiling can be used to non-invasively monitor diabetic control in bariatric surgical patients

Researchers

• Mr Sanjay Purkayastha
• Professor Alex Blakemore
• Mr Ahmed Ahmed
• Professor Elaine Holmes
• Mr Hutan Ashrafian
• Mr Nicholas Penney

The Imperial College Ophthalmic Research Group (ICORG) coordinates all ophthalmology research done within the Department of Cancer and Surgery and Western Eye Hospital, promoting multidisciplinary research and collaborations within and outside Imperial College. The ICORG is dedicated to establishing new methods of diagnosis of early disease to avoid disability, identifying early markers of cell processes in neurodegenerative disease and investigating new treatments for low vision and blindness, including developing novel modes of drug delivery and improved treatment strategies. 

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• Imperial College Ophthalmology Research Group

A quality improvement programme implementing the principles of ‘incremental gains’ to the whole peri-operative pathway. The research is focussed on assessing the impact of multi-modal personalised prehabilitation to post-operative outcomes and understanding the factors that predict adherence to prehabilitation. It Integrates patient engagement through using the principles of co-design to improve peri-operative care and will assess the role of peri-operative remote monitoring of patients (PROMPT) on adherence to prehabilitation and post-operative rehabilitation.

Researchers

• Mr Krishna Moorthy

Randomised controlled trials (RCTs) are perceived to provide the highest level of evidence from clinical studies. However, surgical RCTs are difficult to conduct and analyse especially with regards to the way operations are performed. Furthermore, performance of new surgical techniques can be affected by a surgeon’s phase on the learning curve. Hence, a robust Surgical Quality Assurance system is required in order to ensure that all surgeons participating in a clinical trial have reached a certain level of competency in performing the operations required.

Surgical Quality Assurance involves three components:

1. Standardisation of the technique(s)
2. Development of an operation manual and competency assessment tool (CAT)
3. Pre-trial assessment and trial monitoring using CAT and human reliability analysis

Our group, led by Professor George Hanna, provide the expertise in competency assessment methods, learning curve evaluation and human factors analysis.

Researchers

• Professor George Hanna

Prostate cancer needs the hormone testosterone to grow. One of the treatments for prostate cancer is hormone therapy which reduces the level of testosterone. To begin with, hormone therapy was mainly used for prostate cancer that had grown outside the prostate and couldn’t be removed with surgery. But it is now sometimes used for patients who have earlier stage prostate cancer.

Professor Paul Abel is conducting a trial comparing oestrogen patches that stick on the skin with hormone injections for prostate cancer, supported by Cancer Research UK called the PATCH trial.

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• PATCH trial 

Researchers

• Professor Paul Abel

Research interests include the molecular biology of vascular conditions (arterial and venous) and biomarker discovery; the efficacy of novel and existing treatments for abdominal aortic aneurysm, varicose veins and venous ulceration; the development and validation of patient reported outcome measures and improvements in service delivery.

Our scientific research is highly translational with a focus on metabonomics, surgical and non-surgical management of a range of venous conditions. We have a strong collaborative history with the Division of Computational and Systems Medicine and with other vascular and statistical units around the country.

With the support of the National Institute for Heath and Care Excellence (NICE) we are conducting population studies for chronic venous disease. Research is ongoing for the design and testing of medical devices for superficial and deep venous disease with industry support.

Research areas

• Abdominal aortic aneurysm 
• Varicose veins
• Venous ulceration
• Chronic venous disease
• Medical devices for superficial and deep venous disease
• Improving compliance with antihypertensive medication.

Current clinical trials and observational studies

• The British Society of Endovascular Therapy -ConformabLe EndoVascular Aneurysm Repair (BSET-CLEVAR) Registry: Prospective, multi-centre, observational cohort study designed to collect real-world clinical data on patients with abdominal aortic aneurysm (AAA) undergoing treatment by a novel endovascular device (GORE EXCLUDER Conformable AAA Endoprosthesis with ACTIVE CONTROL) at a number of specialist UK hospitals. 
• Early Venous Reflux Ablation Ulcer Trial (EVRA) A randomised clinical trial to compare early versus delayed endovenous treatment of superficial venous reflux in patients with chronic venous ulceration. 
• Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Examining the benefit of graduated compression stockings as an adjunct to low-dose low molecular weight heparin in the prevention of venous thromboembolism in elective surgical inpatients, identified as moderate or high risk for venous thromboembolism. 

Completed clinical trials

• Improve trial Emergency surgery randomised trial to assess whether a strategy of endovascular aneurysm repair versus open repair reduces early/mid-term mortality for patients with ruptured abdominal aortic aneurysms.

Researchers

• Mr Colin Bicknell
• Professor Alun Davies
• Professor Roger Greenhalgh
• Professor Janet Powell