Wales Cancer Research Conference - Programme and abstracts

Wales Cancer Research Conference 2024

Inspiring success: Building on our strengths

4 March 2024

National Museum Cardiff Programme and abstracts

We will be filming and taking photographs during the Wales Cancer Research Conference. All film/photos will be used for PR and marketing purposes promoting the Wales Cancer Research Centre and partners. If you would prefer not to be included in photographs, please let a member of our Hub team know before the end of the conference.

Byddwn ni’n ffilmio ac yn tynnu lluniau yn ystod Cynhadledd Ymchwil Canser Cymru.

Bydd yr holl ffilmiau/lluniau’n cael eu defnyddio at ddibenion cysylltiadau cyhoeddus a marchnata er mwyn hyrwyddo Canolfan Ymchwil Canser Cymru a phartneriaid. Os byddai’n well gennych chi beidio â chael eich cynnwys yn y lluniau, rhowch wybod i aelod o’n tîm cyn diwedd y gynhadledd.

Dear delegates,

Professor Mererid Evans Director, Wales Cancer Research Centre

I am delighted to welcome you to the Wales Cancer Research Conference 2024!

At the Wales Cancer Research Centre (WCRC) we work in partnership to develop and support excellent cancer research across Wales. Aligned with the all-Wales Cancer Research Strategy (CReSt), we're focused on growing the cancer research base in Wales for the benefit of our population and patients.

Today will bring together clinical and non-clinical cancer researchers and stakeholders from across Wales and the UK, to highlight our recent successes and plans for the future. Prepare for a day that not only celebrates research and innovation, but also serves as a golden opportunity for networking and fostering valuable collaborations.

The superb abstracts presented in this brochure and the posters on display at the conference showcase the breadth of ground-breaking cancer research taking place across Wales The posters will be judged in three categories which are integral to WCRC’s ethos: patient and public involvement, scientific excellence, and impact in practice. These three categories span the six CReSt priority research themes, and underpin the value of Welsh scientific contribution to cancer research as a whole.

Today would not be possible without the generosity of our sponsors, to whom we’re very grateful.

Let the Wales Cancer Research Conference 2024 commence!

Yr Athro Mererid Evans

Cyfarwyddwr, Canolfan Ymchwil Canser Cymru

Annwyl Gynrychiolwyr,

Mae’n bleser gennyf eich croesawu i Gynhadledd Ymchwil Canser Cymru 2024!

Yng Nghanolfan Ymchwil Canser Cymru (WCRC) rydym yn gweithio mewn partneriaeth i ddatblygu a chefnogi ymchwil canser rhagorol ledled Cymru. Yn unol â Strategaeth Ymchwil Canser Cymru Gyfan (CReSt), rydym yn canolbwyntio ar dyfu’r sylfaen ymchwil canser yng Nghymru er budd ein poblogaeth a’n cleifion.

Bydd heddiw yn dod ag ymchwilwyr canser clinigol ac anghlinigol a rhanddeiliaid o bob rhan o Gymru a’r DU ynghyd, i dynnu sylw at ein llwyddiannau diweddar a’n cynlluniau ar gyfer y dyfodol Paratowch ar gyfer diwrnod sydd nid yn unig yn dathlu ymchwil ac arloesi, ond sydd hefyd yn gyfle euraidd i rwydweithio a meithrin cydweithrediadau gwerthfawr

Mae’r crynodebau gwych a gyflwynir yn y llyfryn hwn a’r posteri sy’n cael eu harddangos yn y gynhadledd yn arddangos ehangder yr ymchwil canser arloesol sy’n digwydd ledled Cymru. Bydd y posteri'n cael eu beirniadu mewn tri chategori sy'n rhan annatod o ethos WCRC: cyfranogiad claf a'r cyhoedd, rhagoriaeth wyddonol, ac effaith ymarferol. Mae'r tri chategori hyn yn rhychwantu chwe thema ymchwil blaenoriaethol CReSt, ac yn tanategu gwerth cyfraniad gwyddonol Cymru at ymchwil canser yn ei gyfanrwydd.

Ni fyddai heddiw yn bosibl heb haelioni ein noddwyr. Rydym yn ddiolchgar iawn iddynt. Gadewch i Gynhadledd Ymchwil Canser Cymru 2024 ddechrau!

Inspiring success: Building on our strengths

This year’s theme focuses on showcasing impactful research from Wales, with highlights from across the UK to provide broader insights. This will help us to deliver collectively on CReSt, Wales’ first national cancer research strategy.

Today’s programme has been structured around the six CReSt priority themes:

Precision and mechanistic oncology

Looking at how genetics can affect who gets cancer, how that cancer behaves, and finding ways to treat cancers with particular genetic 'signatures'.

Cancer clinical trials

Bringing promising new treatments to patients in trials and testing new ways of giving existing treatments.

Immuno-oncology

Understanding how our bodies' immune responses change when cancer develops, and finding ways to use the immune system to help fight cancer.

Palliative and supportive oncology

Finding the best ways to look after patients with cancer, such as pain control, side effect management and mental health support.

Radiotherapy

Exploring how radiotherapy can kill cancer cells while limiting the impact on the rest of the body.

Prevention, early detection, primary care and health services research

Finding new ways to prevent cancer and detect it early, and making sure that health services in Wales are underpinned by strong science.

The CReSt themes are areas where Wales shines already, and by working together and focusing our efforts we can achieve even more. This maximises research opportunities for patients and ensures we keep learning and applying new advances within and beyond the clinic. Everyone involved in cancer research in Wales has a part to play in making the CReSt strategy become a reality, and we hope this day will inform, inspire and motivate you along your journey.

Llwyddiant sy’n ysbrydoli:

Adeiladu ar ein cryfderau

Ffocws y thema eleni bydd tynnu sylw at ymchwil effeithiol o Gymru, gydag uchafbwyntiau hefyd o ledled y DU er mwyn rhoi darlun ehangach. Bydd hyn o gymorth i ni allu cyflawni ar y cyd dros CReSt, sef strategaeth ymchwil cansergenedlaethol gyntaf Cymru.

Strwythurir rhaglen heddiw o amgylch chwe o themâu blaenoriaeth CReSt:

Oncoleg fecanistig a manwl-gywir

Edrych ar sut y gall geneteg effeithio ar bwy sy'n cael canser, sut mae'r canser hwnnw'n ymddwyn, a chanfod ffyrdd o drin canserau â 'llofnodion' genetig penodol.

Treialon clinigol ym maes canser

Dod â thriniaethau newydd addawol i gleifion mewn treialon a phrofi ffyrdd newydd o gynnig triniaethau presennol.

Imiwno-oncoleg

Deall sut mae ymatebion imiwn ein cyrff yn newid pan fydd canser yn datblygu, a dod o hyd i ffyrdd o ddefnyddio'r system imiwnedd i helpu i frwydro yn erbyn canser.

Oncoleg gefnogol a lliniarol

Dod o hyd i'r ffyrdd gorau o ofalu am gleifion â chanser, fel rheoli poen, rheoli sgîl-effeithiau a chymorth iechyd meddwl.

Radiotherapi

Ystyried sut y gall radiotherapi ladd celloedd canser tra'n cyfyngu ar yr effaith ar weddill y corff.

Ymchwil yn ymwneud ag atal, canfod cynnar, gofal sylfaenol a gwasanaethau iechyd

Dod o hyd i ffyrdd newydd o atal canser a’i ganfod yn gynnar, a gwneud yn siŵr bod gwasanaethau iechyd yng Nghymru yn cael eu hategu gan wyddoniaeth gref.

Mae themâu CReSt yn feysydd lle mae Cymru'n rhagori ynddynt eisoes, a thrwy gydweithio a chanolbwyntio ein hymdrechion, gallwn gyflawni mwy hyd yn oed. Bydd hyn yn caniatáu i gleifion fanteisio i’r eithaf ar gyfleoedd ymchwil a sicrhau ein bod yn parhau i ddysgu o’r datblygiadau newydd a welir o fewn a thu hwnt i'r clinig, a’u cymhwyso. Mae gan bawb sydd ynghlwm ag ymchwil canser yng Nghymru ran i'w chwarae wrth wireddu'r strategaeth CReSt ac rydym yn gobeithio y bydd y diwrnod hwn yn ddefnyddiol, yn eich ysbrydoli ac yn eich ysgogi hyd eich taith.

About the Wales Cancer Research Centre

The Wales Cancer Research Centre is based at Cardiff University and funded by Health and Care Research Wales and our funding partners at Cardiff University, Swansea University, Bangor University, Velindre NHS Trust and Cardiff and Vale University Health Board. We work collaboratively to support cancer research across Wales and to drive progress in line with Wales’ cancer research strategy, CReSt

As part of WCRC’s role in CReSt implementation, we have opportunities for you to get involved:

* Join one of our newly launching multi-disciplinary research groups *

*Join our bioinformatics network*

*Tap into the skills of our PPI network*

*Use our signposting resources, such as our early career researcher guide *

Sign up to our monthly newsletter to stay up to date with news, events, funding opportunities and more from the Wales Cancer Research Centre

Gwybodaeth am Ganolfan Ymchwil Canser Cymru

Wedi’i lleoli ym Mhrifysgol Caerdydd, mae’r Ganolfan Ymchwil Canser Cymru wedi'i hariannu gan Ymchwil Iechyd a Gofal Cymru, yn ogystal â'n partneriaid ariannol ym Mhrifysgol Caerdydd, Prifysgol Abertawe, Prifysgol Bangor, Ymddiriedolaeth GIG Felindre, a Bwrdd Iechyd Prifysgol Caerdydd a'r Fro. Rydym yn gweithio ar y cyd i gefnogi ymchwil canser ledled Cymru ac i yrru cynnydd yn ei flaen yn unol â strategaeth ymchwil canser Cymru, sef CReSt. Mynnwch y wybodaeth ddiweddaraf drwy ein cylchlythyr i gael gwybod am ein mentrau a'n digwyddiadau newydd, wrth i ni eu cyhoeddi drwy gydol y flwyddyn

Yn rhan o rôl y Ganolfan Ymchwil Canser Cymru wrth weithredu CReSt, mae sawl cyfle i chi gymryd rhan:

* Ymunwch ag un o'r grwpiau ymchwil amlddisgyblaethol a lansiwyd yn ddiweddar*

*Ymunwch â'n rhwydwaith biowybodeg*

*Manteisiwch ar sgiliau rhwydwaith Cynnwys y Cleifion a’r Cyhoedd (PPI) *

* Defnyddiwch ein hadnoddau, fel ein Canllawiau i Ymchwilwyr ar ddechrau eu gyrfa *

Meet today’s sponsors

Part of the NHS Executive for Wales, the National Strategic Clinical Network for Cancer is guided and overseen by the Wales Cancer Network Board. Detecting cancer earlier and person centred care are at the heart of everything we do. Our programmes are driven by clinical knowledge, patient experience, research and embracing new technologies and developments in cancer care.

The Advanced Therapies Wales (ATW) programme is responsible for delivering the Welsh Government’s ambition for developing the Advanced Therapies landscape in Wales. Advanced Therapies refers to innovative new treatments involving cell and gene therapies with the potential to improve disease outcomes across a range of disease sites, including cancer. ATW works with key stakeholder organisations including NHW Wales, to support NHS readiness to deliver advanced therapies both in the standard care setting and research sector.

A global pharmaceutical company with a major UK presence. Our purpose is to push the boundaries of science to deliver life-changing medicines The best way we can help patients is to be science-led and share this passion with the scientific, healthcare and business communities of the UK.

Cancer Research Wales is the nation’s only independent cancer research charity where all money raised is spent in Wales Founded in 1966 the organisation has a rich history of funding cancer research in universities, hospitals, primary care, and communities across Wales. A diverse range of areas are funded, several of national strategic importance. Cancer Research Wales supports major project grants, clinical trials, academic and clinical PhD studentships and innovation grants across the cancer research landscape These include fundamental and translational cancer research, early diagnosis, better treatments, and health systems and cancer outcomes research.

Cytiva and Pall Life Sciences have come together to deliver the breadth, depth, and scale researchers and biopharma need to advance future therapeutics from discovery to delivery. Together, as Cytiva, we supply the tools and support our customers need to work better, faster, and safer, leading to the delivery of transformative medicines to patients. Our combined portfolio includes well-recognized names such as Allegro™, Supor™, iCELLis™, and Kleenpak™, in addition to ÄKTA™, Amersham™, Biacore™, FlexFactory™, HyClone™, MabSelect™, Sefia™, Whatman™, and Xcellerex™ Visit cytiva.com to learn more.

At Roche UK, we focus our energy and investment in developing tests and treatments that change lives and give us more quality time with the people we love. And, together with others, we’re solving healthcare’s greatest challenges; helping to achieve better results by connecting early diagnosis to targeted treatments and ongoing support.

Tenovus Cancer Care is a Wales-based charity giving help, hope, and a voice to everyone affected by cancer. Its wide range of services offers information, advice, and specialist support. Its campaigning and policy work is informed by Wales-specific cancer data and the real experiences of people affected by cancer to drive the changes that make a difference, focused in areas it can have the most impact. Its current focus is on raising awareness and improving outcomes for the less survivable cancers Its community of supporters, volunteers, and fundraisers help raise the vital funds to make this possible.

Conference speakers

9:30 - 11:30 Conference chair

Prof Mererid Evans is the director for the Wales Cancer Research Centre, as well as a consultant clinical oncologist at Velindre Cancer Centre in Cardiff, specialising in head and neck cancer A graduate of the University of Wales College of Medicine, she received a PhD in 2001 for her research into immune responses to Human Papillomavirus (HPV) in patients with cervical cancer. Prof Evans is now chief investigator of three multi-centre clinical trials (PATHOS, Best-Of and PEARL) which all seek to develop kinder treatments for patients with head & neck cancer.

Keynote speakers

Prof Eva Morris is a Professor of Health Data Epidemiology within the Oxford Big Data Institute and the Nuffield Department of Population Health, where she leads a group focused on the use of routinely collected health data for patient benefit. Prof Morris leads the UK Colorectal Cancer Intelligence Hub, which is responsible for establishing a UK wide colorectal cancer data repository (CORECT-R)

Dr Andrew Furness is Consultant Medical Oncologist based at the Royal Marsden Hospital. He treats patients with cancers of the skin and kidney and leads clinical research in solid tumour cellular therapy in a pan tumour manner He is a Team Leader and Clinical Lead of the Centre for Translational Immunotherapy at the Institute of Cancer Research, where his research interests lie in translational immunology and cell-based immunotherapy. He leads the Solid Tumour Cellular Therapy subgroup of the British Society of Bone Marrow Transplantation and Cellular Therapy, and acts as faculty member of the European Society for Medical Oncology Tumour Immunology and Immunotherapy and Investigational Immunotherapy groups He is motivated to expand the reach of immunotherapy to a greater fraction of patients with solid tumours and hopes to achieve this through cell-based approaches and a better understanding of the biology underlying response and resistance to existingapproaches.

Professor Eva Morris

Professor Mererid Evans

Dr Andrew Furness

11:30

Patient and public involvement

Julie Hepburn had successful treatment for a stage 3 bowel cancer nine years ago and since that time has been heavily involved in public involvement, mainly in the cancer area She is currently the Lead Lay Research Partner for both the Wales Cancer Research Centre and the Experimental Cancer Medicine Centre at Cardiff and is involved in cancer research projects ranging from screening and early detection through to surgery, treatment and palliative care.

Lowri Griffiths is the Director of Support, Policy and Insight at Tenovus Cancer Care, with extensive experience at multiple leading cancer charities such as Macmillan and Bowel Cancer UK and also end of life charity, Marie Curie. She is the current Chair of the Wales Cancer Alliance, a coalition of charities working to prevent, improve care, fund research and influence policy in Wales

Lowri Griffiths

Mrs Julie Hepburn

Dr Helen Pearson

11:30 - 12:40

Precision and mechanistic oncology

Prof Kathreena Kurian is a professor of neuropathology and honorary consultant at Southmead Hospital, and she runs the Brain Tumour Research Centre based at Bristol Medical School, University of Bristol. Prof Kurian is the current Chair of the British Neuropathological Society Clinical Practice Committee, as well as sitting on the Tessa Jowell Brain Cancer Mission, and has previously been a member of the National Cancer Research Institute Brain Tumour Group.

Dr Helen Pearson is a senior lecturer in prostate cancer at The European Cancer Stem Cell Research Institute (Cardiff University, School of Biosciences). Dr Pearson is a Cancer Research UK Career Development Fellow and her research group focuses on delineating the molecular mechanisms that underpin prostate cancer growth and therapeutic resistance, with a view to improving patient care through the identification of novel predictive biomarkers and therapeutic strategies. Dr Pearson is also an Associate Director of the Wales Cancer Research Centre.

Prof Duncan Bairdis a professor of cancer and genetics at Cardiff University, as well as the leadfor Genetic and Genomic Medicine and co-lead of theCReSt Precision and Mechanistic Oncology theme. His research group focuses on telomere biology, ranging from mechanistic discovery science to translational and applied work. Technology developed by the laboratory is used for clinical diagnostics at NHS centres across the UK and abroad Prof Baird’s work has been extensively published injournals such as Nature Genetics, Genome Research and Nature Communications.Prof Baird’s lab has attracted substantial funding from Cancer Research UK, the USNational Institutes of Health, Blood Cancer UK, Cancer Research Wales and Health and CareResearch Wales.

Dr Magda Meissner is a Medical Oncology Consultant at Velindre Cancer Centre, holding the position of Clinical Senior Lecturer at Cardiff University. Additionally, she serves as the Clinical Liquid Biopsy Lead at All Wales Medical Genetics Laboratory (AWMGS). Dr Meissner is committed to advancing translational clinical trials, and was awarded a clinical research fellowship by the Welsh Cancer Research Centre, based at the early phase clinical trials unit in Velindre Cancer Centre. Currently, she leads the QuicDNA study, a pioneering project investigating the use of non-invasive liquid biopsy for lung cancer diagnosis. This study is supported by substantial grants from Health and Care Research Wales, Moondance Cancer Initiative, Craig Maxwell fund, and multiple commercial grants. Dr Meissner also holds the role of Precision and Mechanistic Oncology CReSt Theme co-Lead

Professor Kathreena Kurian

Professor Duncan Baird (Session Chair)

Dr Magda Meissner (Session Chair)

11:30 - 12:40

Palliative and supportive oncology

Prof Simon Noble is an honorary consultant in Palliative Medicine at Aneurin Bevan University Health Board, Director of the Division of Population Medicine as well as codirector of the Marie Curie Palliative Care Research Group, based at Cardiff University His main research focus is cancer-associated thrombosis, with an emphasis on management of thrombosis in advanced cancer. Prof Noble is passionate about advocating for patient-partner working in all aspects of his practice. Prof Noble has delivered lectures in over 40 countries and published articles in the British Medical Journal, Lancet and Nature Reviews. Prof Noble is also a palliative and supportive oncology CReSt Theme co-Lead.

Richard Simcock first joined Macmillan Cancer Support as a National Clinical Advisor in 2014 and was appointed Chief Medical Officer in 2022. In his role, Richard co-leads the organisation’s Centre of Clinical Expertise, which is responsible for connecting with healthcare professionals delivering cancer care and gathering clinical insight to support the charity’s work. Alongside this, Richard is a Consultant Clinical Oncologist at University Hospitals Sussex NHS Foundation Trust, where he provides clinical care to people with breast cancer. Having initially trained in palliative medicine, Richard switched to oncology and completed five years of post-graduate cancer specialist training in London and the South East, followed by a fellowship at the Sydney Cancer Centre in Australia. Richard is also an Honorary Professor at Brighton and Sussex Medical Schools, a regular contributor to journals and textbooks, a Co-Editor of the ‘ABC of Cancer Care’ and an Associate Editor at BMJ Oncology. Richard is particularly interested in innovation in cancer care, patient communication and shared decisionmaking, personalised medicine and multidisciplinary working.

Dr Idris Baker is a Consultant in Palliative Medicine at Tŷ Olwen in Swansea, working mainly in community palliative care. He is a former clinical director of the South West Wales Cancer Centre and holds honorary appointments at the universities of Swansea, Cardiff and Amsterdam. He is National Clinical Lead for Palliative & End of Life Care in Wales, working as part of the National Clinical Programme. This new Programme aims to make good use of data and evidence to support equitable palliative care for people of all ages and across statutory & voluntary sectors.

Professor Simon Noble

Professor Richard Simcock

Dr Idris Baker (Session Chair)

Radiotherapy

Dr Anna Wilkins is a Clinician Scientist at the Institute of Cancer Research in London, and an Honorary Consultant in Clinical Oncology at the Royal Marsden Hospital. She has a particular interest in the biology of cancer-associated fibroblasts and how these, and other non-cancerous cells, impact radiotherapy outcomes in bladder and prostate cancer. Anna was previously awarded a Crick Postdoctoral Clinical Fellowship, in the Sahai lab and used this opportunity to pursue research into the impact of radiotherapy on the tumour microenvironment. Since completion of her fellowship, Dr Wilkins has continued at The Francis Crick Institute as a Visiting Scientist whilst leading the Stromal Radiobiology Group at the ICR.

Dr Sarah Gwynne has been a consultant clinical oncologist in the South West Wales Cancer Centre since 2012. She has been an honorary associate professor at Swansea University since 2020. Her research interests are in improving outcomes in oesophagus and stomach cancer and she has been part of a series of UK radiotherapy trials in this area, with particular focus on the quality assurance (QA) of the radiotherapy within those trials More than a decade of QA (undertaking her MD in Cardiff University in 2012 on the radiotherapy QA of the SCOPE trial in definitive chemoradiotherapy in oesophageal cancer) culminated in her appointment as the medical lead for the National Institute for Health and Care Research Radiotherapy Trials Quality Assurance group in July 2023. She is currently working towards a clinical trial looking at the role of radiotherapy for inoperable stomach cancer.

Dr James Powell is a neuro-oncology consultant at Velindre Cancer Centre, and specialises in treatment of primary and secondary brain tumours and sees patients from across Wales. Dr Powell’s clinical research includes being the local PI for a number of clinical trials in brain tumours, including the PARADIGM trials which are investigating the efficacy of olaparib for the treatment of aggressive brain tumours, and is a collaborator on the first UK national proton radiotherapy brain tumour trial. He has led collaborative brain tumour research studies with the Cardiff University Brain Research Imaging Centre (CUBRIC) which have involved patients from across South Wales. He is also the CReSt theme lead for Radiotherapy.

Dr Sarah Gwynne

Dr Anna Wilkins

Dr James Powell (Session Chair)

Cancer clinical trials

Dr Sadie Jones is an academic consultant gynaecology oncology surgeon in the University Hospital of Wales. Dr Jones has previously chaired the Wales Gynaecology Oncology Multi-Disciplinary Research Group, and is now the early/mid-career representative for the Wales Cancer Research Centre. Her academic interests are around ovarian cancer care for which she leads several research studies including the PICCOS trial – the subject of her talk today.

Dr Magda Meissner is a Medical Oncology Consultant at Velindre Cancer Centre, holding the position of Clinical Senior Lecturer at Cardiff University. Additionally, she serves as the Clinical Liquid Biopsy Lead at All Wales Medical Genetics Laboratory (AWMGS). Dr Meissner is committed to advancing translational clinical trials, and was awarded a clinical research fellowship by the Welsh Cancer Research Centre, based at the early phase clinical trials unit in Velindre Cancer Centre. Currently, she leads the QuicDNA study, a pioneering project investigating the use of non-invasive liquid biopsy for lung cancer diagnosis. This study is supported by substantial grants from Health and Care Research Wales, Moondance Cancer Initiative, Craig Maxwell fund, and multiple commercial grants Dr Meissner also holds the role of Precision and Mechanistic Oncology CReSt Theme co-Lead.

Dr Magda Meissner

Dr Sadie Jones

Cancer clinical trials

Prof Richard Adams is a professor and honorary consultant clinical oncologist at Cardiff University and Velindre Cancer Centre. Furthermore, Prof Adams is the codirector of the Centre for Trials Research, a large academic clinical trials unit, as well as the clinical director of the Wales Cancer Biobank in Cardiff University. His research focuses on development and delivery of cancer clinical trials, with a spotlight on collaborative team work to achieve better patient outcomes. His research has been published in journals including Lancet Oncology, JNCI and JCO.Prof Adams is medical advisor for Bowel Cancer UK and sits on numerous national funding committees for clinical research. Internationally he is on the executive committee for ARCAD and UK representative on the International Rare Cancer Initiative (IRCI) anal cancer group and the European Networkfor Gastrointestinal Cancer Collaboration (ENGIC). Prof Adams is also a cancer clinical trials CReSt Theme co-Lead.

Professor Steven Knapper

Prof Steven Knapper is professor within the Division of Cancer and Genetics at Cardiff University, as well as an Honorary Consultant Haematologist at the University Hospital of Wales. Prof Knapper’s academic and research focus is haematological cancers, particularly acute myeloid leukaemia and myeloproliferative neoplasm Prof Knapper is deputy chair of the UK AML Working Group and co-leads the AML18 trial, an acute myeloid leukaemia study active across ~90 centres internationally. He is also the lead for Cardiff University School of Medicine medical undergraduate haematology teaching. Prof Knapper is chair of the CRUK Experimental Cancer Medicine Centres Haematology Group, Deputy Medical Director of the UK Trials Acceleration Programme and cancer clinical trials CReSt Theme co-Lead.

Professor Richard Adams (Session Chair)

(Session Chair)

Dr Sheeba Irshad

Immuno-oncology

Dr Sheeba Irshad is Clinical Reader and a breast cancer medical oncologist at King’s College London and Guy’s and St Thomas’ NHS Foundation Trust. Following her return from The Sidney Kimmel Comprehensive Cancer Center at John’s Hopkins University, she was appointed as a clinical deputy head of King’s College London’s Breast Cancer Now Research Unit Programme in 2018. As a Cancer Research UK-funded clinician scientist, she has established an independent research group focused on understanding the immune landscape of chemotherapy-resistant breast cancers. She is the chief investigator of the multi-centre SOAP study: Sars-Cov-2 for Cancer Patients, and the Outlier study investigating the immune surveillance mechanisms in ‘exceptional responders’ of stage 4 cancers.

Professor Andrew Sewell

Prof Andrew Sewell is a professor based in the Division of Infection and Immunity at Cardiff University. He is a Wellcome Trust Senior Investigator and has been funded by Wellcome for over 25 years. During this time he has investigated the role of T-cells during infection, transplant rejection and autoimmune disease More recently, his interest has pivoted towards how T-cells clear cancer and how they might be engineered for T-cell therapy. His group are part of the $25M Cancer Grand Challenge that aims to build T-cell therapies for solid childhood cancers.

Immuno-oncology

Prof Awen Gallimore is a professor within the Division of Infection Immunity and CoDirector of Systems Immunity Research Institute at Cardiff University, and immunooncology CReSt Theme co-Lead. Prof Gallimore’s research career began in Oxford, where she established a lab (with Wellcome Trust funding) to explore the regulation of anti-viral and anti-cancer immunity. Prof Gallimore is now based at Cardiff University where her lab is funded by Cancer Research UK, Cancer Research Wales, The Wellcome Trust and Breast Cancer Now. Her research focuses on anti-cancer immunity, spanning basic discovery science through to testing novel immunotherapies in patients. Prof Gallimore is Chair of the Immunology Expert Review Panel at Cancer Research UK and treasurer of the British Society for Immunology Tumour Affinity Group.

Prof Alan Parker is a professor of translational virotherapies, and head of Section of Solid Cancers within the Division of Cancer and Genetics at Cardiff University. Alan is also immuno-oncology CReSt Theme co-Lead. Alan leads a laboratory group where the research is focused on developing virotherapies for treatment of cancer, funded by Stand up to Cancer, Cancer Research UK, Cancer Research Wales and the Pancreatic Cancer Research Fund. Alan is Founder and CSO of Trocept Therapeutics (part of Accession Therapeutics Ltd) who are taking a Cardiff developed virotherapy to first in human clinical evaluation. Alan is treasurer and board member of the British Society for Gene and Cell Therapy, as well as a STEMNet ambassador, passionate about conveying science to, and engaging with, the lay community.

Professor Awen Gallimore (Session Chair)

Professor Alan Parker (Session Chair)

Dr Lee Parry

Professor Paul Dyson

Dr Samuel Merriel

Population health-based cancer prevention and early detection

Dr Lee Parry leads the Prevention and Early Detection of Cancer group at Cardiff University’s School of Biosciences. His research is focused on the microbiome of intestinal and colorectal cancers. Dr Parry is a reviewer for 11 scientific journals including Trends in Endocrinology and BMC Cancer. He also sits on the grant reviewing committee for seven organisations including the American Institute of Cancer Research and the Medical Research Council.

Prof Paul Dyson is a molecular microbiologist based at Swansea University, whose research focuses on exploiting useful bacteria, particularly for early detection and therapeutic delivery in colon cancer. In 2018, his work was recognised as one of the UK's 100 best breakthroughs for its significant impact on people's everyday lives.

Dr Samuel Merriel is a GP in North-West England and NIHR Academic Clinical Lecturer within the Centre for Primary Care & Health Services Research at the University of Manchester. He leads a portfolio of studies focused on the early detection and prevention of cancer in primary care, and is Associate Editor and Editorial Board member for the British Journal of General Practice. Dr Merriel is also a Senior Editorial Board Member for BMC Cancer and has served on expert reference groups for NHS England, the National Institute for Health and Care Excellence (NICE), the National Cancer Research Institute, Movember, and Prostate Cancer UK.

Prof Sunil Dolwani is Professor of Gastroenterology and Honorary consultant gastroenterologist in Cardiff. He has a special interest in cancer data research and in new technology and integration into screening, prevention and early detection clinical trials of cancer. Prof Dolwani is also the Chief Medical Officer for the Cancer Data Driven Detection (CD3) program led by Cancer Research UK. Prof Dolwani is Cancer Theme lead for the Division of Population Medicine at Cardiff University anda population health-based cancer prevention and early detection CReSt Theme co-Lead, and Associate Director of the Wales Cancer Research Centre.

Professor Sunil Dolwani (Session Chair)

Panel speakers

Prof Katherine Brain is a professor within the Division of Population Medicine and Associate Director of the College of Biomedical and Life Sciences Population Health Research Theme at Cardiff University. Prof Brain’s research is focused on understanding the determinants of cancer symptom help-seeking behaviour and participation in cancer screening. She belongs to many international panels, including the US/UK Multi-Cancer Early Detection Consortium Health Equity workgroup and the European Code Against Cancer Working Group on Communication and Health Literacy. Prof Brain also acts as an advisor to NHS England on the Targeted Lung Health Check programme Prof Brain leads trials including TIC-TOC, a public awareness campaign designed to help people living in deprived communities recognise vague cancer symptoms. Prof Brain is also a population health-based cancer prevention and early diagnosis CReSt Theme Lead.

Dr Grace McCutchan

Dr Grace McCutchan is a Lecturer based in the School of Medicine, Cardiff University Her behavioural science research focuses on inequalities in cancer screening, prevention and early diagnosis. She has developed and tested various behavioural interventions to encourage earlier detection and prevention of cancer, including the Cancer Research Wales-funded study TIC-TOC, a non-specific cancer awareness campaign to support equitable access to Rapid Diagnostic Clinics.

Dr Heather Wilkes has been a GP in Briton Ferry, South Wales for over 28 years As a generalist she has been involved in developing many clinical and service provision areas. For the last 10 years she has been involved in developing cancer services, with roles including clinical & project lead for the first Rapid Diagnosis Centre (RDC) in 2017, based at Neath Port Talbot Hospital, Swansea Bay University Health Board (SBUHB) and was the Wales Cancer Network RDC National Programme Clinical Lead, 2021 – 23, leading on the roll out of RDCs and Vague/Non Specific Symptom Pathways across Wales. She is also Clinical Lead on the SBUHB/Moondance Cancer Initiative project (2021 – 24) piloting cancer site-specific RDC clinics, and is a member of the Cancer Research Wales Scientific Committee, and Moondance Cancer Initiative Clinical Advisory Group.

Professor Katherine Brain (Session Chair)

Dr Heather Wilkes

Panel speakers

Dr Lee Campbell, Head of Research, joined Cancer Research Wales in 2010 to provide oversight and research governance for the rich portfolio of charity-funded clinical and academic cancer research projects in Universities and Hospitals across Wales. During this time Lee has overseen the funding and development of a number of major cancer research projects of national strategic priority for Wales in the fields of primary care, early diagnosis and better treatments. As well as contributing to various aspects of cancer policy for Cancer Research Wales through Cross Party Groups and the Wales Cancer Alliance. Prior to joining Cancer Research Wales, Lee worked in a number of different academic research fields related to pharmaceutical science, drug delivery, pharmacology and cancer, and has published a number of research papers, abstracts and book chapters in these areas.

Ms Lisa Howells

Dr Sara Thomas

Lisa Howells has worked as a fund raiser for Cancer Research UK for 40 years and was delighted to be appointed as one of the Cwm Taf Cancer Champions for the Targeted Intensive Community-based campaign To Optimise Cancer awareness (Tic-Toc Study). Lisa has been employed by the National Federation of Women’s Institutes (Wales) for over 36 years and is currently the Events Officer for Wales.

Dr Sara Thomas is a consultant in Public Health with Cwm Taf Morgannwg (CTM) University Health Board, where Sara leads a number of programme areas including inequalities in cancer outcomes, Making Every Contact Count (MECC), Social Prescribing and Primary Care contribution to Population Health and Wellbeing. Sara established and chairs a multiagency ‘Reducing Cancer Inequalities and Raising Public Awareness Group’ in CTM. The group brings together health, education, third sector and academic partners to design and deliver interventions and projects to encourage earlier presentation, reduce inequalities and improve cancer outcomes Most recently Sara has been involved in developing a partnership between health and education to raise community and public awareness of cancer symptoms and screening via teaching modules for school children as part of the National Curriculum for Wales.

Dr Lee Campbell

Abstracts

CReSt Theme 1: Precision and mechanistic oncology

24/T11

Cardiff University

Emma A Swift

24/T12

Swansea University

Dr Claire Donnelly

24/T13

Cardiff University

Heba Elhaddad

Novel agents for positron emission tomography (PET) imaging and targeted drug delivery to αvβ6positive tumours

Clinical Application of Antibody Drug Conjugates and Exosomes as Advanced Therapeutics for Ovarian Cancer

Machine Learning and response to induction chemotherapy in patients with Acute Myeloid Leukemia 24/T14

Cardiff University

24/T15

Cardiff University

Kez Cleal

Kevin Norris

24/T16

European Cancer Stem Cell Research Institute, Cardiff University

Beatriz SalvadorBarbero

Enhancing Structural Variant Detection and Visualization in Cancer Genomics: Integrated Approaches with Dysgu and GW

High-resolution telomere analysis for clinical diagnostics

Key cell survival mechanisms allow KrasG12D cells to be retained in the competitive tissue environment of the adult pancreas

24/T17

Preclinical evaluation of a novel antibody drug conjugate for prostate cancer 24/T18 Cardiff University

Cardiff University

Daniel Turnham

Rehab Alanazi

Mechanisms underlying the required expression of S100A4 for proliferation and survival of AML blasts

Abstracts

CReSt Theme 2: Immuno-oncology

24/T21

Division of Infection and Immunity, Cardiff University

Mathew Clement

24/T22

Cardiff University

Stephanie Burnell

24/T23

Cardiff University

Rebecca Wallace

Manipulating T-cell immune responses in order to improve anti-Glioblastoma immunity

Developing a 3D colorectal organoid/T cell coculture model to test cancer immunotherapeutics

Generating hexon chimeric adenoviruses designed to circumvent neutralising anti-vector immunity

24/T24

Cardiff University

Rebecca Bayliss

“Precision Immunovirotherapies” expressing bispecific immune cell activators induce immune cell activation and tumour cell killing.

24/T25

Cardiff University

Hayley Timmins

ABC-12: Exploring the microbiome in patients (pts) with advanced biliary tract cancer (BTC) in a firstline study of durvalumab in combination with cisplatin/gemcitabine (cis/gem)

24/T26

Cardiff University

Kate Milward

Assessment of a pre-clinical viral-vectored cancer immunotherapy designed to harness anti-viral immunity against cancer cells

24/T27

Cardiff University

Luned Marged Badder

Delivery of suicide therapies using a precision virotherapy; novel approaches for pancreatic cancer

Abstracts

CReSt Theme 3: Radiotherapy

24/T31 South West Wales Cancer Centre Ryan Lewis Development of a Radiotherapy Dashboard

24/T32 South West Wales Cancer Centre Dr Amy Case

24/T33 Swansea University Shannon Rowlands

24/T34 Cardiff University

24/T35

Centre for Trials Research, Cardiff University

Jessica Oliver

Developing the role of radiotherapy for inoperable gastric cancer

Identifying and addressing barriers to clinical oncology trainees’ involvement in radiotherapy research in Wales

Radiotherapy Systemically Alters the Immunological Landscape in Patients with Oligometastatic Cancer

Ann White

A Randomised Open Label Multicentre Phase III Clinical Trial Evaluating Adjuvant Radiotherapy in Patients with High-risk Primary Cutaneous Squamous Cell Carcinoma AFTER Surgery: SCCAFTER Study Protocol

Code

CReSt Theme 4: Cancer Clinical Trials

Institution of submitting author

First author

24/T41

Medicines Discovery Institute, Cardiff University

24/T42 Cardiff University

Loren Waters

Dr Daniella Holland-Hart

24/T43

Centre for Trials Research, Cardiff University

24/T44 Cardiff University

24/T45 Velindre Cancer Centre

Margherita Carucci

Dr Kieran Foley

Abstract title

Proteolysis-targeting chimera (PROTAC) technology for protein degradation of KAT2A in acute myeloid leukaemia – a novel therapeutic approach

Patient perspectives on the discontinuation of bevacizumab: results from a qualitative embedded study within VALTIVE1, an advanced ovarian cancer biomarker study

Validation of Tie2 as the first tumour vascular response biomarker for VEGF Inhibitors: VALTIVE1

Understanding the variation of modern endoscopic ultrasound use in patients with oesophageal cancer (VALUE): a multi-methods study

Early Phase Clinical Trial Patient Experience

Katie Gilmour

Questionnaire – Decision making and decision fatigue

24/T46 Velindre Cancer Centre

Julie Graham

Research staff, who are we?

24/T47

Velindre University NHS Trust

Claire Lang

Upskilling the workforce to deliver Advanced Therapy Medicinal Products (ATMPs) to Cancer Patients across multiple sites – an Agile workforce.

24/T48

Velindre University NHS Trust

24/T49 Cardiff University

Amanda Jackson

Successful screening for Clinical Trials, what does it look like?

Malavika Babu

Examining the pattern of Demographic Factors and Bone Marrow Transplant requirement at Randomisation: Insights from the NCRI AML 18 Randomised Trial

CReSt Theme 5: Palliative and supportive oncology

24/T51

Cardiff University

Jane Hopkinson

24/T52

Cardiff University

Michelle Edwards

24/T53

Cardiff University

24/T54

Cardiff University

Michelle Edwards

Dr Daniella HollandHart

Nutritional care of people with colorectal cancer receiving non-surgical treatment

A rapid realist review: How do shared decisionmaking approaches, decision aids and communication tools influence the experience of making decisions about palliative treatments and supportive care for patients with advanced (noncurative) cancer?

Patient and Public Involvement in a Pan European Palliative Care Study: the Serenity study PPI protocol

Information and communication needs of patients with advanced incurable cancer and their caregivers: A rapid review

24/T55

Velindre Cancer Centre

Elin Harding

Are QR code wristbands acceptable to cancer patients receiving palliative intent oncology treatment?

CReSt Theme 6: Population health-based cancer prevention and early detection

24/T61

Cardiff University

24/T62

Cardiff University

24/T63

University Hospital of Wales, Cardiff

Pamela Smith

24/T64

Cwm Taf Morgannwg University Health Board, South Wales

24/T65

Cardiff University

Harriet QuinnScoggins

Feasibility of a Targeted Intensive Communitybased campaign To Optimise vague Cancer (TICTOC) symptom awareness and help-seeking in an area of high socioeconomic deprivation

The Yorkshire Enhanced Stop Smoking (YESS) study: process evaluation of a personalised intervention to support smoking cessation within lung cancer screening

Dr Tom Pembroke Evaluating our evolving HCC service

Optimising uptake of the Lung Health Check

Chris Coslett

Dr Pamela Smith

Operational Pilot within a socioeconomically deprived area of Wales

How might the provision of smoking cessation services be adapted to improve uptake and success for people in low socioeconomic groups? A mixed-methods exploratory study (PROCESS Study)

24/T66

Cardiff University/Cardiff and Vale University Health Board

Dr Andreia De Almeida

Early Detection and Diagnosis Marker Identification in Renal Cell Carcinoma: A Spatial Transcriptomic Approach

Novel agents for positron emission tomography (PET) imaging and targeted drug delivery to αvβ6-positive tumours

Emma A. Swift (1), Stephen J. Paisey (2), Toby J. Phesse (3), John F. Marshall (4), Pierre J. Rizkallah (5), Alan L. Parker (1), Rebecca Bayliss (1)

1

Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

2.

Wales Research and Diagnostic Positron Emission Tomography Imaging Centre, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

3.

European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK

4.

Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK

5.

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

αvβ6 integrins are minimally expressed on the healthy human epithelium, whilst being upregulated in several aggressive epithelial cancers. This marks them out as a favourable target for the development of diagnostic agents and anti-cancer therapeutics. Several classes of biologic capable of selectively recognising this integrin are under investigation, including short peptides and monoclonal antibodies. We sought to compare the in vivo biodistributions of three of these agents, comprising the foot-and-mouth disease virus-derived A20 peptide, antiαvβ6 monoclonal antibody 620W.7, and knob domain of the Ad5NULLA20 oncolytic virotherapy platform.

Agents were labelled with the long half-life radiotracer 89Zr via a bifunctional deferoxamine chelator. Radiochemical yields of >90% were achieved for all three classes of biologic Tracers were subsequently injected into the tail veins of CD-1 nude mice bearing αvβ6-positive A375-β6 and αvβ6-negative A375 tumours on opposite hips.

Longitudinal positron emission tomography imaging performed immediately after and at 24, 48, 72 and 144h (antibody group only) post-injection revealed selective trafficking of the 620W.7 antibody and A20 peptide complexed with streptavidin-89Zr to tumours expressing the αvβ6-integrin. Off-target uptake was restricted to the liver and spleen or kidneys respectively. In contrast, rapid bowel-mediated excretion of Ad5.KO1.A20 precluded its accumulation in αvβ6-expressing tumours

These results help to elucidate the distinct biodistribution and pharmacokinetic profiles of three different classes of αvβ6-targeted agent. In particular, the A20-streptavidin-89Zr complex demonstrated a highly promising positive: negative tumour uptake profile across all timepoints investigated and has the potential to act as a novel diagnostic imaging or selective-drug delivery tool.

Funding acknowledgement: Innovation for All Scheme

Clinical Application of Antibody Drug Conjugates and Exosomes as Advanced Therapeutics for Ovarian Cancer

Dr Claire Donnelly (1), Professor Deya Gonzalez (1), Professor Steve Conlan (1), Dr Jezabel Garciaparra (2), Dr Liliana Ordonez (3), Dr Lavinia Margarit (4), Dr David Howard (1)

1

Swansea University

2. University of the West of England Bristol

King Abdullah University of Science and Technology

3. Cwm Taff University Health Board

4.

Ovarian cancer (OC) has the highest mortality rate of all gynaecological cancers, with a low 5-year survival rate. This is in part due to resistance to chemotherapy drugs and recurrence,

which causes OC treatments to become inadequate. There is a critical need for novel therapeutic options that can enhance survival rates for OC patients.

Antibody drug conjugates (ADCs) are a type of targeted immunotherapy which takes advantage of the specificity of a monoclonal antibody and the potent cytotoxic effects of a small molecule drug, this results in highly specific treatment with fewer off target toxic effects due to targeting a carefully selected surface protein, highly expressed in cancer cells compared to healthy cells.

Exosomes are a type of extracellular vesicle (EV), which contain proteins, lipids and nucleic acids derived from their parental cell. Exosomes are key moderators of intercellular communication through the transfer of cargo between cells. The exosomal cargo varies depending on type and state of cell of origin. This leads to the involvement of exosomes in many physiological processes such as immune responses However, exosomes derived from tumour cells are implicated in pathological processes, such as cancer progression

Both ADCs and exosomes were investigated as advanced therapeutic options for OC, in addition the biomarker potential was explored

Funding acknowledgement: WCRC

Machine Learning and response to induction chemotherapy in patients with Acute Myeloid Leukemia

Heba Elhaddad (1,2,3) Claudia Chiriches (1,2), Katie Watts (5), Peter Giles (4), Amanda Gilkes (1,2), Martin Ruthardt (1,2)

1.

Division of Cancer and Genetics, Section of Hematology, School of Medicine, Cardiff University, Cardiff, UK

2.

Experimental Cancer Medical Centre (ECMC) Cardiff, School of Medicine, Cardiff University, Cardiff, UK

3.

4

Faculty of Medicine, Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.

Wales Gene Park, Henry Welcome Building, Cardiff University, Cardiff, UK

5.

Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.

Background: Until now, no validated scoring system has accurately predicted patients’ responses to chemotherapy Most prediction approaches are complicated as they utilize various cytogenetic and molecular abnormalities. Random Forest (RF) is a machine learning algorithm widely used to make predictions related to cancer. RF has recently been applied to predict AML patients’ overall survival (OS). The algorithm demonstrated a prediction efficiency of AUC 0.59 to 0.64, better than the ELN risk stratification. Based on these results, we have decided to implement the RF algorithm in predicting the response of AML patients to induction chemotherapy (IC)

Method: Our study included 111 gene-targeted sequencing data of a cohort of 1552 AML patients from the AML NCRI study group. Following intense IC, patients were stratified into responders achieving complete remission (CR) or resistant not achieving CR. The CR rate in our dataset was around 80%; however, 47% of these patients relapsed during follow-up. The cohort was randomly split into training (70%) and test (30%) sets. Our dataset was highly imbalanced (80% CR vs. 20% resistance). Therefore, the training set was balanced using SMOTE before RF analysis

Results: Different relapse time thresholds were initially tested to decide whether to include the relapsed patients in the CR or the resistant group. RF revealed that the best prediction accuracy could be obtained when all relapsed patients were included in the CR group RF model built with a balanced training set efficiently predicted the outcome of the test set with 79% accuracy, AUC 0.676, 87% sensitivity, 44% specificity, 86% positive predictive value (PPV), and 46% negative predictive value. The SMOTE balancing technique improved the prediction efficiency of the test set. This was evident in the increase of accuracy and specificity to 79% and 44%, respectively, in the balanced model compared to 73% and 19% in the unbalanced model

Conclusion: RF is a practical, rapidly developing algorithm that can be incorporated into future technologies to obtain high response prediction accuracy in AML patients.

Funding acknowledgement: Newton Musharafa and Central department of Missions Egypt

Enhancing Structural Variant Detection and Visualization in Cancer

Genomics: Integrated Approaches with Dysgu and GW

Kez Cleal (1), Alexander Kearsey (1), Emmon Croot (1), Duncan Baird (1)

Division of Cancer and Genetics, Cardiff University 1.

Recent advances in genomics have underscored the importance of structural variation (SV) in cancer biology. Accurate detection and efficient visualization of these variants are crucial for understanding cancer development and progression. Our previous work introduced 'dysgu', a tool for calling SVs using paired-end or long-read sequencing data with high sensitivity and precision. We have enhanced dysgu by developing a new tumour-normal filtering pipeline for cancer SV detection, suitable for use in a clinical setting and tailored to cancer genome landscapes We benchmarked our approach using publicly available datasets, and report best-in-class results

Complementing this, our latest development 'GW', an ultra-fast genome browser, addresses the challenges in visualizing large genomic regions in cancer genomics. GW's design focuses on speed and memory efficiency, and enables >100-fold increase in speed for exploring large variants and genomic regions, scaling to entire chromosomes. GW implements a novel approach for presenting variants as interactive thumbnail image-tiles which facilitates faster dataset exploration and curation.

We present an integrated approach combining dysgu's enhanced SV detection with GW's optimised visualization capabilities, enabling accurate detection, visualization and curation of SVs on a genome-wide scale. The integration of these tools offers scalable solutions for variant detection and visualization in cancer genomic research.

Final results and performance metrics will be presented, showcasing the potential of this integrated approach for cancer genomic research and clinical diagnostics, particularly for SV discovery and reporting in cancer genomics services

Funding acknowledgement: CRUK, WCRC

24/T15

High-resolution telomere analysis for clinical diagnostics

Kevin Norris (1,2), Duncan M. Baird (1)

1.

TeloNostiX Ltd, 30-36 Newport Road, Cardiff, UK.

2.

Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.

STELA (Single Telomere Length Analysis) is a high-resolution approach to determine telomere length (TL) distributions. Despite the high accuracy of the method, STELA is labour intensive and low throughput, meaning it is unsuitable for clinical laboratory applications. To overcome these limitations HT-STELA (High Throughput-STELA) was developed which provides accurate and robust TL analysis within 2 days of sample collection from the patient, making the method highly applicable as a clinical assay The technology was licenced to TeloNostiX, a Cardiff University spin-out company, that has developed HT-STELA into an ISO17025 accredited clinical laboratory service used by NHS centres across the UK, as well as multiple centres in the EU, New Zealand and Australia.

HT-STELA analysis of large patient sample cohorts and has revealed powerful prognostic and predicative signatures chronic lymphocytic leukaemia (CLL) and this work is being extended to other tumour types including Glioblastoma and Head & Neck cancer.

HT-STELA is used for routine clinical diagnosis of patients with telomere biology disorders (TBDs), conditions that arise due to mutations in genes required for telomere maintenance. The utility of TL in the diagnosis of interstitial lung disease (ILD) is currently being explored with the hope of providing a clinical diagnostic service for ILD in the same manner as for TBDs patients.

Further development of the HT-STLEA technology allows for a TL profile to be generated from dried blood spot DNA thus facilitating at home patient sample collection and potentially allow for larger-scale population studies. Recent data illustrating the use of HT-STELA for clinical applications will be presented

Key cell survival mechanisms allow KrasG12D cells to be retained in the competitive tissue environment of the adult pancreas.

Beatriz Salvador-Barbero (1), Markella Alatsatianos (1), Jennifer Morton (2), Owen Sansom (2), Catherine Hogan (1)

1. Cancer Research UK Beatson Institute, Glasgow, UK

European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, UK.

2

Pancreatic ductal adenocarcinoma (PDAC) arises and expands from epithelial cells carrying activating mutations in oncogenic KRAS PDAC is a devastating disease with poor prognosis, primarily because diagnosis occurs at late and incurable stages. A better understanding of the biology of early disease is urgently required to improve early detection and patient outcomes. We use the KC mouse model of pancreatic cancer (Pdx-1 CreERT LSL-KrasG12D/+; Rosa26 LSL-tdRFP) to study the biology of early sporadic tumorigenesis in adult pancreas in vivo. Our research shows that when present in tissues in low numbers, cells expressing oncogenic KrasG12D compete with normal cells for survival and are often eliminated. Cell elimination prevents the development of premalignant lesions in tissues, suggesting competition in the tissue is tumour suppressive. In general, we lack information on how genetically mutant cells grow in healthy tissues. Our research suggests mutant cells must override elimination signals to survive in a competitive tissue environment Remarkably, we find that some KrasG12D cells are never eliminated, suggesting this population of mutant cells has a competitive advantage. RNA sequencing of noneliminated KrasG12D cells shows a downregulation of apoptosis and an upregulation of pathways associated with ‘winner’ status. Using cell competition assays in vitro and pharmacological inhibition in vivo, we demonstrate the requirement of key cell survival signals in the control of KrasG12D cell fate. An improved understanding of these initial steps, when mutant cells are positively selected in a tissue, may inform early detection cancer strategies.

Funding acknowledgement: Cancer Research UK (CRUK)

Preclinical evaluation of a novel antibody drug conjugate for prostate cancer

Daniel Turnham (1), Liliana Ordonez (2), Anna Richards (1), Stephen Paisey (3), Sam Mitchell (2), Deyarina Gonzalez (2), Steven Conlan (2), Helen Pearson (1)

1

European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, UK

2.

Reproductive Biology and Gynaecological Oncology Group, Institute of Life Science 2, Swansea University Medical School, Swansea University, Swansea

3.

PETIC, School of Medicine, Cardiff University, Cardiff, Wales, UK

Globally, prostate cancer (PCa) is the second most common male malignancy and remains one of the leading causes of cancer-related deaths. Although treatment options have improved, survival remains poor (often less than 2-years) for metastatic-PCa (mPCa), emphasising the unmet clinical need for new efficacious therapies, particularly for untreatable chemo-refractory/castrate-resistant disease Antibody-drug conjugates (ADCs) have emerged as an exciting therapeutic strategy owing to their unique ability to specifically target malignant cells for cytotoxic killing without damaging healthy normal cells. Several ADCs have now been clinically approved to treat different cancer types, including PSMA-targeted therapies for mPCa which have significantly improved survival rates Despite this, not all patients are eligible for treatment while remission is often short-lived in those who do respond well. Accordingly, the development of a broad range of ADCs, with distinct toxic payloads, is essential to offer further treatment options and improve survival rates.

To this end, we have developed a new potent ADC targeting the receptor-for-advanced-glycation-end-products (RAGE), that delivers cytotoxic drugs specifically to PCa cells expressing RAGE. Importantly, up to 90% of mPCa cases express RAGE, thus presenting a therapeutic strategy that could benefit many patients. Here we demonstrate how chimeric RAGE-targeting ADCs can efficiently bind, internalize and kill RAGE-positive PCa cell lines in vitro and effectively target RAGE expressing PCa cells in vivo to inhibit tumour growth. Interestingly, our data suggests that combining RAGE-ADC treatment with docetaxel, a chemotherapy routinely used to treat patients with mPCa, can offer improved therapeutic responses in vivo. Finally, we highlight the potential of using radiolabelled RAGE antibodies as a diagnostic tool to detect PCa’s that are likely to benefit from RAGE-targeted therapy Together this data provides evidence that RAGE could be used as a theranostic target, to diagnose and treat aggressive, hard-totreat PCa clinically in the future.

Mechanisms underlying the required expression of S100A4 for proliferation and survival of AML blasts

Alanazi, Rehab N (1,2), Rizzo, S (1), Gilkes, A (1), Knapper, S (1,3), Darley, RL (1), and Tonks, A (1)

1.

Department of Haematology, Division of Cancer & Genetics School of Medicine, Cardiff University, Cardiff, UK

2 Cardiff Experimental and Cancer Medicine Centre, School of Medicine, Cardiff University, Cardiff, UK.

Medical Laboratory Technology Department, College of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia

3.

Acute myeloid leukaemia (AML) is characterized by the uncontrolled proliferation of myeloid precursor cells in the bone marrow. Our previous study identified S100A4 as being upregulated in the nuclei of AML blasts from 11 out of 15 patients, with an average 5.5-fold increase compared to controls. S100A4 is a calcium-binding protein that regulates cell proliferation and survival, however its role in AML was not well defined. In this study, we aimed to elucidate the effects of S100A4 on AML cell growth and survival through genetic knockdown and transcriptomic analysis.

Lentiviral vectors expressing short hairpin RNAs (shRNAs) targeting S100A4 were used to knockdown S100A4 expression in AML cell lines THP-1, NOMO-1, TF-1 and OCI-AML2 Infection efficiencies exceeding 95% were achieved, with cells remaining viable. Knockdown of S100A4 protein expression was confirmed by Western blot. Flow cytometry revealed significantly reduced cell growth and survival upon S100A4 knockdown. However, no effects were seen in KG1a cells which have undetectable S100A4 expression.

To understand the mechanisms underlying S100A4's effects, mRNA sequencing will be performed to compare the transcriptomes of S100A4 knockdown cells versus controls. This provides a global view of the pathways regulated by S100A4 in AML. High quality RNA has been extracted and assayed to confirm suitability for sequencing. Bioinformatic analysis was identify differentially expressed genes and affected pathways.

In summary, genetic knockdown of S100A4 significantly reduced AML cell growth and survival, indicating it may be a promising therapeutic target Transcriptomic profiling will elucidate the molecular mechanisms through which S100A4 exerts its oncogenic effects in AML.

Funding acknowledgement: Northern Border University, Saudi Arabia

Manipulating T-cell immune responses in order to improve antiGlioblastoma immunity

Mathew Clement (1), Michael Somerville (2), Florian Siebzehnrubl (2), Awen Gallimore (1)

1.

Division of Infection and Immunity, Cardiff University

European Cancer Stem Cell Research Institute, Cardiff University 2

Glioblastoma (GBM) is the most common form of primary brain cancer which spreads throughout the brain. It remains incurable and is one of the worst survivable cancers. This fatal disease can occur at any age but is most commonly found in adults and is more prevalent in older men Treatment options include surgery (if available), temozolomide chemotherapy and radiotherapy. Post treatment, GBM tumours return highlighting the critical need for new therapies.

Current therapeutic approaches for GBM largely fail to prevent relapse due to genetic and cellular heterogeneity within the tumour. Whilst tumour infiltrating T-cells express immune checkpoint inhibitors including LAG3, PD-1 and CTLA4, immunotherapeutic targeting of these has failed to promote control of GBM, indicating that other targets are needed. The immune-modulating cytokine IL-10 plays a major role in promoting an immune-suppressive tumour microenvironment (TME), and has been shown to promote tumour progression CD4+ T-cells are known to release IL-10 (TH1, TH2 and Regulatory T-cells) during inflammation, however, the direct association of IL-10 production by T-cells contributing to the immune-suppressive environment in GBM remains unknown.

My preliminary results show that IL-10 is over-produced in a mouse model of GBM. These findings have provided me with the opportunity to test whether IL-10 represents an effective target for intervention where blocking IL-10 with antibodies may unleash effective immune responses capable of killing GBM cells. The data shown here describes how IL-10 suppresses the effector functions of tumour-specific T-cells in the GBM TME and how novel invasive and non-invasive therapies will be designed that target IL-10 to improve anti-GBM immunity.

Funding acknowledgement: Wales Cancer Research Centre / Systems Immunity Research Institute

Developing a 3D colorectal organoid/T cell co-culture model to test cancer immunotherapeutics

Stephanie Burnell (1), Lorenzo Capitani (1), Julia Grimstead (2), Sara Seifan (2), Duncan Baird (2), Kasope Wolffs (1,3), Fiona Morgan (3), Paola Foulkes (3), Luned Badder (2), Alan Parker (2), Andrew Godkin (1, 4), Awen Gallimore (1)

Division of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK 1

2.

Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

3.

Wales Cancer Biobank, UHW Main Building, Heath Park, Cardiff, CF14 4XN, UK

4.

Department of Gastroenterology and Hepatology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK

Developing organoids as a 3D model system which maintains original tissue architecture and composition is a game changer in cancer research. Within this project, funded by Wales Cancer Research Centre, we aimed to go a step further and develop a co-culture system that recapitulated the colonic structure and incorporated T cells to test new immunotherapies.

With a pipeline of colorectal cancer (CRC) patient identification and consent in place, we have amassed a large bank of matched healthy and tumour organoids with matched peripheral blood mononuclear cell samples Working with this material, we have used a machine learning approach to develop computational tools for estimating cell numbers within organoid culture, which will be released as a web interface for other organoid users in the near future. This tool has been essential for the optimisation and development of imaging methods for assessing the behaviour of T cells in organoid co-culture systems. Using live cell imaging methods, we can visualise and measure these interactions over time. This 3D in vitro model is poised to act as a test bed for our in-house immunotherapeutics, including engineered T cells and small molecule inhibitors, in addition to investigations into the tumour microenvironment.

Funding acknowledgement: Wales Cancer Research Centre

24/T23

Generating hexon chimeric adenoviruses designed to circumvent neutralising anti-vector immunity

R Wallace (1), C M Bliss (1,2), A L Parker (1,2)

Division of Cancer & Genetics, Cardiff University School of Medicine

1. Systems Immunity URI, School of Medicine, Cardiff University, Cardiff 2

As oncolytic viruses (OV), the species C human Adenovirus (Ad), Ad5 has proven popular due to its high lytic activity and the relative ease with which it can be manipulated. We previously developed the Ad5NULLA20 vector, which is effectively retargeted to αvβ6 integrin, which is absent on healthy tissue but highly expressed in many aggressive epithelial cancers. However, pre-existing immunity against Ad5 limits the current potential of Ad5 based OVs. Species D Ads have low pre-existing population immunity, representing a relatively untapped repository. Phylogenetically, species D Ads encompass the largest and most diverse species of Ad and might therefore be good alternative oncolytic platforms

We used recombineering to create various hexon-chimeric Ad5 based genomes, with parts of the highly immunogenic hexon protein's Hypervariable Regions (HVRs) exchanged for those of less common serotypes. Selected constructs were based on dissimilarity in sequence and similarity in size to Ad5HVRs Structural models were designed using I-Tasser, YASARA energy minimisation and PyMOL. Rescue of recombinant viruses was attempted using transfection of T-Rex293 or 293-B6 cells.

We successfully generated a number of viable Ad5 and Ad5.A20 based viral vectors containing HVR swaps from species D, and are presently assessing their ability to transduce cells in the presence of neutralising anti-Ad5 antibodies.

Whole hexon swaps have previously proven non-viable for our chosen serotypes, whilst exchanging single HVRs appears viable. We hope this will allow us to create viral vectors capable of evading host immunity, enhancing the activity of oncolytic virotherapies in patients with pre-existing anti-Ad5 immunity.

“Precision Immunovirotherapies” expressing bispecific immune cell activators induce immune cell activation and tumour cell killing

Rebecca J. Bayliss (1), Luned Badder (1), Simon Kollnberger (2), James A. Davies (1), Awen M. Gallimore (2), Alan L. Parker (1)

1.

Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK

2.

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK

We previously described the construction of a highly engineered, tumour-selective virotherapy, Ad5NULL-A20, able to infect cancerous cells via αvβ6 integrin expressed in multiple aggressively transformed epithelial cancers. To enhance the activation of tumor infiltrating T-cells and Natural Killer cells to control tumor growth we engineered the Ad5NULL-A20 platform to express bi-specific molecules targeting either CD3 (T-cells) or CD16 (NK cells), and the tumour-antigen Epidermal growth factor receptor (EGFR) to encourage immune cell activation and redirect an effective immune response to tumour sites.

Incorporation of bispecific immunotherapies did not alter infectivity nor oncolytic activity of the viruses and secretion of bispecific molecules was evident by Western blot. EGFR positive cells co-cultured with NK cells in the presence of virally infected supernatants containing the CD16-EGFR targeting bispecific significantly increased cytotoxic NK cells. Similarly, CHO-EGFR cells co-cultured with a T-cell reporter cell line in the presence of CD3-EGFR supernatants saw an increase in GFP expression representing the upregulation of NF-κB signalling and T-cell activation. Assays using cancer cell lines and healthy donor CD3+ T-cells saw a significant increase in CD4+ and CD8+ T-cell activation, intracellular IFN-γ production and proliferation in cancer lines infected with Ad5NULL-A20 secreting CD3-EGFR bispecific constructs. NK cell cytotoxicity, TNFα and IFN-γ expression was increased in cells secreting CD16-EGFR bi-specifics. All constructs induced immune mediated cancer killing between 1-5days of coculture. Furthermore, patients derived pancreatic organoids infected with Ad5NULL-A20 oncolytic viruses expressing CD3-EGFR and CD16-EGFR show immune mediated cell killing of cancerous cells as early as 48 hours coculture. Data suggests viruses containing the bispecific molecules are effective at inducing a immune response at tumour sites resulting in immune mediated killing of tumour cells in vitro.

We demonstrate the arming of a tumour selective agent, Ad5NULL-A20 to express bispecific immune cell engagers designed to immunologically “heat up” the Tumour Microenvironment This approach has significant translational potential.

Funding acknowledgement: Cancer Research UK/Stand up to Cancer

ABC-12: Exploring the microbiome in patients (pts) with advanced biliary tract cancer (BTC) in a first-line study of durvalumab in combination with cisplatin/gemcitabine (cis/gem)

Hayley Timmins (1), Ashley Osborne (2), Rebecca Cox (2), Joanna Canham (1), Muhammad Riaz (1), Charlotte Martin (1), Harpreet Wasan (3), Pippa Corrie (4), Roopinder Gillmore (5), Shivan Sivakumar (6), Olusola Faluyi (7), Arvind Arora (8), Seema Arif (9), Elizabeth Smyth (10), Richard A Hubner (2), John Bridgewater (11), Richard Adams (1,9), Juan W Valle (12,2,13), Mairéad G McNamara (12,2)

2.

3. Imperial

4. Cambridge

Hospitals NHS Foundation Trust 5 Royal Free London NHS Foundation Trust 6 University Hospitals Birmingham NHS Foundation Trust 7. Clatterbridge Cancer Centre NHS Foundation Trust 8. Nottingham University Hospitals NHS Trust 9.Velindre University NHS Trust 10. Oxford University Hospitals NHS Foundation Trust 11. University College London Hospitals NHS Foundation Trust 12. University of Manchester 13. The Cholangiocarcinoma Foundation

Background: Durvalumab/cis/gem improved overall survival (OS) in pts with advanced BTC versus placebo/cis/gem (Oh et al. NEJM Evid 2022). Disruption of the microbiota may impair tumour response to immunotherapy/chemotherapy; a better understanding of its role in efficacy of these therapeutics in advanced BTC is required.

Methods: This is a multi-centre, single arm trial, recruiting 70 pts from 10 sites to explore the microbiome in pts receiving durvalumab 1500 mg intravenously (IV) Q3w, in combination with cis 25 mg/m2, gem 1000 mg/m2 (Days 1 and 8, Q3w) up to 8 cycles, followed by durvalumab 1500 mg as monotherapy Q4w, until progression or intolerable toxicity. Pts with an ECOG PS of ≤1, histologically-proven BTC, including cholangiocarcinoma and gallbladder carcinoma, with no prior systemic chemotherapy for locally advanced or metastatic disease are eligible Pts must provide a saliva and stool sample before durvalumab/cis/gem and at 18 weeks, or at progression (if earlier than 18 weeks). Taxonomic profiling via 16S Ribosomal ribonucleic acid gene sequencing will examine differences in diversity and composition of the gut microbiome. The primary objective is to determine the difference in baseline alpha diversity between “responders” (partial/complete response) and “non-responders” at 18 weeks (RECIST 1 1) Secondary objectives include investigation of association between microbiome parameters and objective response rate, tumour control (partial + complete response + stable disease), progression-free and OS, and investigate interaction between treatment effect and microbiome parameters. Archived tissue will be used for research into the tumour microbiome and/or factors that may influence response to chemotherapy/immunotherapy

Funding acknowledgement: AstraZeneca

1. Cardiff University

The Christie NHS Foundation Trust

College Healthcare NHS Trust

University

Assessment of a pre-clinical viral-vectored cancer immunotherapy designed to harness anti-viral immunity against cancer cells

Kate Milward (1), Aimee Lucignoli (1), Katie Topley (2), Elise Moses (1), Garry Dolton (2), Lucy C Jones (2,3), Andrew Sewell (2), Carly M Bliss (1,4), Alan L Parker (1,4)

1.

Division of Cancer & Genetics, Cardiff University

2. Cwm Taf Morgannwg University Health Board

Division of Infection & Immunity, Cardiff University

3.

4

Systems Immunity Research Institute (SIURI), Cardiff University

Cancer immunotherapy strategies are being explored to induce, engineer, or target potent immune responses against cancer. We aimed to test the effectiveness, and specificity, of a novel adenoviral-vectored immunotherapy, designed to harness anti-viral immunity and re-direct this activity towards tumours

The vector utilises a well-characterised, non-replicating Adenovirus type-5 (Ad5) platform, Ad5NULL-A20. The Ad5 NULL modifications eliminate native Ad5 tropisms towards healthy tissue. Meanwhile, the A20 peptide confers tumour-tropism, re-targeting viral entry via αvβ6, an integrin that is highly enriched on several epithelial cancers but not expressed on healthy adult epithelium. The vector additionally encodes, a common viral antigen (VA), against which a large proportion of the population exhibit cytotoxic T-cell immunity through vaccination/infection. We hypothesise that this adenoviral therapy would drive cancer cell presentation of immunogenic viral peptides, ultimately targeting those cells for destruction by VA-specific T cells.

After screening an array of cancer cell lines by flow cytometry, we composed panels of cell lines representing different levels of αvβ6 expression, and different HLA (Human Leukocyte Antigen) types Following infection with Ad5 NULL -A20.VA in vitro, we quantified surface expression of vector-encoded VA, and of native HLA, in infected versus uninfected cancer cells. Further, we assessed the activation of VA-specific T cells co-cultured with cancer cells.

Preliminary results indicate VA-specific T cells were activated in the presence of cancer cells transduced with Ad5 NULL -A20.VA, in an αvβ6- and HLA-dependent manner. These findings suggest that Ad5 NULL -A20.VA can preferentially target αvβ6-expressing cancer cells and induce VA-reactive T cell activity.

Funding acknowledgement: Wales Cancer Research Centre; Cancer Research UK; Life Science Hub Wales

Delivery of suicide therapies using a precision virotherapy; novel approaches for pancreatic cancer

Luned M. Badder (1), James A. Davies (1), Beatriz Salvador-Barbero (2), Mahulena Marušková (1), Valerie S. Meniel (2), Carly M. Bliss (1), Rebecca J. Bayliss (1), Toby Phesse (2), Catherine Hogan (2), Alan L. Parker (1)

1.

Division of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, Wales

2.

European Cancer Stem Cell Research Institute (ECSCRI), School of Biosciences, Cardiff University, Wales

Pancreatic ductal adenocarcinoma (PDAC) lack validated therapeutic targets and represent an unmet clinical need We have previously described a tumour-selective adenovirus based virotherapy, Ad5NULL-A20, capable of entering cells via αvβ6 integrin. Given that αvβ6 integrin is strongly expressed in PDAC, with limited expression in healthy adult epithelium, it is a highly attractive therapeutic target. Here, we aim to enhance the potency of Ad5NULL-A20 by incorporating “suicide transgenes” capable of eliciting toxicity in PDAC cells

We successfully generated replication-deficient Ad5NULL-A20 vectors expressing either yeast cytosine deaminase (CD;FCY1) or a fusion of CD and uracil phosphoribosyltransferase (FCU1), which converts a non-toxic pro-drug 5fluorocysteine (5-FC) to the cytotoxic chemotherapeutic 5-fluoruracil (5-FU) and associated toxic metabolites (5FUMP), respectively. Our data demonstrate that Ad5NULL-A20.FCY1 and Ad5NULL-A20.FCU1 selectively sensitise αvβ6+ pancreatic cancer cells to 5-FC. Overall, the FCU1 transgene causes the highest levels of cell killing, with log-fold changes in IC50 values compared to FCY1. Ad5NULL-A20.FCU1-mediated conversion of 5-FC to 5-FU and 5FUMP further elicited toxicity to neighbouring cells in vitro by means of a bystander effect in naïve CFPAC1 (αvβ6+) pancreatic cancer cells. We used clinically-relevant 3D organoid cultures from a mouse model of PDAC (KPC;Pdx1CreERT LSL-KrasG12D/+; LSL-Trp53R172H; Rosa26LSL-tdRFP) and found a strong sensitivity to 5-FC in organoids infected with Ad5NULL-A20 FCU1 Patient-derived PDAC organoids were found to be highly sensitive to 5-FC treatment following Ad5NULL-A20.FCU1 infection.

Taken together, these data highlight a novel Virus-directed enzyme prodrug therapy (VDEPT) with high selectivity and toxicity in PDAC that could potentially bypass systemic toxicity associated with chemotherapeutics, supporting future clinical translation of this platform.

Funding acknowledgement: Cancer Research Wales, Cancer Research UK

24/T31

Development of a Radiotherapy Dashboard

Radiotherapy Physics Service, South West Wales Cancer Centre, Swansea Bay University Health Board 1.

This project outlines the development of a live Radiotherapy Dashboard. Using live data extraction from the Oncology Management System, we are able to analyse every step of the Radiotherapy Treatment Planning stages by tumour site to identify bottlenecks, and staff resources required for each stage.

The dashboard has help develop the case for advanced non-medical roles, ensure minimum numbers are completed by individual staff, to ensure they attain and maintain competence, and optimise resource allocation The dashboard is also able to identify individual patients waiting too long, and those nearing a breach date. The techniques used can be applied to other centres.

Funding acknowledgement: DCHW Big Data Fund

Ryan Lewis (1), Christopher Rose (1), Douglas Etheridge (1), James Jenkins (1)

24/T32

Developing the role of radiotherapy for inoperable gastric cancer

1. Swansea University Medical School

South West Wales Cancer Centre, Swansea Bay University Health Board

2.

3 Cardiff University

Cwm Taf Morgannwg Health Board

4. Velindre Cancer Centre

5.

Gastric cancer (GC) is one of the “Less Survivable Cancers” in Wales, with a 5-year overall survival (OS) of 18 2%, emphasising the urgent need for new treatment strategies. The role of radiotherapy for inoperable GC has not been fully investigated, which we endeavoured to address.

A systematic review evaluating the role of definitive radiotherapy for GC was conducted Nine single-arm studies (n=294 patients) were identified, reporting clinical complete response (cCR) rate of 8-45% and median OS of 11-26.4 months - prolonged to up to 30.7 months if cCR achieved, supporting additional research.

To gauge clinician opinion, we undertook a survey of 43 UK-based Consultant Clinical Oncologists specialising in GC. Although currently only 28.6%, 7.1% and 9.5% would consider radiotherapy as a treatment option postoperatively, pre-operatively or definitively respectively, 76.6% support the development of further clinical trials.

To investigate the optimal approach to gastric tumour volume delineation (TVD), we performed a study evaluating the role of magnetic resonance imaging (MRI) in addition to computed tomography (CT) on interobserver variation. Of 19 observers who completed 1 of 2 test cases, MRI improved ease of TVD in 72.7-90%. Although for case 1, conformity improved with addition of MRI (Jaccard Conformity Index= 0.66 CT vs 0.71 CT+MRI), it worsened for case 2 (JCI = 0 88 vs 0 83), demonstrating the necessity for further studies and education

Collectively, this research has informed, and continues to shape the design of GastroSCOPE – the first UK clinical trial to investigate the role of high-dose palliative radiotherapy for inoperable GC.

Funding acknowledgement: Wales Cancer Research Centre, South West Wales Cancer Fund, Swansea Bay University Health Board.

A. Case (1,2), H. Hutchings (2), S. Prosser (1), B. Slinger (1), K. Foley (3,4), E. Spezi (4), G. Joseph (5), T. Crosby (5), O Nicholas (1,2), J Helbrow (1), R Adams (4,5), S Gwynne (1,2)

Identifying and addressing barriers to clinical oncology trainees’ involvement in radiotherapy research in Wales

Shannon Rowlands (1), Richard Adams (2,3), Sarah Gwynne (1,4)

1

Swansea University

Velindre Cancer Centre 2.

Cardiff University 3.

South West Wales Cancer Centre 4.

The Cancer Research Strategy in Wales identifies the need to improve delivery and accessibility of cancer research, with clinical teams being key.

Identifying opportunities and challenges for teams in Wales has never been more important with the decline in numbers of academic clinical oncologists alongside an increase in clinical oncology training posts. Improving radiotherapy (RT) research within the training programme could create a stronger future for research in Wales.

Methods: We surveyed 104 individuals working in RT across Wales, including 13 oncology trainees. On the basis of the results found we conducted a mini delphi exercise involving 13 research-active clinical oncology consultants and 11 trainees to define research competencies for a) all trainees and b) those with deeper interest in research.

Results: Trainees stated high clinical workload, lack of infrastructure, and failure to promote RT research as barriers to being more involved, with only 70% considering being involved in research as consultants, in spite of high levels of interest in research per se. The subsequent mini delphi identified mandatory (years 1-2 and 3-5) and optional competencies

Conclusion: In order to address the barriers identified by oncology trainees in Wales, we propose recommendations for competencies in research that are incorporated into the training programme, with appropriate provision to acquire them We believe these achievable changes will improve the accessibility of and engagement in RT research and build a research active consultant workforce for the future.

24/T34

Radiotherapy Systemically Alters the Immunological Landscape in Patients with Oligometastatic Cancer

Jessica Oliver (1), Hannah Reed (1), Thomas Rackley (2), Catherine Pembroke (2), Ashleigh Young (2), Andrew Godkin (1), Awen Gallimore (1)

Department of Infection and Immunity, Cardiff University 1. Velindre Cancer Centre, Cardiff 2.

The landscape of cancer treatment has evolved rapidly within the last 50 years Although radiotherapy, chemotherapy and surgery remain the mainstay treatments, there has been a shift towards the use of immunotherapy. There is current focus on the ability of radiotherapy to stimulate T cells to recognise tumour cells at distal sites to the treatment, inducing an immune-mediated anti-tumour effect termed the abscopal effect. This study explores the impact of stereotactic ablative radiotherapy (SABR) on immune composition and antigenspecific T cell responses.

Immune alterations were monitored throughout SABR treatment in patients with primary and oligometastatic cancers. Using diverse techniques such as Luminex, Flow Cytometry, and ELISpot assays, we identified striking systemic changes to the immune composition, T cell responses and plasma analytes during and after SABR.

Paradoxically, both immunostimulatory and immunosuppressive responses emerge following SABR Although T cellspecific responses in cancer patients and healthy donors are similar at baseline, recognition of control and tumour antigens is hindered during treatment. A significant predictor of post-treatment progression is an increase in neutrophil to lymphocyte ratio (NLR) during treatment. Patients who exhibited over a 20% increase in their NLR during treatment were more likely to progress Furthermore, we have shown that baseline plasma concentrations of inflammatory cytokines are associated with response to SABR.

Overall, we have observed significant radiotherapy-driven systemic immune changes, with distinctions between responders and progressors Further exploration is required to understand the mechanisms which account for these changes to identify opportunities for immunotherapy interventions to enhance responses to SABR.

A

Randomised Open Label Multicentre Phase III Clinical Trial Evaluating Adjuvant Radiotherapy in Patients with High-risk Primary Cutaneous Squamous Cell Carcinoma AFTER Surgery: SCC-AFTER Study Protocol

Ann White (1), Chloe Austin (1), Lisette Nixon (1), Lucy Marsh (1), Stephanie Coakley (1), Ceri Frayne (1), Catharine Porter (1), Angela Casbard (1), Victoria Shepherd (1), Julia Wade (2), Agata Rembielak (3), Catherine Harwood (4)

1

Centre for Trials Research, Cardiff University

University of Bristol 2. The Christie NHS Foundation Trust 3. The Royal London Hospital 4.

Background: The incidence of cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is increasing annually. Surgery cures 95%, however, 5% (high-risk T2b/T3 Brigham & Womens’ Hospital T-staging) develop loco-regional recurrence (LRR) accounting for 75% of cSCC-specific deaths and reduced quality of life (QoL). To reduce LRR, adjuvant radiotherapy (ART) is used inconsistently in NHS hospitals as standard of care. Due to a lack of randomised data, it is not well established if treating high-risk patients with ART leads to better outcomes. Feasibility surveys, simulated case-based discussions and a systematic review identified widespread but variable use of ART in UK practice. Establishing whether ART is clinically and cost-effective will be of benefit to patients and will inform clinical guidelines and healthcare policy.

Methods: This phase III randomised trial aims to recruit 840 participants across 25 UK sites over 4 years. Adult participants who have had a high-risk primary cSCC completely excised will be eligible Randomised 1:1 to either ART followed by close clinical follow-up (CCFU) or CCFU only for 3 years. LRR-free survival time will be measured to evaluate the primary objective of whether ART plus close clinical follow-up is more effective at reducing LRR than close-clinical follow-up. Qol, distant metastasis-free survival, overall survival, safety, and cost-effectiveness will be explored as secondary objectives The trial includes an integrated QuinteT Recruitment Intervention (QRI) with embedded INCLUSION ‘Study within a project’ (SWAP) to optimise recruitment and informed consent, particularly amongst patients historically underserved in trials, including those older, frailer, and immunocompromised.

Funding acknowledgement: National Institute for Health and Care Research

Proteolysis-targeting chimera (PROTAC) technology for protein degradation of KAT2A in acute myeloid leukaemia – a novel therapeutic approach.

Loren Waters (1), Darren LeGrand (1), Hitesh Patel (2), Andrea Gunnell (3), John Atack

1.

Medicines Discovery Institute, Cardiff University

2 Sussex University 3.

School of Biosciences, Cardiff University

Ward (1)

Acute myeloid leukaemia (AML) is an aggressive malignancy of white blood cells, where genetic alterations lead to defective differentiation of the blood cells, causing them to remain in an immature state The immature blast cells acquire abnormal progenitor self-renewal capacity that is maintained by a subpopulation known as leukaemic stem cells (LSCs). The LSCs sustain a proliferative state and thus cancer cell survival, which rapidly leads to AML progression and frequent drug resistance. Most cases occur in patients over 65 years old and this patient population struggles to tolerate the standard cytotoxic chemotherapy regimen required to reach remission of the disease, resulting in a poor prognosis of <30% survival 5-years post-diagnosis. The transcriptional activator lysine acetyltransferase 2A (KAT2A) has been implicated in the pathogenesis of AML. Through regulating a level of ‘transcriptional noise’ expressed in cell populations, this reinforces the LSCs undifferentiated and proliferative state. As such, the loss of KAT2A has been demonstrated to induce terminal differentiation of the LSCs population, which is critical towards patient relapse. Here, we present the promise for proteolysis-targeting chimera (PROTAC) technology – a targeted protein degradation system that exploits the cells own destruction machinery, to deplete KAT2A, with the intention of stimulating differentiation of the LSCs population and induce cancer cell death Our research further validates KAT2A as an effective and druggable target in cancer and by exploiting PROTAC capabilities, the degradative approach of KAT2A – a key player in maintaining the AML phenotype – presents a major opportunity for developing an orally available AML therapy.

Funding acknowledgement: Medical Research Council and Wellcome Trust

(1), Simon

Patient perspectives on the discontinuation of bevacizumab: results from a qualitative embedded study within VALTIVE1, an advanced ovarian cancer biomarker study.

Dr Daniella Holland-Hart (1), Dr Noreen Hopewell-Kelly (1), Anthony Byrne (1), Prof. Annmarie Nelson (1)

Marie Curie Research Centre, Cardiff University 1.

Background: VALTIVE1 is a biomarker study for patients with stage III and IV ovarian cancer. Plasma samples (Tie2 level) are collected during standard treatment comprising chemotherapy and bevacizumab which aims to prevent tumour growth. This qualitative study explored trial participant’s perceptions of how they might feel if bevacizumab was to be discontinued based upon the results from the biomarker test It aims to assess acceptability and feasibility of a potential VALTIVE2 study.

Methods: Qualitative semi-structured interviews were conducted with participants over the telephone from five sites across the UK. Interviews explored participants’ perceptions and experiences of the trial, treatments and Tie2 level biomarker test. Interviews were analysed using inductive and deductive thematic analysis.

Results: Qualitative interviews took place with 11 female participants. Most participants felt that it was acceptable, if not preferable to be allocated to a group where bevacizumab may be discontinued based upon the results from the biomarker test. A clear preference was stated to be informed of the biomarker test results. Common sideeffects attributed to bevacizumab included as stiffness, pain, fatigue, nosebleeds and muscle aches. The combination of chemotherapy and bevacizumab was felt to have influenced the severity of the side-effects

Conclusion: Participants indicated a preference to know whether bevacizumab was working and to discontinue bevacizumab if it had not prevented tumour growth based on the biomarker results. A future trial should consider ensuring all participants have access to test results It should also consider individual’s treatment tolerability in relation to poly-pharmacy and comorbidities.

Funding acknowledgement: Cancer Research UK

Validation of Tie2 as the first tumour vascular response biomarker for VEGF Inhibitors: VALTIVE1

Margherita Carucci (1), Magdalena Slusarczyk (1), Alys Irving (1), Dimitrios Profer (1), Cong Zhou (2), Philip Monaghan (3), Monica Narasimham (2), Sue Campbell (4), Hilary Morrison (4), Andrew Clamp (2,3), Richard Adams (1), Gordon Jayson (2,3)

1. University of Manchester

Centre for Trials Research, Cardiff University

2 The Christie NHS Foundation Trust

4.

3. Research Partner

Background: Tumours require a blood supply to provide them with oxygen and nutrients and to enable spread of cancer through blood vessels to other organs (metastasis). The formation of new blood vessels is known as angiogenesis, which is controlled by a growth factor called Vascular Endothelial Growth Factor (VEGF). Many drugs have been developed that block VEGF and, in most tumour types, including ovarian cancer, the addition of VEGF inhibitors (VEGFi) to conventional anti-cancer therapy postpones recurrence of the disease Yet, until now, there have not been any biomarkers that could be used to tell patients and their doctors whether the drugs are working or not.

The VALTIVE team has discovered the first biomarker that tells us whether a VEGFi is blocking a tumour’s blood supply. The test involves measuring a protein in the blood called Tie2 for defining the patient’s vascular response to the VEGFi.

Methods: VALTIVE1 is a multi-centre, single arm, non-intervention biomarker study to evaluate whether the Tie2 blood test can predict the response to VEGFi bevacizumab in 205 adult patients with Stage III-IV ovarian cancer receiving treatment with first line carboplatin and paclitaxel chemotherapy and bevacizumab, with or without olaparib. The Tie2 test will be performed on participants’ plasma samples collected before, during and after treatment. Primary endpoint is the definition of Progression Free Survival (PFS) difference between Tie2-defined vascular responders and Tie2-defined vascular non-responders.

The aim of VALTIVE1 is to evaluate the frequency and numbers of plasma samples for optimising the definition of Tie2-vascular response. These data will be used in a subsequent randomised study, VALTIVE2, in which patients receiving bevacizumab will be randomly allocated to the conventional 12 months of bevacizumab or Tie2-guided bevacizumab therapy.

Funding acknowledgement: CRUK

Understanding the variation of modern endoscopic ultrasound use in patients with oesophageal cancer (VALUE): a multi-methods study

K. Foley (1), J. Franklin (2), A. Cook (3), T. Underwood (4), K. Cozens (3), C. Boxall (3), K. Bradbury (5), M. Fay (6), D Chuter (6), B Lindfield (3), C Hurt (3)

1.

Division of Cancer & Genetics, Cardiff University

Institute of Medical Imaging, Bournemouth University

2. Southampton Clinical Trials Unit, University of Southampton

3

4. Psychology, University of Southampton

School of Cancer Sciences, Faculty of Medicine, University of Southampton

6.

5. Patient Representative & PPI Lead

Introduction: 9,000 UK patients are diagnosed with oesophageal cancer annually. Decision-making about treatment options is largely influenced by radiological staging, which may include computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) EUS use around the UK varies and since the introduction of PET-CT, the value of EUS has been questioned. VALUE aims to understand this variation and determine how often and why EUS changes decisions. VALUE will evaluate patient and clinician opinions and experiences about EUS.

Methods: 180 patients with potentially curable oesophageal cancer will participate. Patients will be recruited at eight UK sites, consented (if eligible) and registered onto iMedidata. Clinical and demographic data, staging, pre/post EUS treatment, and complications will be collected. We will attempt to sample ethnic minority patients from the data, as they are underrepresented in research Up to 30 patients and 30 clinicians will be interviewed to investigate the use of EUS and experiences of both patient and clinician.

The primary endpoint is the proportion that EUS changes MDT decisions. The observed proportion against a null hypothesis of 5% (considered too small to be of clinical use) will be tested using an hypothesis of 10% (considered beneficial). With 180 participants, there will be 85% power based on an one-sided test with 5% type I error rate. This study is funded by the NIHR (Reference:NIHR204931) and the views expressed in this abstract are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Funding acknowledgement: NIHR

24/T45

Early Phase Clinical Trial Patient Experience Questionnaire – Decision making and decision fatigue

Katie Gilmour (1), Gabby Brutto (1), Jenni Davies (2), Hannah Woodington (2)

Early Phase Research Nurse, Velindre University Health Board.

1. Haematology Research Nurse, Cardiff and Vale University Health Board 2.

Recent research has explored the ethical conflict of patients being educated sufficiently in decision making to participate in early phase clinical trials. Evidence suggests patients predominantly participate for therapeutic benefit and may lack understanding of early phase trial purposes to assess safety and tolerability of a particular drug. Early Phase (EP) Clinical trials are offered at a transitional point in a person’s illness trajectory and arguably individuals and families are at a point of decision fatigue.

A Patient experience questionnaire has been collaboratively developed between haematology and oncology research nurses at two different hospital trusts The questionnaire aimed to ascertain what is important to patients at this juncture in their health journey. The core values of acceptance, reconciliation, hope, autonomy, body preservation and altruism formed the basis of exploring patient experience. In addition, the questionnaire has a focus on the patient experience of decision making when commencing an early phase trial. How do patients experience decision fatigue when their illness trajectory offers them early phase clinical trial opportunities? Are they offered adequate support to make a decision that is right for them?

The questionnaire will be piloted with EP patients at two hospital sites to ascertain patient experience and provide information on adequacy of support in decision making It is hoped that this information will contribute to better patient care and improved practice, but also stimulate further investigation into supporting patient decision making at a critical juncture.

Research staff, who are we?

Julie Graham (1)

Velindre Cancer Centre 1

Our role in research is often misunderstood.

We are an integral part of the Multi-disciplinary Team, our role is to facilitate patient’s access to clinical trials and subsequent participation in a clinical trial as part of their treatment. This, unlike other nursing roles utilises the unknown of cutting edge medicine, either involving but not limited to new drugs, and or equipment. The role of the research nurse/officer has many facets, some of which are to ensure that patients are safe, and their best interests are always adhered to.

The Research Nurse and Research Officer needs in depth knowledge regarding research governance, such as Good Clinical Practice and undertake specialist training from research organisations like Health and Care Research Wales, various Clinical Trials Sponsors and specific training related to the vast amount of new treatments that are driving modern medicine forward.

Research Nurses have a clinical role, there is a requirement for research staff to collect data for studies This is governed by the Trial Sponsors, whether they are a pharmaceutical company or academic Institution. This variation of work adds to the enjoyment and complexity of the role.

One of the most rewarding parts of our role, is the ability to be able to care for our patients in a controlled setting with optimal nurse to patient ratios. Due to the exactness required for data collection, using our skills and knowledge, with a strong ethical element we ensure patients are the centre of our care.

Upskilling the workforce to deliver Advanced Therapy

Medicinal Products (ATMPs) to Cancer Patients across multiple sites – an Agile workforce.

Claire Lang (1), Katie Gilmour (1), Gabriella Brutto (1)

Clinical Research Unit, Velindre University NHS Trust 1

Advanced therapies are complex early phase clinical trials that are of increasing interest in all Cancers. These Gene, Cell and Tissue Engineered therapies should be available to all cancer patients equally across Southeast Wales and there is a partnership working collaboratively to develop a skilled and experienced workforce to deliver these complex ATMPs.

The partnership vision is to have a research team that delivers clinical trials of ATMPs to both oncology and haematology patients, currently these two cohorts of patients are managed by two separate health boards. The challenge is to develop one specialised workforce that would be able to deliver ATMPs competently and safely to both haematology and oncology patients at one health board.

Colleagues from both health boards were invited to attend scoping exercises across the UK to learn best practice and safe patient management in the delivery of ATMPs. It was found that many UK centres currently have joint haematology and oncology nursing teams. Specialist Nurse Educators at both health boards have worked collaboratively to review current training initiatives and have developed a training package to support a competent and agile workforce.

Networking across research teams and disease sites have created a foundation for collaboration, teamwork and resource and expertise sharing The ongoing aims are to streamline processes for delivering ATMPs for all cancers within one specialist research unit and offer parity of opportunity for the people of Southeast Wales.

24/T48

Successful screening for Clinical Trials, what does it look like?

Amanda Jackson (1), Michelle Harry (1)

Clinical Trials Unit, Velindre University NHS Trust 1.

In the ever changing health care landscape, patient recruitment to clinical trials has become at times challenging. There is a need to increase capacity, without increasing resource, and part of this, is revising how we successfully screen and recruit potential participants to clinical trials, especially those which require increased screening activity.

We are participating in a global study which essentially has three parts, pre-screening, screening and randomisation, the pre- screening requiring high level of resource. The expectation is that only 10% of people in the UK will be eligible for this particular study based on positive ctDNA in blood and tumour. Translating to the screening of 100 patients to find 1 eligible participant.

As the screening is so resource heavy, it has been important for us to devise a streamlined approach for prescreening to capture all possible eligible candidates.

Our strategy to deliver this has been a great success We are leading nationally on screening and are the first centre to randomise a patient nationally. The Sponsor has requested we share our strategy with them to guide other centres with the intention of enhancing recruitment nationally and globally.

This is of particular importance, as the sponsor is responsible for a portfolio of similar studies which they are hoping to roll out globally. Our screening strategy could potentially be adopted by all other sites as a sponsor directive, on the basis of our success.

Examining the pattern of Demographic Factors and Bone Marrow

Transplant requirement at Randomisation: Insights from the NCRI AML 18

Randomised Trial

Malavika Babu (1), Abin Thomas (1), Ian Thomas (1), Angela Casbard (1), Nigel H. Russel (2)

Centre for Trials Research, Cardiff University, Cardiff, United Kingdom.

2.

1. Guy’s and St Thomas’ National Health Service Foundation Trust, London, United Kingdom.

The AML 18 trial evaluates the effectiveness of different treatment options in older patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Patients entering the trial could be randomised more than once at different levels in their treatment. Subsequent treatment was then given, based on either the response to the prior treatment, or specific eligibility criteria or both. Use of multiple randomisations may introduce discrepancies in demographic factors such as gender, age, ethnicity, and transplant requirements, potentially influencing the overall results. We examined the pattern of demographic factors at each randomisation and their influence to alter the outcome comparisons, including progression to transplant.

This trial initially randomised a total of 1955 patients, primarily aged 60 and above, who were considered appropriate for an intensive treatment approach. After course 1, 916 (46.8%) patients were assigned randomly to the second course of treatment. Subsequently, 290 (31.7%) patients were randomised for the third course. Patients randomised in the first course had a median age of 68 (IQR =64, 71), which remained consistent with second and third randomisations. The proportion of males randomised remained consistently around 60% across all three randomisations. 95% of patients consistently identified as White across the randomisation

The patients who received a transplant at any time varied slightly across the three randomisations, with percentages of 69%, 62%, and 74% for the first, second, and third randomisations, respectively. We have observed similar patterns when we subgrouped the patients who received DA as their first line of therapy.

Nutritional care of people with colorectal cancer receiving non-surgical treatment

Hopkinson

1

School of Healthcare Sciences, Cardiff University, Wales, UK

2.

School of Biosciences, Cardiff University, Wales, UK

3.

School of Health Sciences, University of Southampton, England, UK

4.

5

School of Biomedical Sciences, Swansea University, Wales, UK

Institute of Applied Technology, Abu Dhabi Vocational Educational and Training Institute, United Arab Emirates

Purpose: To conduct a systematic review of literature about the oral intake and nutritional care of people receiving non-surgical treatment for colorectal cancer.

Background: Eating problems during cancer treatment are common. Undernourished patients experience more severe treatment toxicity, poorer treatment tolerance, and a more than doubled mortality rate compared to wellnourished patients. Dietary intervention is recommended for people receiving cancer treatment who are malnourished or at risk of malnutrition

Methods: A systematic search of MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, and reference lists of retrieved publications, identified empirical research in English language and date range 1/2011 to 8/2021. Two researchers independently screened records and extracted data prior to thematic analysis and interpretation informed by the Capability, Opportunity, Motivation, Behaviour (COM-B) model of behaviour change. The protocol was registered on PROSPERO.

Results: The search identified 3,101 records. The 29 publications included were: five about patient experience, 11 observational cohort studies, two about a special diet, three studies testing nutritional supplements, and eight studies testing multicomponent nutritional care (complex interventions). Cross-cutting themes were adherence, nutritional counselling, nutritional care, and outcomes of nutritional care

Analysis and Implications: Analysis identified a nutritional care process, interpreted through the lens of behavioural change theory to generate a new model of nutritional care for adherence. Patient education and feedback evoking positive emotion are proposed mechanisms important for motivating adherence These mechanisms should be tested for impact on the known problem of patient adherence to nutritional advice during cancer treatment.

Jane

(1), Tessa Watts (1), Nichola Gale (1), Adam Higgins (2), Samantha Sodergren (3), Anna Derrick (4), Abdiraheem Ali (5)

A rapid realist review: How do shared decision-making approaches, decision aids and communication tools influence the experience of making decisions about palliative treatments and supportive care for patients with advanced (non-curative) cancer?

Edwards

Marie Curie Research Centre, Cardiff University

1. Faculty of Life Sciences and Education, University of South Wales

2. Public Contributors 3.

Background: Patients with advanced non-curative cancer are typically offered active palliative treatments (chemotherapy and radiotherapy). Supportive care is an alternative option to these treatments and decisionmaking relating to treatment and care should include patients’ personal priorities and preferences. We aimed to identify contextual factors and mechanisms associated with communication and decision-making in clinical consultations when patient aids and shared decision-making approaches are used to support palliative treatment and care decisions, and to explain how they impact on patients’ experiences.

Methods: A realist review method was used to identify, appraise, synthesise and analyse research evidence by creating a list of theories explaining connections between contextual factors, intervention mechanisms and patient experience outcomes and synthesising the m with a middle-range theory of end-of-life decision-making to create a programme theory

Results: The evidence presented in 41 papers included in the review were integrated into a programme theory that explains how patients’ (and family) experiences and clinician support and communication can influence patient’s engagement with decision-making and satisfaction with decisions via mechanisms such as: enabling preparation for decision-making, accessible information, palliative care clinician involvement and patients’ reflection on their preferences and prior experiences of treatment decision-making.

Conclusion: To improve patients’ experiences of making decisions about palliative treatments and supportive care they need time to engage with key information and reflect on previous communication and decision-making. The programme theory developed from this review can help inform improvements in communication and treatment decision-making for patients with advanced and non-curative cancer.

Funding acknowledgement: Wales Cancer Research Centre

Michelle

(1), Daniella Holland-Hart (1), Mirella Longo (1), Clare Churcher (2), Kathy Seddon (3), Peter Buckle (3) Anthony Byrne (1), Annmarie Nelson (1)

24/T53

Patient and Public Involvement in a Pan European Palliative Care Study: the Serenity study PPI protocol

Michelle Edwards (1) , Annemarie Nelson (1) , Elin Baddeley (1), Kathy Seddon (1), Mark Pearson (2), Anette Arbjerg Højen (3), Suzanne Cannegieter (4), Isabelle.mahe (5), Johan Langendoen (6), Stavros Konstantinides (7), Sebastian Smit (8), Simon Moojart (9), Erik Klok (10), Simon Noble (1)

1.Marie Curie Research Centre, Division of Population Medicine, Cardiff University, UK 2.Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, UK 3. Aalborg University Hospital, Aalborg, Denmark 4. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands 5. Hôpital Louis Mourier, Service de Médecine Interne Université Paris Cité, France 6. Todaytomorrow, Netherlands 7.University Medical Center Mainz, Mainz, Germany 8. Department of Cardio-Oncology, Centre of Postgraduate Medical Education, Poland 9 Department of Medicine – Internal medicine and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands 10. Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands

Background: There are benefits and risks to health and quality of life for patients who are taking blood thinning medication towards the end of life. Serenity is a European research programme to develop and evaluate the clinical effectiveness of a digital shared decision-making support tool (SDMST) to support patients receiving palliative care for advanced cancer to participate in decisions about continuing or stopping blood thinning medication Multiple research methods are included in seven work-packages across eight countries Patient and Public Involvement (PPI) will be implemented in all work packages to optimise the quality of the research, ensure that research processes are likely to be acceptable to participants and that the SDMST will be appropriate for the study population.

Method: The Serenity PPI strategy is informed by reviews of international and European PPI in healthcare research, examination of the study protocol, a researcher survey (exploring researchers’ knowledge, experiences and expectations of PPI), consultations with work package leads (to create action plans). The progress and impact of PPI is being tracked using a Public Involvement in Research Impact Toolkit (based on UK standards).

Results: So far, PPI has been implemented in the first three work packages and has helped provide insights to a realist review findings, focus the conduct and content for patient interviews, and contribute to the interpretation of qualitative interview data and quantitative data.

Conclusions: We will report evidence of best practice based on the Serenity PPI strategy and produce guidance on future implementation of PPI in Pan-European research

Funding acknowledgement: Horizon Europe/Innovate UK

Information and

communication

needs of patients with advanced incurable cancer and their caregivers: A rapid review

Dr Daniella Holland-Hart (1), Dr Silvia Goss (1), Dr Isabel Hope (1), Mala Mann (1)

Marie Curie, Cardiff University 1.

Background and Aims: People with advanced incurable cancer and their caregivers face challenging issues related to their prognosis and end of life. However, relevant information is not always readily available or communicated appropriately. This review aims to collate research evidence on the key information and communication needs of people with advanced incurable cancer and their caregivers

Methods: This review used PaCERS methodology to identify relevant qualitative data focused on the perspective of patients and caregivers. MEDLINE, EMBASE, PsycINFO Cochrane and Scopus databases were searched for articles published after 2013 Studies were selected after review of the title and abstract Full texts were then assessed according to inclusion criteria. Data extraction and critical appraisal were completed. Thematic analysis was conducted.

Results: The search generated 1349 citations After abstract screening, 74 full texts were retrieved, with 20 texts subsequently removed. Another 16 texts were removed after data extraction and quality assessment, resulting in 38 final texts. Key themes included the need for personalised information in accordance with individual preferences, including when and how information is communicated. Adequate time, openness and sensitivity provided by healthcare professionals were important to facilitate understanding of prognosis, options for treatment and care. Avoidance of negative emotions and inadequate health literacy were barriers to understanding information, while early access to palliative care specialists and staged information were facilitators.

Conclusions: This review highlights key information and communication needs that can inform policy and practice. The barriers and facilitators identified should be considered when implementing communication strategies.

Funding acknowledgement: The authors are funded as follows: Daniella Holland-Hart: Wales Cancer Research Centre, Silvia Goss and Mala Mann: Marie Curie and Isabel Hope: Health Education and Improvement Wales.

Are QR code wristbands acceptable to cancer patients receiving palliative intent oncology treatment?

Elin Harding (1), Nikki Pease (1)

1.

Velindre Cancer Centre

Background: Palliative oncology patients frequently access unscheduled care. Such situations are more difficult for emergency healthcare professionals when information about a patient’s primary disease, comorbidities, treatment options and advance care plans (ACPs) are not readily available. In parts of England, local Electronic Palliative Coordination of Care systems (EPaCCS) allow sharing of this type of information across emergency, primary and secondary care, to ensure patient specific contemporaneous information is readily available. Currently in Wales no such electronic system is available, potentially resulting in less coordinated care, leading to avoidable hospital admissions particularly in the last year of their lives.

QR code wristbands linking to a patient specific profile containing pertinent information on diagnosis, treatment plans, medication and care preferences may result in better coordinated care by facilitating timely access to patient information; however, are such systems acceptable to palliative oncology patients?

Method: Thirty randomly selected patients receiving palliative intent oncology treatment attending an outpatient clinic, were shown the QR wristband system linked to a pre-populated test patient site. They were then supported in completing a survey developed on MS forms seeking their views on the QR code wristband system.

If found to be acceptable, further research is required to better understand what content and format of information emergency healthcare professionals such as paramedics require to impact their clinical decision making at scene Ultimately, implementation of a QR system has the potential to improve clinical decision making, reduce unnecessary hospital admissions, reduce patient and relative anxiety and potentially improve quality of life.

24/T61

Feasibility of a Targeted Intensive Community-based campaign To

Optimise vague Cancer (TICTOC) symptom awareness and help-seeking in an area of high socioeconomic deprivation

Pamela Smith (1), Gwenllian Moody (2), Eleanor Clarke (1), Julia Hiscock (3), Rebecca Cannings-John (2), Julia Townson (2), Adrian Edwards (1), Harriet QuinnScoggins (1,4), Bernadette Sewell (5), Daniel Jones (6), Christina Lloydwin (7), Sara Thomas (8), Dawn Casey (7), Catherine Lloyd-Bennett (9), Helen Stanton (2), Fiona Lugg-Widger (2), Dyfed Huws (10, 11), Angela Watkins (1,4), Gareth Newton (12), Ann Maria Thomas (12), Mike Robling (2), Grace McCutchan (1,13), Kate Brain (1)

1 Division of Population Medicine, Cardiff University 2 Centre for Trials Research, Cardiff University 3 North Wales Centre for Primary Care Research, Bangor University 4 PRIME Centre, Cardiff University 5 Swansea Centre for Health Economics, Swansea University 6 Leeds Institute of Health Sciences, University of Leeds 7 Cwm Taf Morgannwg University Health Board 8 Cwm Taf Morgannwg Public Health Team, Public Health Wales 9 Swansea Bay University Health Board 10 Welsh Cancer Intelligence and Surveillance Unit, Public Health Wales 11 Population Data Science, Swansea University Medical School 12 Patient and Public Involvement, Cardiff University 13 WCRC, Cardiff University

Background: Rapid Diagnostic Centres (RDCs) are being implemented to accelerate diagnosis of vague suspected cancer symptoms. We assessed the feasibility of a targeted community-based intervention to support the RDC pathway.

Design: Mixed-methods evaluation of the TIC-TOC intervention delivered during COVID-19 in deprived communities in Wales. Intervention messages were delivered by trained lay cancer champions and using broadcast, printed, outdoor and social media.

Methods: Data collection included (1) RDC patient questionnaires to assess the patient interval, (2) Facebook metrics and (3) qualitative interviews/focus groups with patients, members of the public, healthcare professionals and cancer champions. Feasibility was assessed as ‘green’ (deliverable), ‘amber’ (amend) or ‘red’ (review). Findings were discussed during a stakeholder workshop

Results: Of 243 RDC patients, 21% completed the questionnaire (amber) with <20% missing data (green). Seventy two percent of intervention participants were from the two most deprived quintiles (green). Patient interval measurement was sub-optimal.

Facebook advertisements reached 237,023 people and received 8,164 post engagements. Most intervention components were deliverable, except for bus adverts, newspaper stories, TV interviews and leaflets.

Qualitative findings with cancer champions highlighted the importance of confidence, teamwork, having a defined role and pre-existing community links. COVID-19 adaptations to RDC clinics were considered by staff to increase patient overwhelm, adversely impacting questionnaire recruitment. Stakeholders perceived value in taking this work forward and considered the cancer champion role to be central

Conclusions: TIC-TOC was mostly feasible to deliver and evaluate. Further implementation and evaluation require refinements to data collection methods and the trained cancer champion role.

The Yorkshire Enhanced Stop Smoking (YESS) study: process evaluation of a personalised intervention to support smoking cessation within lung cancer screening

Harriet Quinn-Scoggins (1,2), Pamela Smith (1), Grace McCutchan (1,3), Hoang Tong (1), Samantha Quaife (4), Mat Callister (5,6), Rebecca Thorley (7), Panos Alexandris (4), David Baldwin (8), Rebecca Beeken (6), John Britton (7), Harriet Copeland (6), Christos Chalitsios (7), Philip Crosbie (9), Sarah Lewis (7), Richard Neal (10), Steve Parrott (11), Rhian Gabe (4), Suzanne Rogerson (12), Qi Wu (11), Rachael Murray (7), Kate Brain (1,2,3)

1 Division of Population Medicine, School of Medicine, Cardiff University 2 PRIME Centre Wales, Division of Population Medicine, School of Medicine, Cardiff University 3 Wales Cancer Research Centre, School of Medicine, Cardiff University 4 Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London 5 Department of Respiratory Medicine, Leeds Teaching Hospitals NHS Trust Leeds Institute of Health Sciences, University of Leeds 6 Faculty of Medicine & Health Sciences, School of Medicine, University of Nottingham 7 Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust 8 Division of Infection, Immunity and Respiratory Medicine, University of Manchester 9 The University of Exeter Medical School, University of Exeter 10. Health Sciences, University of York 11. Department of Research and Innovation, 12. Leeds Teaching Hospitals NHS Trust

Rationale: Risk-stratified lung cancer screening with embedded smoking cessation has been recommended for implementation. The YESS study tested the effectiveness of an enhanced smoking cessation intervention (gold standard support involving behavioural support and pharmacotherapy + personalised booklet of images highlighting potential emphysema and/or coronary artery calcification) vs control (gold standard support only), delivered by trained smoking cessation practitioners (SCPs) This embedded process evaluation examined intervention setting, delivery, dose, and contextual factors.

Method: Qualitative interviews with 30 intervention and 15 control participants, and 30 participants who declined cessation support were analysed thematically Consultations with SCPs (10%) on the screening van and at intervention delivery four weeks later were audio-recorded and assessed for fidelity.

Findings: All participants described benefits of co-located and ongoing smoking cessation support. Immediate provision of pharmacotherapy and compassionate and holistic care was the main facilitator to initiating/sustaining a quit attempt Strong self-efficacy and response-efficacy beliefs regarding smoking cessation were expressed by intervention and control participants. Gold standard support was delivered with high fidelity (97.9%) on the screening van, and moderate fidelity (74.6%) at four weeks. The enhanced intervention was delivered with medium fidelity (76.9%) at four weeks.

Conclusions: Optimised gold standard support boosted receptivity for quitting irrespective of trial allocation. To harness the benefits of lung screening as a teachable moment for cessation to reduce smoking-related inequalities, we recommend co-located, high-intensity, person-centred smoking cessation support delivered by specialist SCPs. Offering this support could counteract contextual barriers to smoking cessation in lung screening candidates with long-term tobacco dependence.

Funding acknowledgement: Yorkshire Cancer Research

24/T63

Evaluating our evolving HCC service

Dr Tom Pembroke (1), Alison Prichard (1), Catrin Taylor (1)

HCC team, Gastroenterology, UHW, Cardiff 1.

The challenge of diagnosing and managing hepatocellular carcinoma (HCC) in South Wales is growing rapidly. Fatty liver disease is increasing, as is cirrhosis and portal hypertension, decompensation and liver cancer.

Historically: The local HCC service began in 2014; initially it was unfunded, based on clinical need, consisting of a 30-minute weekly meeting. There was limited radiology cover, and at its worst, there was a 9-week wait for MDT discussions. There was no clinical nurse specialist (CNS) support or key worker, and no dedicated out-patient clinic.

Aims: Our aims were to set up and deliver a seamless pathway for HCC patients, from point of suspicion to treatment, following the single cancer pathway (target of 62 days from suspicion to first definitive treatment). We strive for early diagnosis, streamlining and standardising services across the region, ultimately hoping to improve patient outcomes

Achievements: The HCC service now has a team which was established at the beginning of 2023: lead consultant (4 sessions), two regional hepatology consultants (1.5 sessions), diagnostic radiology (2 sessions), interventional radiology (1 5 sessions), medical oncology (1 5 sessions), clinical oncology (0 5 sessions), two full-time CNS, secretarial support and MDT co-ordinator. The weekly MDT has capacity to discuss 10 patients, most discussions happen within a week of referral.

In our weekly regional HCC clinic, patients can be reviewed by a consultant, usually with a CNS present, or by a CNS in the nurse-led clinic. Patient care is then coordinated by the CNS team, following the patient’s journey, using the new HCC database (close to 300 patients).

Feedback: (see poster for graph showing survey results)

Conclusion: Patient feedback shows high levels of satisfaction with the HCC service. The area of least satisfaction was having to travel to the central clinic but out-reach clinics are being established to help address this issue

24/T64

Optimising uptake of the Lung Health Check Operational Pilot within a socioeconomically deprived area of Wales

Chris Coslett (1), Claire Wright (1), Amy Smith (1), Grace McCutchan (2), Samantha Quaife (3), Kate Brain (4), Dafydd Snelling (5), Heather Ramessur-Marsden (5), Sinan Eccles (6)

Lung Health Check programme team, Wales Cancer Network

1 Wales Cancer Research Centre, Division of Population Medicine, Cardiff University

2.

3.

Wolfson Institute of Population Health, Queen Mary University of London

4.

Division of Population Medicine, Cardiff University

5 Cwm Taf Morgannwg University Health Board

Screening Engagement Team, Public Health Wales

6.

Introduction: The Lung Health Check (LHC) Operational Pilot (OP) for Wales will enable preparation for a national lung cancer screening programme roll-out Barriers to participation in LHCs include smoking-related stigma, fear and fatalism. We applied evidence-based best practice with the aim of optimising uptake.

Methods: The OP commenced in August 2023 in Cwm Taf Morgannwg University Health Board, serving a community with a high incidence of smoking and socioeconomic deprivation Strategies used to boost participation included:

(1) a low burden and targeted approach to invitation (pre-invitation information, pre-scheduled opt-out telephone appointments, streamlined telephone triage – “just a quick phone call”); (2) adapting existing invitation materials with input from patient groups to address psychosocial barriers to participation (e.g. non-judgement about smoking, incremental mention of lung cancer) and low literacy/numeracy (use of infographics, “Plain English” endorsement, “easy-read” versions), and (3) making the LHC appointment easily accessible (initial telephone-based triage, follow-up nurse appointment, CT scanner based at local community hospital).

Results: In total, 2130 individuals aged 60-74 years with a smoking history and resident in North Rhondda (South Wales) were invited, and 1241 (58.3%) completed a telephone triage. Of 859 individuals identified with a higher risk of lung cancer, 635 (73.9%) completed a telephone-based nurse appointment. The majority of those referred for low-dose CT screening (546/589, 92 7%) attended

Discussion: Uptake of the OP compares favourably to most other LHC activity previously reported. Strategies to encourage participation provide a promising template for wider roll-out across Wales.

How might the provision of smoking cessation services be adapted to improve uptake and success for people in low socioeconomic groups? A mixed-methods exploratory study (PROCESS Study)

Dr Pamela Smith, PhD (1), Lucia Dahlby, MScR (2), Dr Evgeniya Plotnikova, PhD (2), Rebecca Thorley (3), Dr RebeccaBell Williams, PhD (3), Dr Fiona Dobbie, PhD (2), Dr Tessa Langley, PhD (3), Dr Ilze Bogdanovica, PhD (3), Prof Kate Brain, PhD (1), Prof Rachael Murray, PhD (3), Dr Leah Jayes, PhD (4)

1 Usher Institute, University of Edinburgh

Division of Population Medicine, Cardiff University

2.

3.

Faculty of Medicine & Health Sciences, The University of Nottingham

4.

School of Social Sciences, Nottingham Trent University

Background: Smoking is a key driver of health inequalities and is an important factor in cancer incidence across the UK. Stop Smoking Services (SSS) offer a combination of behavioural and pharmacological support. Individuals who use SSS are three times more likely to successfully quit than those who try to quit unaided, but uptake of services is low, particularly amongst low socioeconomic groups.

Methods: A UK-wide mixed-methods study to understand the appeal, acceptability and accessibility of SSS for low socioeconomic groups, and the barriers and facilitators to uptake. The qualitative component involved interviews with SSS providers (n=22) and interviews with potential or current service users from low socioeconomic groups (n=115). Interviews were coded thematically using NVivo and analysed using the COM-B model which cites Capability (C), Opportunity (O), and Motivation (M) as three key factors for changing behaviour (B).

Results: Preliminary findings for Wales suggest that facilitators to accessing SSS include proximity of services, flexibility of mode of delivery, and free NRT provision. Barriers included waiting lists, staffing shortages, and lack of service visibility and advertisement. Recommendations included improved visibility and awareness of SSS (Capability), person-centred approaches to service delivery (Motivation) and community development initiatives (Opportunity).

Conclusion: Early findings from this study provide essential evidence on practical solutions for adapting SSS delivery, increasing equitable uptake and improving outcomes Results will be discussed at a roundtable with stakeholders from all four UK nations.

Funding acknowledgement: Cancer Research UK

24/T66

Early Detection and Diagnosis Marker Identification in Renal Cell Carcinoma: A Spatial

Transcriptomic Approach

Dr Andreia De Almeida (2), Diya Karwa (2), Dr Krishna Narahari1, (3), Professor Andrew Tee (1), John J. Bissler (4), Matthew Bareford (1,5)

1. Centre for Medical Education, Cardiff University

Division of Cancer and Genetics, Cardiff University

2. Urology, Cardiff and Vale University Health Board

3

4. WEQAS, Cardiff and Vale University Health Board

Division of Nephrology, St. Jude Children’s Research Hospital

5.

Background: Kidney cancer incidence has risen by over 30% over the last decade and projected to rise by a further 15% in the next, resulting in it being amongst the 5 most common cancer diagnoses in the UK. It remains one of only seven common cancers with increasing mortality rates with Survival rates in England and Wales amongst the worst in Europe.

The majority of kidney cancers do not cause readily identifiable symptoms; thus, are detected incidentally. This makes early diagnosis particularly challenging, with 1 in 5 kidney cancers incurable at time of diagnosis. Surgery remains the gold standard treatment but is less effective in cancers that have metastasized.

Aims:

- Spatial Transcriptomic characterisation of clear cell Renal Cell Carcinoma (ccRCC) tumour stages 1, 2 and 3.

- Identify differential expression in ccRCC tumour tissue and potential biomarkers for Early detection and diagnosis

Methods: Formalin fixed, paraffin embedded tissue sections of ccRCC Stages 1-3 and Birt-Hogg Dube kidney tumour sections were obtained from Wales Cancer Bank and collaborators Histopathological examination of H&E-stained Adjacent tissue sections by a pathologist and a Nephrologist to identify potential Regions of Interest (ROIs) was undertaken prior to samples undergoing the GeoMX Digital Spatial Profiling workflow, utilising CD45, PanCK, nuclear stain and Phospho-S6 Ribosomal Protein morphology markers along with Whole transcriptome atlas probes. Preidentified potential ROIs alongside morphology marker expression were then utilised to select and collect RNA from finalised ROI’s which were then sequenced.

Results: Results pending – Data analysis currently being undertaken.

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