postgraduate & early career researcher symposium …€¦ · our experienced panellists will...

ABSTRACT BOOKLET & PROGRAM

WEDNESDAY 26 JUNE 2019Chris O’Brien LifehouseLevel 5, Education Centre

POSTGRADUATE & EARLY CAREER RESEARCHER

SYMPOSIUM 2019

WELCOME MESSAGE DR MARISSA WILLIAMS & AMELIA SMIT

On behalf of the Organising Committee, it is our pleasure to welcome you to the 2019 Sydney Catalyst Postgraduate & Early Career Researcher (PG&ECR) Symposium. We are proud members of Sydney Catalyst and are excited to be the co-chairs for this year’s Symposium after participating in the 2018 Symposium Working Group.

The annual PG&ECR Symposium continues Sydney Catalyst’s commitment to promote collaboration and networking, bringing researchers together across the translational research spectrum. The event is a cornerstone of the Sydney Catalyst calendar.

We are thrilled and honoured to feature Professor Georgina Long, 2018 Cancer Researcher of the Year, as our keynote speaker. We will hear from Jay Allen, an inspiring and dedicated consumer advocate, who will share his experiences and his involvement in cancer research. Our experienced panellists will provide insight and helpful tips for navigating post PhD pathways and identifying career opportunities.

The Symposium features the diverse research of our network members that spans multiple disciplines including basic sciences, clinical and studies, psychosocial and implementation research. This year, to ensure a wider breadth of research is represented, we have included Rapid Fire sessions and a Virtual Symposium. The virtual platform hosts posters and presentations for you to peruse. Last year, the Virtual Symposium enabled new connections between researchers, and it’s a great opportunity to build your online academic profile.

We look forward to meeting you at this year’s Symposium and hope that the day will provide you with inspiration, cutting-edge knowlegde and new collaborators and contacts across the translational research spectrum.

WORKING GROUP

• Amelia Smit (Co-Chair) - The University of Sydney• Dr Marissa Williams (Co-Chair) - Asbestos Diseases Research Institute• Thomas Johnson - Asbestos Diseases Research Institute• Carolyn Mazariego - The University of Sydney• Dr Ashleigh Parkin - The Garvan Institute of Medical Research• Alison Young - The University of Sydney• Merilyn Heuschkel - Sydney Catalyst• Eve Simons - Sydney Catalyst• Cara McFarlane - Sydney Catalyst• Ellen Brodie - Sydney Catalyst


SYMPOSIUM 2019

Post PhD Pathways: Where to Next?Facilitated by Associate Professor Darren Saunders (University of New South Wales), with guest panellists:• Dr Cleola Anderiesz - Cancer Australia• Associate Professor Kellie Charles - University of Sydney• Dr Marina Kacevska - Bio-Rad Laboratories• Associate Professor Steven Kao - Chris O’Brien Lifehouse

Professor Georgina Long, BSc PhD MBBS FRACP, is Co-Director of the Melanoma Institute Australia (MIA), and Chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, The University of Sydney. She leads an extensive clinical trials team and laboratory at MIA, with a focus on targeted therapies and immuno-oncology in melanoma. She is principal investigator on phase I, II and III clinical trials in adjuvant and metastatic melanoma, including trials in patients with active brain metastases. She is the chief investigator on NHMRC funded research into the molecular biology of melanoma, with a particular interest in clinical and tissue biomarker correlates of systemic therapy sensitivity and resistance. In recognition of her ground breaking research, Professor Long has received a

number of awards, including the prestigious Sir Zelman Cowen Universities Fund Prize for Discovery in Medical Research in 2016, and a number of recent CINSW Premiers Awards for Outstanding Cancer Research. In 2018, she was awarded the Outstanding Cancer Researcher of the Year, 2014 she was awarded the Wildfire Award for the most highly-cited, original, peer-reviewed article published in 2011; and in 2013 she was named the Outstanding Cancer Research Fellow. She is the author of over 180 peer-reviewed publications in clinical and translational research in melanoma since 2011, including the New England Journal of Medicine, Lancet, Lancet Oncology, Journal of Clinical Oncology and Cancer Discovery.

Professor Long has presented her work at international conferences and meetings on more than 130 occasions. She is President of the prestigious international Society for Melanoma Research (President from 2018), is member (2015-2017) and Chair (2016) of the ASCO Scientific Committee for Melanoma/Skin cancer, is medical oncology lead for the Australian Melanoma Management Guidelines Committee, is on the editorial boards of several high-impact journals, and is a member of the Melanoma Expert Panel for AJCC Cancer Staging System 8th edition.

Professor Long was awarded the University Medal in Organic Chemistry. She subsequently completed her PhD in Chemistry in the field of anti-cancer agents and their binding to DNA. She then moved to the USA to take up a Fulbright Postdoctoral Fellowship at Scripps Research Institute, exploring nanotechnology in cancer treatment, before returning to Australia to complete her MBBS (Hons). Professor Long became a Fellow of the Australasian College of Physicians in January 2008, specialising in medical oncology.

KEYNOTE SPEAKER PROFESSOR GEORGINA LONG

PANEL DISCUSSION


SYMPOSIUM 2019


SYMPOSIUM 2019

CHAIRED BY CAROLYN MAZARIEGOPoCoG, The University of Sydney

PROGRAM

8.30 - 9.00am Registration - Tea, coffee and light refreshments provided

9.00 - 9.10am

9.10 - 9.20am

Introduction - Dr Marissa WilliamsChair, Postgraduate & Early Career Researcher Symposium Working GroupAsbestos Diseases Research Institute

Welcome - Professor Michael Boyer, Director of Sydney Catalyst

9.20 - 9.50am

Keynote Presentation - Professor Georgina LongCo-Medical Director of Melanoma Institute Australia (MIA)Chair of Melanoma Medical Oncology and Translational Research at MIARoyal North Shore Hospital, The University of Sydney

9.50 - 10.00am Question time

SESSION 1

10.00 - 10.45am ABSTRACT PRESENTATIONS (10mins + Questions)

10.00 - 10.15am

Brooke PereiraThe Garvan Institute of Medical ResearchTissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro

T1T2

10.15 - 10.30am

Joe JabbourChris O’Brien LifehouseDevelopment and assessment of an integrated patient information, education and support program in head and neck cancer – Comprehensive Head and Neck Cancer Education and Support (CHANCES) program

T2T3

10.30 - 10.45amChloe-Anne MartinezThe University of SydneyHIF-1 is activated in colorectal cancer in a cell culture model of obstructive sleep apnoea (OSA)

T1T2

10.45 - 11.10am RAPID FIRE PRESENTATIONS (3 mins)

Rapid Fire

Erin MothConcord General Repatriation General Hospital Older adults’ preferred and perceived roles in decision-making about palliative chemotherapy, their decision priorities, and information processes

T2T3

Rapid Fire

Andria May YaourtisThe University of SydneyThe development of a metal based complex with anti-metastatic activity in breast cancer cells in vitro

T1T2

Rapid Fire

Tong LiThe University of SydneyDifference of reading performance of Australian and Chinese radiologists in interpreting dense breast mammograms

T2T3


SYMPOSIUM 2019

Rapid Fire

Kendelle MurphyThe Garvan Institute of Medical ResearchPersonalised medicine approach in pancreatic cancer reveals fine-tuned stromal FAK manipulation improves global response the gemcitabine and abraxane while sensitising circulating tumour cells to shear stress in transit

T1T2

Rapid Fire

Ann LivingstoneNHMRC Clinical Trials Centre, The University of SydneyAre melanoma patients willing to accept the risks of adjuvant immunotherapy treatment to receive the benefits?

T2T3

Rapid Fire

Rebecca CuiRoyal Prince Alfred HospitalThe association between body mass index and liver resection outcomes in hepatocellular carcinoma and colorectal cancer metastases

T2T3

11.10 - 11.40am MORNING TEA

CHAIRED BY THOMAS JOHNSONAsbestos Diseases Research InstituteSESSION 2

11.40 - 12.40pm ABSTRACT PRESENTATIONS (10mins + Questions)

11.40 - 11.55am

Danielle GesslerSchool of Psychology, The University of Sydney Clinician-patient-family decision-making in adolescents and young adult cancer: A qualitative synthesis

T2T3

11.55 - 12.10pm

George JounThe University of SydneyBone morphogenetic protein signalling pathway acts at the roots of ovarian cancer chemo-resistance

T1T2

12.10 - 12.25pm

Rebecca VenchiaruttiSurgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred HospitalGeographic variation in time to diagnosis and treatment of oral cavity and oropharynx cancer in NSW

T2T3

12.25 - 12.40pm

Susannah HallalDiscipline of Pathology, Sydney Medical School, The University of SydneyEstablishing a SWATH-mass spectrometry biomarker discovery platform for comprehensive proteomics of plasma-derived extracellular vesicles for glioma tumour monitoring

T1T2

12.40 - 1.00pm RAPID FIRE PRESENTATIONS (3 mins)

Rapid FireTingting GongThe Garvan Institute of Medical ResearchAn interactive web app for evaluating somatic structural variant calling

T1T2

Rapid Fire

Clare TomsRoyal Prince Alfred HospitalFactors associated with length of stay in patients undergoing upper gastrointestinal cancer surgery

T2T3

Rapid FireJasmine YeeThe University of SydneyPhysical activity for women with metastatic breast cancer: a randomised feasibility trial

T2T3

Rapid FireLaveniya SatgunaseelanRoyal Prince Alfred HospitalRetrotransposon activity in young patients with oral squamous cell carcinoma (OSCC)

T1T2

Rapid FireLyndal AlchinRoyal Prince Alfred HospitalThe influence of stoma on quality of life before and after pelvic exenteration

T2T3

Rapid Fire

Nicci BartleyThe University of SydneyUncertainty experienced by adults undertaking cancer genome sequencing: Systematic review

T2T3

1.00 - 2.00pm NETWORKING LUNCH

CHAIRED BY ASHLEIGH PARKINThe Garvan Institute of Medical ResearchSESSION 3

2.00 - 2.45pm ABSTRACT PRESENTATIONS (10mins + Questions)

2.00 - 2.15pm

Lionel LeckThe University of SydneyOvercoming Pgp-mediated drug-resistance by releasing lysosomal stored doxorubicin with lysosomal targeting agents

T1T2

2.15 - 2.30pm

Rachael DoddThe University of SydneyPsychological impact of primary HPV testing: 12 months into the renewal of the Australian Cervical Screening Program

T2T3

2.30 - 2.45pm Jay AllenConsumer Presentation

2.45 - 3.10pm RAPID FIRE PRESENTATIONS (3 mins)

Rapid Fire

Yolande O’DonnellThe Garvan Institute of Medical ResearchSubcellular specific targeting of JNK as a novel anti-metastatic therapy in triple negative breast cancer

T1T2

Rapid Fire

Heidi MuellerRoyal Prince Alfred HospitalQuality of life in the initial 100 cases of cytoreductive surgery and heated intraperitoneal chemotherapy at the Royal Prince Alfred Hospital

T2T3

Rapid FireKenneth VuongRoyal Prince Alfred HospitalLong term pain and fatigue following pelvic exenteration

T2T3


SYMPOSIUM 2019

What did you think of the Sydney Catalyst Postgraduate & Early Career Researcher Symposium?Did you enjoy the day but have some suggestions for how we can improve for next time?

Log into our online program evaluation and tell is what you thought!

FEEDBACK

https://www.surveymonkey.com/r/PGECR2019

Rapid FireHolly HollidayThe Garvan Institute of Medical ResearchMicroRNA-based therapeutics for the treatment of high-risk neuroblastoma

T1T2

Rapid Fire

Mia MizukoshiFaculty of Health Sciences, The University of SydneyMammographic breast density of Japanese women living in Australia: Implication for breast screening policy

T2T3

Rapid Fire

Andrea SmithAustralian Institute of Health Innovation, Macquarie UniversityGPs and melanoma: How Australian GPs make sense of their role at the front line of melanoma care

T2T3

3.10 - 3.30pm AFTERNOON TEA

3.30 - 4.25pm

POST PHD PATHWAYS: WHERE TO NEXT?Panellists: • Dr Cleola Anderiesz - Cancer Australia• Associate Professor Kellie Charles - University of Sydney• Dr Marina Kacevska - Bio-Rad Laboratories• Associate Professor Steven Kao - Chris O’Brien Lifehouse

4.25 - 4.35pm AWARDS AND WRAP UP

4.35 - 5.30pm NETWORKING SESSION AND DRINKS

FACILITATED BY ASSOCIATE PROFESSOR DARREN SAUNDERSUniversity of New South WalesPANEL DISCUSSION


SYMPOSIUM 2019

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SYMPOSIUM 2019POSTGRADUATE & EARLY CAREER RESEARCHER

SYMPOSIUM 2019

RACHAEL DODD

The University of Sydney

Psychological impact of primary HPV testing: 12 months into the renewal of the Australian Cervical Screening Program

Dr Rachael Dodd is a Postdoctoral Research Fellow who has recently joined the School of Public Health. Rachael is a Research Psychologist who completed her Bachelors, Masters and PhD in the UK. Rachael’s PhD examined the psychosocial impact of of human papillomavirus oropharyngeal cancer. Rachael’s PhD studies covered a systematic review of the current literature examining the psychosocial impact of a HPV-OSCC diagnosis and knowledge of the relationship in patients, the public and health professionals; coverage of the relationship between HPV and oral cancer in the UK media; a qualitative study exploring the experiences of health professionals caring for HPV-OSCC patients; a survey of health professionals’ attitudes about discussing HPV; interviews with patients diagnosed with HPV-related oral cancer and their partners. Rachael’s final study involved the development of information materials to facilitate the discussion of HPV between health professionals and their patients.

REBECCA CUI

Royal Prince Alfred Hospital

The association between body mass index and liver resection outcomes in hepatocellular carcinoma and colorectal cancer metastases

NICCI BARTLEY


Uncertainty experienced by adults undertaking cancer genome sequencing: Systematic Review

Nicci Bartley is a PhD candidate at the University of Sydney, and Research Officer on the NHMRC funded project, Psychosocial issues in Genomic Oncology (PiGeOn Project). She holds a Bachelor of Psychology (Honours) and Master of Evaluation, and has over 10 years’ experience working in health behaviour research and program evaluation in Australia and Canada.

The PiGeOn Project aims to investigate the psychosocial, ethical and behavioural implications of cancer genome sequencing and Nicci’s PhD research focusses on how patients experience uncertainty when undertaking cancer genome sequencing, in both prevention and treatment contexts. She was awarded a Sydney Catalyst Postgraduate Research Scholarship in 2019 to support her PhD candidature.

LYNDAL ALCHIN


The influence of stoma on quality of life before and after pelvic exenteration

Lyndal Alchin is a Research Officer and Database Manager within the Surgical Outcomes Research Centre (SOuRCe) at Royal Prince Alfred Hospital. Lyndal’s work involves the management of a large clinical audit database as well as the long term quality of life follow up of patients who have undergone pelvic exenteration surgery. Lyndal’s background is in science and public health with an interest in women’s health. Lyndal was previously involved in the development of various clinical practice guidelines for different cancers, and is due to complete her postgraduate studies this year.

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SYMPOSIUM 2019

SUSANNAH HALLAL


Establishing a SWATH-mass spectrometry biomarker discovery platform for comprehensive proteomics of plasma-derived extracellular vesicles for glioma tumour monitoring

Susannah completed a Bachelor of Medical Science, majoring in biochemistry and immunology, from the University of Sydney. In 2014, Susannah was awarded Honours Class I and began her PhD in 2015, at the Brain and Mind Centre under the supervision of Dr Kimberley Kaufman and Associate Professor Michael Buckland. The focus of her PhD has been on understanding the role of extracellular vesicles (EVs) in glioblastoma progression. Susannah’s PhD has been supported by an APA scholarship and Australian Rotary Health top-up scholarship.

TINGTING GONG

The Garvan Institute of Medical Research

An interactive web app for evaluating somatic structural variant calling

Tingting is a second-year PhD student at the Central Medical School at the University of Sydney and Human Comparative and Prostate Cancer Genomics Laboratory at the Kinghorn Cancer Centre. The focus of her work is to use, evaluate and develop novel informatic and computational models to detect or infer complex structural variation (the hard-to-detect changes) within the human genome and more importantly unravel the type and nature of complex genomic rearrangements that drive human cancer, with a focus on prostate cancer.

DANIELLE GESSLER


Clinician-patient-family decision-making in adolescents and young adult cancer: a qualitative synthesis

Danielle is a provisionally registered psychologist who is passionate about translational clinical research in clinical psychology, medicine and public health. She has worked in psychiatry, neuroimaging and individual differences research, as well as in public hospital roles at Royal North Shore Hospital and Westmead Hospital. Her current research investigates health literacy and shared decision making in adolescents and young adults with cancer.

YOLANDE O’DONNELL


Subcellular specific targeting of JNK as a novel anti-metastatic therapy in triple negative breast cancer

Yolande O’Donnell has completed a Bachelor of Science (Honours) at the University of New South Wales, Sydney and continues her work as a Research Assistant under the supervision of Dr David Croucher in the Network Biology lab within the Cancer Division of the Garvan Institute of Medical Research. She has a particular focus on the pleiotropic role of c-Jun NH-Terminal Kinase (JNK) signalling in breast cancer, and has characterised the functional role of cytoplasmic JNK in triple negative breast cancer cell lines using a range of in vitro and in vivo techniques.

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SYMPOSIUM 2019

HOLLY HOLLIDAY


MicroRNA-based therapeutics for the treatment of high-risk neuroblastoma

Holly’s interests lie in the regulation of stem cells during development and disease. During her undergraduate studies, she undertook an Honours project investigating signalling pathways that control self-renewal and differentiation of naïve ES cells into primed early primitive ectoderm-like cells. Holly’s PhD project is focused on the regulation of mammary stem cells by helix-loop-helix transcription factors. In particular the transcription factor Inhibitor of Differentiation 4, which is essential for normal mammary gland development and has oncogenic functions in poorly-differentiated basal-like breast cancer. She uses a wide variety of techniques and sophisticated mouse models to define the role of helix-loop-helix transcription factors in mammary stem cells, uncovering a novel role for ID4 and E-proteins in the developing mammary gland. For her post doctoral studies Holly would like to transfer her skills into investigating transcriptional and epigenetic regulation of childhood cancers in order to better understand and treat these devastating diseases.

JOE JABBOUR

Chris O’Brien Lifehouse

Development and assessment of an integrated patient information, education and support program in head and neck cancer - Comprehensive Head and Neck Cancer Education and

Support (CHANCES) program

Dr Joe Jabbour is an aspiring Head and Neck Surgeon currently finishing a PhD through the University of Sydney. Dr. Jabbour graduated with a Bachelor of Medical Science with first class honours from the University of Sydney. His postgraduate medical training took place at the University of Notre Dame Sydney Medical School and he graduated with a Bachelor of Medicine/Bachelor of Surgery with First Class Honours. Dr Jabbour underwent junior medical officer training at Westmead Hospital in Sydney and was a general surgery SRMO position at St Vincent’s hospital. In 2018 he completed an unaccredited ENT surgery position at The Tweed Hospital.

GEORGE JOUN


Bone morphogenetic protein signalling pathway acts at the roots of ovarian cancer chemo-resistance

George is currently undertaking a PhD at Westmead Hospital, through the University of Sydney into ovarian cancer chemotherapy resistance. His ultimate goal in research is to deliver revolutionary drug targets down the translational pipeline for treatment of carcinoma. He hopes to pursue a career in academia or the pharmaceutical and biotechnology industries and would love to benefit from collaborations with industry and academic professionals. He hopes to see treatments for cancer improved due to the devastating burden it carries on individuals and family, communities and society. This will require investment and deep collaborations across academia, government, biotechnology and pharmaceutical industries if better cancer care is to be achieved in his lifetime.

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SYMPOSIUM 2019

TONG LI


Difference of reading performance of Australian and Chinese radiologists in interpreting dense breast mammograms

Dr Tong Li started her career in Health Sciences in 2008 with a Bachelor of Health Sciences and Master of Health Information Management from Latrobe University. She then moved into Medical Radiation Sciences and started her PhD in 2014. Tong is currently a Post-doc working for BreastScreen Reader Assessment Strategy (BREAST) at the Faculty of Health Sciences (FHS), the University of Sydney. Her research areas include epidemiology of breast cancer, optimisation of breast cancer early detection and breast screening, mammographic density and Digital Breast Tomosynthesis. She has published peer-review articles in the Journal of Oncology, Breast Cancer Research and Treatment, European Journal of Radiology and The Breast Journal. Her recent work has been presented at the 34th Annual Miami Breast Cancer Conference (USA), 5th World Congress on Breast Cancer (UK), Asian Pacific Organisation for Cancer Prevention APOCP 8th General Assembly (Australia), Sydney Cancer Conference and China-Australia Symposium on Breast Cancer Research.

Tong is a member of Executive Group of Cancer Diagnosis and Rehabilitation Theme at FHS and a member of the Medical Imaging Optimisation and Perception Research Group (MIOPeG), Sydney Catalyst, Cancer Research Network and China Studies Centre. She is developing international collaborations for BREAST, particularly in China. She also won the 2017 University of Sydney Three Minutes Thesis (3MT) Competition and the 2017 Faculty of Health Sciences Student Leadership Award.

LIONEL LECK


Overcoming Pgp-mediated drug-resistance by releasing lysosomal stored doxorubicin with lysosomal targeting agents

Lionel Leck is a first year PhD candidate in Medicine at the Department of Pathology, University of Sydney. His main research interest is on cancer multidrug resistance, specifically in the family of ATP-binding cassette (ABC) proteins of substrate transporters such as P-glycoprotein (Pgp) and multidrug resistance protein 1 (MRP1).

GEORGE JOUN


Bone morphogenetic protein signalling pathway acts at the roots of ovarian cancer chemo-resistance

George is currently undertaking a PhD at Westmead Hospital, through the University of Sydney into ovarian cancer chemotherapy resistance. His ultimate goal in research is to deliver revolutionary drug targets down the translational pipeline for treatment of carcinoma. He hopes to pursue a career in academia or the pharmaceutical and biotechnology industries and would love to benefit from collaborations with industry and academic professionals. He hopes to see treatments for cancer improved due to the devastating burden it carries on individuals and family, communities and society. This will require investment and deep collaborations across academia, government, biotechnology and pharmaceutical industries if better cancer care is to be achieved in his lifetime.

ANN LIVINGSTONE

NHMRC Clinical Trials Centre, The University of Sydney

Are melanoma patients willing to accept the risks of adjuvant immunotherapy treatment to receive the benefits?

Ann is currently a PhD student at the NHMRC Clinical Trials Centre (CTC), the University of Sydney. Her research focuses on adjuvant immunotherapy in melanoma. She has over 30 years of clinical healthcare experience and 15 years of clinical trials experience including melanoma, lung cancer and brain tumour trials development and operations. Her interests include health e conomics having completed a Graduate Diploma in Health Economics in 2016.

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SYMPOSIUM 2019

ERIN MOTH

Concord Repatriation General Hospital

Older adults’ preferred and perceived roles in decision-making about palliative chemotherapy, their decision priorities, and information preferences

Erin Moth is a Medical Oncologist with an interest in improving treatment decision-making and supportive care for older adults with cancer, which is the focus of her current PhD studies. She is currently working at Concord Repatriation General Hospital, completing her PhD studies through Concord Cancer Centre.

MIA MIZUKOSHI


Mammographic breast density of Japanese women living in Australia: Implications for breast screeening policy

Mia Mizukoshi is a Masters student in the Discipline of Behavioural and Social Sciences at the University of Sydney, Faculty of Health Sciences. Her research is in the area of breast density, breast screening and policy implications. She is currently working as a mammography specialised radiographer at BreastScreen, Sydney Local Health District. She is also a qualified radiographer in Japan and has experience in preventive healthcare, different health systems and patients with diverse ethnic backgrounds, she developed an interest in the areas of cancer screening policies and ethnic diversity including CALD communities.

CHLOE-ANNE MARTINEZ


HIF-1 is activated in colorectal cancer in a cell culture model of obstructive sleep apnoea

Chloe-Anne recently graduated with a Bachelor of Medical Science (Honours) at the University of Sydney. She completed her honours year under the supervision of Dr Kristina Cook and Professor Peter Cistulli and was awarded the University of Sydney Academic Merit Prize in 2018.

She was fortunate enough to be awarded with the A.E. and F.A.Q. Stephens Scholarship for her record of academic excellence and research potential, which will help to support her PhD candidature. She is currently a first year PhD student continuing her research with Dr Kristina Cook and Professor Peter Cistulli with the Sleep Research Theme at Charles Perkins Centre in the Faculty of Medicine and Health. Her project aims to investigate the molecular mechanisms underlying tumour development and progression in patients with obstructive sleep apnoea using in vitro cell culture models. Her work primarily focuses on the role of intermittent hypoxia and its effect on oxygen-sensitive molecules such as HIF-1.

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SYMPOSIUM 2019

HEIDI MUELLER


Quality of life in the initial 100 cases of cytoreductive surgery and heated intraperitoneal chemotherapy at the Royal Prince Alfred Hospital

Heidi joined SOuRCe in February 2018 as a Research Officer/ Data Manager for the Peritonectomy Surgical Research Program. Heidi completed a Bachelor of Science (Exercise Physiology) with a double minor (Nutrition and Physical Education) with Honours at the University of California in 2009. She went on to complete a Master of International Public Health in 2013 at the University of Sydney, including an Honours research praxis at the Cancer Council NSW working on the CLEAR study linking diet adaptations to colorectal cancer in migrants. She then went on to complete a Graduate Certificate in International Relations in 2015 from the University of Sydney with a six month research placement at the World Health Organization (WHO) in Fiji, where she worked on multiple research projects as well as ran her own follow up study on the double burden of malnutrition in the Pacific.

At SOuRCe, Heidi is working on the Peritonectomy Surgical Research Program (PREMIER), a comprehensive database capturing clinical, quality of life and patient reported outcomes measures following cytoreductive surgery & HIPEC.

KENDELLE MURPHY


Personalised medicine approach in pancreatic cancer reveals fine-tuned stromal FAK manipulation improves global response the gemcitabine and Abraxane while sensitising circulating tumour cells to shear stress in transit

Kendelle Murphy is a PhD student in pancreatic cancer research at the Garvan. She’s investigating how to improve patient sensitivity to the treatments that are commonly used to treat the disease, and improve outcomes.

BROOKE PEREIRA


Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro

Dr Brooke Pereira completed her PhD at the Biomedicine Discovery Institute (BDI) at Monash University, under the supervision of Professor Gail Risbridger, in late 2018. During her candidature she studied tumour-stromal interactions in prostate cancer using both tissue engineering and quantitative proteomic techniques. Brooke is now a post-doctoral research officer at the Garvan Institute of Medical Research, where she is investigating novel stromal targets in pancreatic cancer under the supervision of Associate Professor Paul Timpson. She is using a range of cutting-edge approaches such as patient-derived xenografting, intravital microscopy and MALDI imaging mass spectrometry to study the stroma of both murine and human pancreatic tumours.

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SYMPOSIUM 2019

ANDREA SMITH

Australian Institute of Health Innovation, Macquarie University

GPs and melanoma: How Australian GPs make sense of their role at their role at the front line of melanoma care

Andrea is a Research Fellow at the Australian Institute of Health Innovation (AIHI), Faculty of Medicine and Health Sciences at Macquarie University. She works within AIHI’s Centre for Healthcare Resilience and Implementation Science (CHRIS), where the focus is on investigating the myriad, dynamic interactions between interconnected webs of clinical professionals, their patients, healthcare technologies, communication systems and equipment.

LAVENIYA SATGUNASEELAN


Retrotransposon activity in young patients with oral squamous cell carcinoma

Laveniya divides her time between working as an anatomical pathologist at the Department of Tissue Pathology and Diagnostic Oncology at Royal Prince Alfred Hospital, and her PhD at the University of Sydney. Her PhD project aims to uncover the molecular mechanisms by which young people are developing oral cancers at an increasing rate, which integrates with her clinical work where her subspecialty interest is head and neck pathology. She is also a football tragic, supporting both Liverpool and the Western Sydney Wanderers.

CLARE TOMS


Factors associated with length of stay in patients undergoing upper gastrointestinal cancer surgery

Clare Toms is a Master of Philosophy candidate at the University of Sydney, investigating the quality of life in pancreatic cancer patients.

Clare works at the Surgical Outcomes Research Centre (SOuRCe) at Royal Prince Alfred Hospital as a Research Officer/ Data Manager for the Upper Gastrointestinal and Hepatobiliary Surgical Department. She is responsible for the management of the department’s clinical database to determine the efficacy and surgical outcomes for the Morbidity & Mortality audit and other research areas, of interest to the surgical team. Clare’s background is in anatomic science and public health. Her area of research interests include, pancreatic cancer management, quality of life in patients with UGI malignancy and surgical outcomes for UGI cancer patients.

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SYMPOSIUM 2019

KENNETH VUONG


Long term pain and fatigue following pelvic exenteration

Kenneth Vuong is a Research Officer and Database Manager at the Surgical Outcomes Research Centre at Royal Prince Alfred Hospital. His work involves running a range of research projects and the management of databases for the pelvic exenteration program. Kenneth’s background and interests lie in exercise science, dietetics and public health having completed a Bachelor of Applied Science (Exercise Sport Science) and a Bachelor of Science (Nutrition) with Honours in 2013 and a Master of Public Health (Professional Practice) in 2015 at the University of Sydney where he completed projects for the Office of Preventive Health.

ANDRIA MAY YAOURTIS


The development of a metal based complex with anti-metastatic activity in breast cancer cells in vitro

JASMINE YEE


Physical activity for women with metastatic breast cancer: a randomised feasibility trial

REBECCA VENCHIARUTTI


Geographic variation in time to diagnosis and treatment of oral cavity and oropharynx cancer in NSW

Rebecca is a second-year PhD candidate at the Sydney School of Public Health at the University of Sydney. Her work focuses on understanding geographic variation in pathways to diagnosis and treatment of patients with head and neck cancer in NSW. Rebecca is also a research officer at the Surgical Outcomes Research Centre at RPA Hospital. Rebecca’s research interests include cancer epidemiology, health services research, health disparities, and surgical outcomes research.

ABSTRACTSNAME TITLE T1/2/3 PAGE

Lyndal Alchin The influence of stoma on quality of life before and after pelvic exenteration T2-T3 18

Nicci Bartley Uncertainty experienced by adults undertaking cancer genome sequencing: Systematic review T2-T3 18

Rebecca Cui The association between body mass index and liver resection outcomes in hepatocellular carcinoma and colorectal cancer metastases T2-T3 19

Rachael Dodd Psychological impact of primary HPV testing: 12 months into the renewal of the Australian Cervical Screening Program T2-T3 20

Danielle Gessler Clinician-patient-family decision-making in adolescents and young adult cancer: A qualitative synthesis T2-T3 20

Tingting Gong An interactive web app for evaluating somatic structural variant calling T2-T3 21

Susannah HallalEstablishing a SWATH-mass spectrometry biomarker discovery platform for comprehensive proteomics of plasma-derived extracellular vesicles for glioma tumour monitoring

T1-T2 22

Holly Holliday MicroRNA-based therapeutics for the treatment of high-risk neuroblastoma T1-T2 23

Joe JabbourDevelopment and assessment of an integrated patient information, education and support program in head and neck cancer – Comprehensive Head and Neck Cancer Education and Support (CHANCES) program

T2-T3 23

George Joun Bone morphogenetic protein signalling pathway acts at the roots of ovarian cancer chemo-resistance T1-T2 24

Lionel Leck Overcoming Pgp-mediated drug-resistance by releasing lysosomal stored doxorubicin with lysosomal targeting agents T1-T2 25

Tong Li Difference of reading performance of Australian and Chinese radiologists in interpreting dense breast mammograms T2-T3 25

Ann Livingstone Are melanoma patients willing to accept the risks of adjuvant immunotherapy treatment to receive the benefits? T2-T3 26

Chloe-Anne Martinez HIF-1 is activated in colorectal cancer in a cell culture model of obstructive sleep apnoea (OSA) T1-T2 27

Mia Mizukoshi Mammographic breast density of Japanese women living in Australia: Implication for breast screening policy T2-T3 27

Erin Moth Older adults’ preferred and perceived roles in decision-making about palliative chemotherapy, their decision priorities, and information preferences T2-T3 28

Heidi Mueller Quality of life in the initial 100 cases of cytoreductive surgery and heated intraperitoneal chemotherapy at the Royal Prince Alfred Hospital T2-T3 29

Kendelle MurphyPersonalised medicine approach in pancreatic cancer reveals fine-tuned stromal FAK manipulation improves global response the gemcitabine and Abraxane while sensitising circulating tumour cells to shear stress in transit

T1-T2 30

Yolande O’Donnell Subcellular specific targeting of JNK as a novel anti-metastatic therapy in triple negative breast cancer T1-T2 30

Brooke PereiraTissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro

T1-T2 31


SYMPOSIUM 2019

Laveniya Satgunaseelan Retrotransposon activity in young patients with oral squamous cell carcinoma T1-T2 32

Andrea Smith GPs and melanoma: how Australian GPs make sense of their role at their role at the front line of melanoma care T2-T3 33

Clare Toms Factors associated with length of stay in patients undergoing upper gastrointestinal cancer surgery T2-T3 34

Rebecca Venchiarutti Geographic variation in time to diagnosis and treatment of oral cavity and oro-pharynx cancer in NSW T2-T3 34

Kenneth Vuong Long term pain and fatigue following pelvic exenteration T2-T3 35

Andria May Yaourtis The development of a metal based complex with anti-metastatic activity in breast cancer cells in vitro T1-T2 36

Jasmine Yee Physical activity for women with metastatic breast cancer: a randomised feasibility trial T2-T3 36

T

VIRTUAL POSTERS

Cecilia Chambers Inhibition of NPY signalling axis as a novel therapeutic option in pancreatic cancer T1T2

Bekesho Geleta A novel therapeutic approach to inhibit the oncogenetic cross-talk between pancreatic cancer cells and the surrounding stroma T1T2

Danielle Gessler Clinician-patient-family decision-making in adolescents and young adult cancer: A qualitative analysis T2T3

Jeremy Han Subcellular specific targeting of JNK as a novel anti-metastatic therapy in triple negative breast cancer T1T2

Thomas Johnson YB-1: an important driver of mesothelioma drug resistance and a potential novel therapeutic target T1T2

Hansol Lee Advanced melanoma patients with high CD16+ macrophages have better response and survival to anti-PD-1 based immunotherapy T1T2

Ashleigh Parkin Dual inhibition of JAK and Src: A novel and promising therapeutic combination for pancreatic cancer T1T2

Tahlia Scheinberg Evaluation of a mainstream model of genetic testing for men with prostate cancer - study schema All

Amelia Smit Delivering personal genomic risk of melanoma information to the public: social implications T2T3

Christina Stanislaus Overview of robotic cancer surgery in a tertiary public hospital T2T3

Marissa Williams Multiple mechanisms contribute to downregulation of tumour suppressor mircoRNAs in malignant pleural mesothelioma T1T2


SYMPOSIUM 2019

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SYMPOSIUM 2019The influence of stoma on quality of life before and after pelvic exenterationLyndal Alchin1, Cherry Koh1,2,3,4, Michael Solomon1,2,3,4, Kenneth Vuong1, Colleen Mendes3, Jane Young1,2,3,4, Daniel Steffens1,4

1 Surgical Outcomes Research Centre (SOuRCe), The University of Sydney & Sydney Local Health District 2 The Institute of Academic Surgery at Royal Prince Alfred Hospital, Sydney Local Health District 3 Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney Local Health District 4 Faculty of Medicine and Health, The University of Sydney

Pelvic Exenteration (PE) is often the only curative treatment for patients with advanced primary or recurrent cancers within the pelvis, involving complete or partial resection of many pelvic structures. While surgeons perform wider resection to achieve a clear surgical margin, the formation of at least one stoma post-operatively is almost inevitable.

To investigate the influence of stoma on quality of life (QoL) outcomes following PE surgery.

This was a cohort study of consecutive patients scheduled to undergo PE at Royal Prince Alfred Hospital, Sydney for advanced primary or recurrent cancers of the pelvis between July 2008 and December 2017. The primary outcome was QoL assessed with SF-36 Mental Component score (MCS) and Physical Component Scores (PCS) at baseline, 6, 12 and 18 months. Higher scores indicate better QoL. QoL trajectories were compared based on pre-operative stoma status (stoma versus no stoma) and post-operative number of stomas (1 stoma versus 2 stomas). T tests statistics were used for comparison of QoL outcomes within groups.

Of the 643 patients that underwent PE between 2008 and 2017, 297 were eligible and consented to the study. Most patients were male (62%) and underwent PE due recurrent rectal cancer (42%), presenting a mean age of 59 years. For those patients who had no stoma at baseline, PCS decreased from baseline to 6 months, returning to baseline scores by 12month and remaining stable thereafter. Conversely, PCS did not change during the study period for patients who had a stoma at baseline. MCS increased slightly throughout the study period for patients with or without stoma at baseline. No difference was found in PCS and MCS trajectories for patients who had one or two stomas after PE surgery.

The results of this study demonstrate that the presence of stoma, whether pre- or post-operatively, may not influence post-operative QoL outcomes in patients who have undergone PE.

Uncertainty experienced by adults undertaking cancer genome sequencing: Systematic reviewNicci Bartley1, Phyllis Butow1, Christine Napier2, Megan Best1 1 University of Sydney, Faculty of Science, School of Psychology, Psycho-Oncology Co-operative Research Group 2 Cancer Division, Garvan Institute of Medical Research

While genome sequencing (GS) provides new opportunities in clinical practice, the complexity of these technologies generate uncertainties. Little is known about the types of uncertainty, predictors of uncertainty, and the impact of uncertainty for adult patients undergoing cancer GS.

The aim of this systematic review was to determine what is currently known about the patient experience of uncertainty when undergoing cancer GS.

A comprehensive search of 5 databases between 2001 and 2018, for original research reporting patient uncertainty in the context of cancer GS was conducted, yielding 6,247 records. After removing duplicates 4,892 records were screened by title and abstract, 107 full articles were assessed for eligibility, and ten studies were included for data extraction and quality appraisal. Qualitative studies were subjected to thematic analysis, while quantitative data were summarised using descriptive statistics. Both datasets were then merged for the final synthesis. The ten studies comprised 1,897 patients. The majority of patients were female, with a personal or family history of breast, ovarian or colorectal cancer.

Multiple interrelated uncertainties can exist for patients undergoing cancer GS. Uncertainty can be a motivation for, or barrier to, pursuing cancer GS depending on the patients’ attitude towards uncertainty. Factors affecting uncertainty include misconceptions and inadequate information, poor health/genomic literacy, and health professionals’ approach

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SYMPOSIUM 2019to discussing uncertainty. The quantitative synthesis showed no difference in levels of uncertainty between patients who received positive, negative, or uncertain GS results; however, the qualitative synthesis found that patients who received uncertain GS results subsequently reported feeling more uncertain. In the few studies investigating the impact of uncertainty, patients reported feeling disappointed and frustrated by uncertainty, and were hesitant to share their uncertain GS results with relatives. The qualitative synthesis showed that coping strategies used by patients experiencing uncertainty included: information seeking, adopting risk management strategies, seeking support, and remaining optimistic or hopeful about future outcomes.

This systematic review highlights the need for more mixed methods longitudinal research to understand the experience of patient uncertainty across the GS process (e.g. waiting for and receiving results, making treatment/risk management decisions), as well as the long term psychosocial impacts of uncertainty for patients. The current evidence base described here can assist health professionals to identify and address patient uncertainty in this context.

The association between body mass index and liver resection outcomes in hepatocellular carcinoma and colorectal cancer metastasesRebecca B Cui, Jin-soo Park, Clare Toms, Cherry Koh, David Yeo Royal Prince Alfred Hospital

Obesity is a rising public health concern in Australia, which poses significant difficulties to surgeons associated with increasing technical challenges, and the physiological sequelae associated with metabolic syndrome leading to increased post-operative complications.

Our aims are to determine the prevalence of overweight/obese patients undergoing liver resection for hepatocellular carcinoma (HCC) and colorectal cancer metastases (CRCM), and the association between increased body mass index (BMI) and post-operative out

A retrospective study of patients undergoing liver resection for HCC/CRCM at a tertiary centre in Australia was performed over a four-year period (2013-2017). Data was collected of patient demographics, BMI, clinico-pathological characteristics of surgery, and co-morbidities. The primary outcome was incidence of complications. Secondary outcomes included 30-day readmission, return to theatre, mortality, and length of hospital stay.

180 patients underwent liver resection for HCC/CRCM over the study period (135M [75%], mean age 61.1 [SD11.2]). The mean BMI of the patients was 26.0 (SD4.9), with 89 patients (49.4%) being overweight (BMI>25), of which included 36 (20%) obese patients (BMI>30). Of these, male patients (n=72) tended to be overweight when compared to females (n=17) (p=0.05), and those undergoing surgery for CRCM (n=50) were more likely to be overweight than those undergoing resections for HCC (n=39) (p=0.01). There was no significant difference between the prevalence of COPD, DM or IHD in the overweight and obese group compared with normal weight group Of the overweight patients, 46 (25.6%) experienced complications, compared to 43 (23.9%) in the non-overweight group. Septic complications were significantly increased in overweight patients (OR2.35, 95%CI 1.03-5.35). Whilst post-operative liver dysfunction was not associated with increased BMI, it was increased in patients undergoing major liver resections when compared to minor resections (OR6.59, 95%CI 1.33-32.71). Length of hospital admission (LOS) was not increased in the overweight/obese group compared with those of normal BMI.

In our centre, half the patients undergoing liver resection for HCC/CRCM are overweight or obese. An increased BMI was found to contribute to higher incidence of post-operative septic complications, however few patients required take back to theatre or readmission, LOS was not increased.

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SYMPOSIUM 2019Psychological impact of primary HPV testing: 12 months into the renewal of the Australian Cervical Screening ProgramRachael Helen Dodd, Olivia Mac, Julia Brotherton, Kirsten Jo McCaffery Wiser Healthcare, Faculty of Medicine and Health, School of Public Health, The University of Sydney

Women have shown significant concerns about the recent changes to the Australian cervical screening program. One of the main changes to the cervical screening program was the change from a two-yearly Pap test to a five-yearly human papillomavirus (HPV) test. Previous research has shown women to overlook the change in the screening test, which is the basis for many of the changes made to the program. Due to the change in screening test, women now receive different results from the previous program.

To examine after 12 months, the psychosocial impact of HPV test results in a sample of women residing in Australia who have undergone screening under the renewed cervical screening program.

Participants were women residing in Australia aged 25 – 74 years who received cervical screening since December 2017 under the new guidelines. Participants were recruited through a market research company panel, Dynata, and completed an online survey. Primary outcome measures were anxiety and general distress. Qualitative interviews were conducted with a sample of these women with different test results (HPV+, HPV-, don’t know).

1004 women completed the online survey. The majority of women tested negative for HPV (81%), with 6% testing positive for HPV and 13% did not know or remember their test result. Women who tested positive for HPV were significantly more anxious (53.03 vs 43.58, p<0.001), distressed (3.94 vs 2.52, p=0.004) and concerned about their test result (8.6 vs 4.88, p<0.001) than women who tested negative for HPV. Women who tested positive for HPV expressed greater distress about their test result (7.62 vs 7.05, p<0.001) and cancer worry (2.28 vs 1.73, P<0.001) than women testing HPV negative. Women who tested positive for HPV also had greater knowledge of HPV (10.54 vs 7.95, p<0.001) and HPV testing (2.94 vs 2.09, p<0.001). Qualitative findings showed some women understood the HPV test is earlier detection and that HPV is common. A number of women said they had not been told about the changes when they went for cervical screening and not all women found out their results. A greater understanding of the changes was shown in women who tested HPV positive. A degree of trust in the changes was demonstrated by expressing trust in the reasons behind the changes and in their doctor.

Receiving an HPV positive test result as part of the revised cervical screening program has shown to significantly raise anxiety, general distress, concern about test results and distress about test results in women. These findings suggest the need to develop ways to mitigate this impact in women receiving HPV-positive test results.

Clinician-patient-family decision-making in adolescents and young adult cancer: a qualitative synthesisDanielle Gessler1,2, Ilona Juraskova1,2,6, Ursula Sansom-Daly3,4,5, Heather L Shepherd1,2,6, Pandora Patterson7,8, Danielle Muscat9 1 School of Psychology, The University of Sydney 2 Centre for Medical Psychology and Evidence-based Decision-making (CeMPED), The University of Sydney 3 Behavioural Sciences Unit, Kids Cancer Centre, Sydney Children’s Hospital 4 Discipline of Paediatrics, School of Women’s and Children’s Health, The University of New South Wales 5 Sydney Youth Cancer Service, Prince of Wales/Sydney Children’s Hospital 6 Psycho-Oncology Cooperative Research Group (PoCoG), School of Psychology, The University of Sydney 7 Cancer Nursing Research Unit, The University of Sydney 8 CanTeen Australia, NSW, Australia 9 Sydney Health Literacy Lab, School of Public Health, Faculty of Medicine and Health, The University of Sydney

Adolescents and young adults (AYAs) with cancer represent a minority group in the healthcare system. The process of shared decision-making may be particularly difficult for AYAs to engage in, possibly due to lower levels of health literacy. Family members of AYAs may support shared decision making about AYAs’ healthcare through distributed health literacy skills and practices. However, the nature of this process among family members is unclear.

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SYMPOSIUM 2019We conducted a systematic review of qualitative studies that aimed to explore the process of decision-making and characterised how AYA healthcare information is shared, from the perspective of the AYA or their family members.

Electronic searches using EMBASE, MEDLINE, PsycINFO and CINAHL were conducted in May 2018. Duplicates were removed and articles screened for exclusion criteria. Peer-reviewed studies discussing the decision-making process in AYAs and/or their families were eligible for inclusion, as were studies addressing information sharing, decision-making preferences, and health literacy within this group. Data was extracted and appraised by two independent raters, and findings analysed thematically using Framework analysis.

A total of 7273 studies (after removing 1801 duplicates) were screened using title and abstract. Of those, 706 full text studies were screened, resulting in a final list of 14 qualitative studies to be assessed for quality. Included studies reported the experiences of AYAs and their families in Australia, Denmark, Finland, Iran, Spain, UK and USA. Data aligned with the Supported Health Literacy Pathway model (Edwards et al., 2015) in that AYAs draw on their family members’ knowledge, skills and practices to generate informed options and make shared decisions. Barriers to AYA involvement were identified, such as being excluded from decisions by parents, clinicians discussing information/options with parents before the AYA, and clinicians using blocking behaviours during medical encounters.

To our knowledge, this is the first systematic review of family processes of information sharing and decision-making in the AYA population. Elucidating the nature of family involvement in AYAs decision-making process is warranted, as many parents/families may facilitate communication and serve as mediators to improve or compensate for AYAs health literacy skills.

An interactive web app for evaluating somatic structural variant callingTingting Gong1,2, Vanessa Hayes1,2,3,4, Eva KF Chan1,2

1 Garvan Institute of Medical Research 2 Central Clinical School, The University of Sydney 3 St Vincent’s Clinical School, The University of New South Wales 4 School of Health Systems and Public Health, University of Pretoria, South Africa

Acquired structural rearrangements play a significant role in cancer progression and tumor evolution. Accurate detection of structural variants (SV) in whole genome sequencing (WGS) analysis is influenced by many “alterable” variables, the choices of which are not always straightforward. With increasing demand for WGS analysis in a clinical setting, there is an unmet need for clinician scientist to easily make bioinformatically-driven decisions on a case-by-case for every unique patient and sample.

We aim to develop an easy-to-use tool for evaluating the effects of various variables on our ability to accurately call somatic SVs.

Firstly, the effect of the several parameters, including SV caller, sequencing depth, variant allele frequency, and required SV breakpoint resolution, on somatic SV calling from WGS were evaluated unbiasedly. Secondly, a statistical model, based on these parameters, was developed to predict sensitivity and precision of SV calling. Thirdly, a web app translating these findings into an interactive and visual platform allowing users to easily explore the effects of each, as well as the combinations, of these parameters was developed.

The web app is free to access. It has been tested on three SV callers (Manta, Lumpy and GRIDSS) with a realistic range of sequencing coverages of tumor (20x-90x) and matched normal samples (15x-90x), variant allele frequencies (5%-100%) and breakpoint precision thresholds (2bp-200bp).

We have developed an interactive web app that can help users to quickly make otherwise mundane decisions and is easily expandable to be able to include more newly developed SV callers.

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SYMPOSIUM 2019Establishing a SWATH-mass spectrometry biomarker discovery platform for comprehensive proteomics of plasma-derived extracellular vesicles for glioma tumour monitoringHallal S.1, Azimi A.2,Wei H.2,3, Shivalingam B.4, Buckland M.E2,3 and Kaufman K.L1,2,4

1 Discipline of Pathology, Sydney Medical School, The University of Sydney 2 Department of Dermatology, Westmead Hospital, The University of Sydney 3 BrainStorm Brain Cancer Research Group, Brain and Mind Centre, The University of Sydney 4 Neuropathology Department, Royal Prince Alfred Hospital, Brain and Mind Centre 5 Department of Neurosurgery, Chris O’Brien Lifehouse

Diffuse gliomas (grades II-IV) are amongst the most frequent and devastating primary brain tumours of adults. Currently, patients are monitored by neuro-radiographic assessments, which can be insensitive to early signs of treatment failure and tumour recurrence, and may not distinguish common treatment related effects from true tumour progression. Brain biopsy and histologic analysis can provide definitive diagnoses and evaluate disease progression; however serial biopsies are impractical and biopsied tissue may not reflect the heterogeneity of tumours. A minimally invasive ‘liquid biopsy’ that could sample glioma material from the blood has significant potential to improve patient care. Extracellular vesicles (EVs) encapsulate molecules that reflect the identity and molecular state of the cell-of-origin and their release is upregulated in neoplasia. EVs cross the blood-brain-barrier into the circulation and as such, hold significant promise as robust tumour biomarkers. Despite their suitability as biomarkers, a comprehensive proteome profile of circulating EVs has been hindered by the complexity and heterogeneity of the blood and presence of highly-abundant serum proteins.

To optimise a novel EV proteome profiling platform suitable for blood biomarker discovery and determine its suitability and potential for glioma tumour monitoring.

EVs were isolated by size exclusion chromatography from IDHmut astrocytoma grade II-III (n=12), IDHmut 1p19q-codeleted oligodendroglioma grade II-III (n=5), IDHwt glioblastoma (GBM; n=23), meningioma (n=5) and matched healthy (n=6) plasma (accessed from Sydney Brain Tumour Bank). Nanoparticle tracking and transmission electron microscopy confirmed the isolation of ~100nm vesicles. A comprehensive protein library database (comprising 11,316 species) was developed using peptide samples from a range of glioma specimens, including cell lysates, tumour tissues, EVs and other cancer tissues. Processed plasma EV peptides were then analysed by SWATH mass spectrometry, and the identities and absolute quantities of measured proteins were determined by aligning captured data to the custom glioma protein library using Skyline software.

We identified 4055 proteins across all plasma EV samples. Differential expression analysis identified significantly changing EV proteins between tumour subtypes and grades, including multiple proteins previously reported as markers of GBM invasion and aggression. Unsupervised cluster analyses show the potential of this proteomics platform for monitoring brain cancers via a blood test.

We have achieved the most comprehensive blood-based glioma EV proteome coverage. Glioma-associated EVs in the blood have significant potential to be used for liquid biopsies to monitor tumour progression and treatment response as well as describing diagnostic, prognostic and predictive biomarker signatures.

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SYMPOSIUM 2019MicroRNA-based therapeutics for the treatment of high-risk neuroblastomaHolly Holliday1,2, Eoin Dodson1,2, Iva Nikolic3, Niantao Deng1,2, Benjamin Elsworth1,2, Kaylene Simpson3,4, Alvin Kamili5,6, Madeleine Wheatley5, Joshua McCarroll5, Glenn Marshall7, Jamie Fletcher5, Alex Swarbrick1,2 1 Garvan Institute of Medical Research 2 St Vincent’s Clinical School, Faculty of Medicine, The University of New South Wales 3 Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre 4 Sir Peter MacCallum Department of Oncology, University of Melbourne 5 Children’s Cancer Institute, Lowy Cancer Research Centre, The University of New South Wales 6 School of Women’s and Children’s Health, The University of New South Wales 7 Sydney Children’s Hospital and Children’s Cancer Institute

Neuroblastoma is the most common extra-cranial solid cancer of childhood; typically effecting young children aged 1-5. High-risk patients have a 5-year survival rate below 50%. Treatment for these patients involves high-dose multi-layered chemotherapy, which is often not curative and causes severe health impacts later in life. There is therefore an urgent need to find alternative drugs to either replace or significantly improve upon conventional therapy. MicroRNAs (miRNA) are potent regulators of gene expression and are emerging as an exciting new class of therapeutic. However, our understanding of miRNA function in neuroblastoma is fragmented, restricting our ability to capitalise on their therapeutic potential.

To screen and validate miRNAs that sensitise neuroblastoma cells to chemotherapy in vitro. Candidate therapeutic miRNAs will then be used to treat pre-clinical models of high-risk neuroblastoma.

We have performed a functional genomic screen of >1200 miRNA mimics in the Kelly cell line, a model of poor-prognosis disease. This was performed in combination with low doses (IC30) of doxorubicin and vincristine. Pre-clinical modelling is currently being conducted in the COG-519 patient-derived xenograft model, originating from a patient with high-risk disease after several lines of treatment. We are using Star-POEGMA nanoparticles to deliver candidate miRNAs in combination with chemotherapy. Ongoing work includes short-term mechanistic experiments to assess miRNA uptake and knockdown of predicted mRNA targets, and long-term therapeutic experiments to monitor tumour size and survival.

Three miRNAs, miR-99b-5p, miR-380-3p and miR-485-3p, had potent synthetic lethal interaction with doxorubicin in vitro. These miRNAs are potentially novel tumour suppressors as they undergo recurrent copy number loss in neuroblastoma, and low expression predicts poor outcome. Excitingly, candidate miRNA miR-99b-5p can be effectively delivered into neuroblastoma PDX tumour cells by nanoparticle injection. Preliminary RNA-Sequencing analysis of miR-99b-5p-treated tumours revealed a decrease in cell cycle genes and an increase in neuronal differentiation genes.

We predict that the addition of miRNA treatment to chemotherapy will increase therapeutic outcome, while reducing the toxicity associated with conventional high-dose chemotherapy.

Development and assessment of an integrated patient information, education and support program in head and neck cancer – Comprehensive Head and Neck Cancer Education and Support (CHANCES) programJoe Jabbour1; Haryana M. Dhillon2,3; Heather L. Shepherd2,3; Puma Sundaresan1,5; Chris Milross1,4; Jonathan R. Clark1,6,7 1. Central Clinical School, The University of Sydney 2. Psycho-Oncology Cooperative Research Group (POCOG), School of Psychology, The University of Sydney 3. Centre for Medical Psychology & Evidence-Based Decision-making, The University of Sydney 4. Department of Radiation Oncology and Medical Services, Chris O’Brien Lifehouse 5. Crown Princess Mary Cancer Centre, Westmead Hospital 6. Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse 7. South West Clinical School, The University of New South Wales

Interrelated factors at the patient, provider, and information levels can have a detrimental impact on patient understanding of health information and subsequent health outcomes. We developed a comprehensive, multiformat education program for patients with head and neck cancer (HNC) and healthcare professionals (HCP) involved in their care.

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SYMPOSIUM 2019To establish a HNC information platform accessible and acceptable to HCP and patients incorporating continuous quality improvement and new evidence as it emerges.

A multi-stage development and revision process was undertaken. Stage 1: Cross-sectional stakeholder information needs survey. Stage 2: Content development: Multidisciplinary expert panel (n=20) developed content using an iterative review process. Stage 3: Multiplatform resource build; Stage 4: Usability testing; Stage 5: User acceptability testing.

In a cross sectional survey of HCP perceptions of HNC resources 112 /648 (17%) clinicians responded with 85% using written information as their primary mode of patient education. They indicated need for improved information on pain management, risk factors, survivorship and side effects. The majority (66%) indicated a preference for internet-based resources. A total of 596 patients responded to the survey of information needs, with most reported receiving sufficient information about disease process and treatment. Fewer reported information about psychosexual health (56%) or patient support groups (56%). Most patients wanted access informative via multiple modes of delivery. Information addressing 10 types of HNC from diagnosis through treatment to survivorship were developed, reviewed a minimum of three times each, and underwent assessment of readability before being finalised. Website was developed to present the information, animations, video vignettes, and downloadable information booklets. Usability assessment in 15/56 patients, 90% with high health literacy, indicate information presentation, order, and explanation of medical jargon was very clear (90%). Access to both written and electronic form as preferred by 33% of participants. Most patients (90%) felt prepared about their cancer diagnosis and treatment after reading the information resource.

The CHANCES program is an evidence-based HNC information resource acceptable, accessible, and understandable to patients and to HCP. Longer-term evaluation is required to assess its impact on health outcomes and resource use.

Bone morphogenetic signalling pathway acts at the roots of ovarian cancer chemo-resistanceGeorge Joun1, James Cornwell1,2, Anna de Fazio3,4, Naisana S. Asli1,2

1 Discipline of Oral Biosciences, School of Dentistry, Faculty of Medicine and Health, The University of Sydney, Westmead Hospital 2 Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, USA 3 Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead 4 Department of Gynaecological Oncology, Westmead Hospital 5 Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead Hospital

High Grade Serous Ovarian Carcinoma (HGSOC) is clinically characterised by therapeutic resistance to the standard of care (SOC) treatments and alarming mortality rates. Marking HGSOC is genetic and epigenetic intra-tumoural heterogeneity (ITH) leading to the development of distinct clones. Therapeutic failure has been proven in the context of tumours harbouring ITH as this mechanistically allows for the development of therapy resistant cells.

To understand how a genetic driver of HGSOC underlies ITH and subsequent therapeutic failure and success.

Single cell cloning was carried out of AOCS15 (Australian Ovarian Cancer Study) through FACS seeding of single DAPI-negative cells into each well of a 96-well plate. Single cell tracking was undertaken to characterise the clonal events of HGSOC in SOC Carboplatin and pre-clinical oncology drug prospect Dosomorphin Homologue 1 (DMH1). Droplet RNA sequencing of individual cells gave insight into the response of clonal populations to Carboplatin and DMH1 combination.

The Cancer Genome Atlas was probed for an unaddressed genetic driver in HGSOC. Components of the Bone Morphogenetic Protein (BMP) signalling pathway were amplified in up to half of HGSOC cases associating with significantly poorer survival. A commercially available preclinical specific BMP inhibitor DMH1 was tested in HGSOC cell lines COLO316 and AOCS15 with results confirming down-regulation of the canonical signalling pathway, so did monoclonal antibody interference of BMP6. DMH1 significantly improved responses to carboplatin in multiple HGSOC cell lines. The sensitising effect of DMH1 treatment came with the biomarker of increased cellular stress in the ATM/CHK2 and ATR/CHK1 pathway activation. Single cells clones, compared to un-cloned ‘Parent’ population control showed significantly heterogeneous Carboplatin responses. Strikingly, molecular analysis of Carboplatin sensitive clones further established the biomarker of elevated cellular stress present in SOC sensitive cases. In single cell tracking, HGSOC displayed low cell death under Carboplatin through lengthening the cell cycle and undergoing successful mitosis. This

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SYMPOSIUM 2019increased the population number of each clone during drug challenge resulting in rare cells reinstating successful mitosis after a seven day drug holiday. DMH1 treatment correspondingly elevated mitotic catastrophe in Carboplatin, eroded clonal populations lowering the incidence of reactivated tumour cells after the drug holiday.

Addressing an uncharacterised genomic driver of HGSOC antagonised ITH imposed therapeutic failure. This was marked by elevated cellular stress causing the depletion of clone populous, subsequently lowering the risk of highly resistant rare cells emerging from the drug challenge.

Overcoming Pgp-mediated drug-resistance by releasing lysosomal stored doxorubicin with lysosomal targeting agentsLeck LYW, Seebacher NA, Richardson DR, Jansson PJ The University of Sydney

The intracellular distribution of chemotherapeutics has been known to cause variation in the activity and selectivity of drugs. Notably, cytotoxic chemotherapeutic of the drug, doxorubicin (DOX) caused by drug transporter (e.g. P-glycoprotein, Pgp) has been observed in various Pgp-expressing subtype cells.

This study aimed to investigate the synergistic effect and mechanism of the anti-cancer agents in drug resistant Pgp-expressing cells.

This study utilized different anti-cancer agents as well as inhibiting Pgp to elucidate the synergistic effect and mechanism of these drugs in KB31 and KBV1 cervical carcinoma, MCF7 and MDA-MB-231 breast cancer, and HCT-15 colorectal adenocarcinoma cancer cell lines.

This studies demonstrated the synergistic effect between di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), or di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) with DOX. Herein, we demonstrated that both DpC and Dp44mT effectively kills Pgp expressing cancer cells, whereas DOX potently destroys non-Pgp-expressing tumour cells. The underlying mechanism involves both drugs being transported into the lysosomes through the transport activity of Pgp, where they have shown to stimulate the lysosomal-membrane permeabilization to release DOX trapped within the lysosomes. This novel approach of loading intracellular lysosomes with DOX, and subsequent permeabilization with DpC or Dp44mT causes the re-localization of DOX within the ‘safe house’ of the lysosomes to its nuclear target, where it can carry out its activity by enhancing cytotoxicity against resistant tumour cells. Indeed, the synergistic interaction between these agents can be prevented through the use of 1) pharmacological inhibitors, Elacridar; 2) Pgp silencing or; 3) lysosomal-membrane stabilization to inhibit the re-localization of DOX from lysosomes to the nucleus.

This novel strategy and potent anti-tumour efficacy observed between the thiosemicarbazones and DOX offers a promising avenue for future research and in the development of effective therapeutic treatments designed to treat advanced and resistant heterogeneous tumours in terms of P-gp expression.

Difference of reading performance of Australian and Chinese radiologists in interpreting dense breast mammogramsTong Li1, Seyedamir Tavakoli Taba1, Pek-Lan Khong2, Kriscia Tapia1, Phuong Dung Trieu1, Moayyad Suleiman1, Patrick Brennan1, Sarah Lewis1 1. BreastScreen Reader Assessment Strategy, Faculty of Health Sciences, The University of Sydney 2. Department of Diagnostic Radiology, Faculty of Medicine, The University of Hong Kong

Variations in the performance of breast readers are well reported, but key parameters explaining such variations in different countries are not fully explored. In particular, reading screening mammograms with high breast density is very challenging due to dense breast tissue masking the appearances of small lesions.

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SYMPOSIUM 2019The main aim of this study is to investigate performances of Australian and Chinese radiologists in interpreting dense breast mammographic images.

In order to assess radiologists’ performance, a mammographic test set from BreastScreen Reader Assessment Strategy (BREAST) program was used which contained 60 mammographic examinations with high breast density, simulating an environment that may be found in an Asian breast screening environment. Images were displayed on high resolution diagnostic monitors, supported by radiology workstations with full image manipulation capabilities. Thirteen Australian and twelve Chinese and radiologists reviewed all the cases in the test set independently. Radiologists were asked to identify and localise all lesions in the examinations and provide a confidence rating from 1 to 5 to each lesion. Case sensitivity, specificity, lesion sensitivity, receiver operating characteristic area under the curve (ROC AUC) and jack-knife free-response receiver operating characteristic figure of merit (JAFROC FOM) were used to assess radiologists’ performances. Demographic information and clinical reading experience were also collected from the readers. Mann-Whitney U tests were used to compare results between the two populations and discover the relationship of reader performances with reading experience.

For radiologists who were less than 40-year-old, lesion sensitivity (p = 0.04), AUC (p =0.03) and JAFROC (p = 0.04) were significantly lower in Chinese radiologists than those in Australian. Australian radiologists with less than 10 years of reading experience had higher AUC and JAFROC scores compared with their Chinese counterparts (p = 0.04 and p = 0.02, respectively).

We found that younger Australian radiologists performed better at reading dense breast cases which is likely to be linked to intensive fellowship training, immersion in a screening program and exposure to the benefits of a performance-measuring education tool. We believe our preliminary findings provide an initial understanding of breast diagnosis in Chinese radiologists and their differences from Australian.

Are melanoma patients willing to accept the risks of adjuvant immunotherapy treatment to receive the benefits?Ann Livingstone1,2, Anupriya Agarwal1, Martin R. Stockler1,2,3, Alexander M. Menzies4,5, Kirsten Howard2, Rachael L. Morton1,5, 1 NHMRC Clinical Trials Centre, The University of Sydney 2 School of Public Health, The University of Sydney 3 Central Clinical School, The University of Sydney 4 Northern Clinical School, The University of Sydney 5 Melanoma Institute Australia

Adjuvant anti-PD-1 immunotherapy for resected stage III and IV melanoma patients improves disease-free survival, however is costly and incurs toxicity. Little is known about treatment preferences for patients or clinicians in the adjuvant setting, or the factors melanoma patients are willing to accept to obtain survival benefits.

To identify factors important to patients and clinicians when making a decision or a recommendation about adjuvant immunotherapy for treatment of resected melanoma.

A systematic review of quantitative and qualitative studies of patient and clinician preferences for adjuvant immunotherapy in melanoma, was conducted in the following databases: Medline, EMBASE, ECONLIT, PsychINFO and the COCHRANE Systematic Reviews from inception to June 2018. Findings were tabulated and described in a narrative synthesis.

Eight studies from the USA, Germany and Australia met the eligibility criteria, and included nivolumab, ipilimumab, pembrolizumab and interferon immunotherapies. All study designs were cross sectional and included three discrete choice experiments, three standard gamble surveys and two focus group studies. Ten factors important to decision making were identified including: overall survival, treatment side effects (including fatigue, diarrhoea, skin and immune system toxicities, hypophysitis), drug delivery (mode of delivery, treatment frequency and duration) and recurrence-free survival. The most important factor for patients and clinicians was overall survival. Patients were willing to tolerate significant toxicities for minimal survival gains. The transparency of reporting of studies was assessed according to STROBE and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Research

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SYMPOSIUM 2019Practices for Conjoint Analysis. Overall, studies were clearly reported, however, some studies were limited by omission of key factors such as common immunotherapy side effects, skin and immune system toxicities (over and under active thyroid gland, liver and lung inflammation).

Our review suggests, when making decisions about adjuvant immunotherapy, quantity not quality of life is most important to stage II-IV melanoma patients. This research will inform and facilitate patient-centred adjuvant immunotherapy treatment decision making. Future research is required to explore preferences for different combinations of immunotherapy, durations of treatment, and potential long-term side effects.

HIF-1 is activated in colorectal cancer in a cell culture model of obstructive sleep apnoeaChloe-Anne Martinez, Bernadette Kerr, Peter Cistulli, Kristina Cook Charles Perkins Centre, Faculty of Medicine and Health, Northern Clinical School, The University of Sydney

Obstructive sleep apnoea (OSA) affects 5-20% of the population and has been linked with an increased risk of cancer development and increased rate of cancer-related mortality. OSA is characterised by episodic upper airway obstruction during sleep, leading to systemic intermittent hypoxia. Animal models of OSA-like intermittent hypoxia show increased tumour growth and metastasis, implying that intermittent hypoxia is a critical driver of tumour progression. Advanced tumours typically have regions of chronic hypoxia, which is known to activate the transcription factor hypoxia inducible factor-1 (HIF-1). HIF-1 controls the expression of many cancer-related genes, and patients with increased HIF-1 generally have a worse cancer prognosis. Intermittent hypoxia from OSA is proposed to increase HIF-1 activity in affected tissues, including tumours in the body. However, there are a lack of appropriate cell-based models of OSA to substantiate this.

To determine whether HIF-1 is activated in tumour cells in intermittent hypoxia mimicking OSA.

We have developed an experimental cell-based model that simulates tissue oxygenation in OSA. In this, cultured cells are plated onto gas-permeable membranes and are exposed to rapid alternating oxygen levels. Following exposure, changes in mRNA and protein expression are examined using quantitative real-time PCR and western blotting. Initial studies have been conducted on a HCT116 colorectal cancer cell line.

Intermittent hypoxia increases HIF-1α protein levels leading to the activation of HIF-1 in HCT116 cells. HIF-1 transcriptional activity leads to the upregulation of a hypoxic gene expression signature which is associated with a poorer prognosis and higher resistance to chemotherapy. The level of expression of this hypoxic signature correlated with that in cells exposed to a sustained dose of 3% O2, averaged from the oxygen curve produced by our intermittent hypoxia protocol. This suggests that the change in gene expression is determined by the total dose of hypoxia rather than the frequency of hypoxia-reoxygenation cycles per se. Moreover, levels of HIF1A mRNA are increased in intermittent hypoxia when compared to chronic hypoxia, suggesting differential HIF-1α regulation at the transcriptional level.

The activation of HIF-1 in tumour cells exposed to systemic intermittent hypoxia may be key to understanding how OSA increases cancer development and progression, as observed in human and animal studies. OSA-mediated activation of HIF-1 in an early stage tumour (i.e. one that has not yet developed regions of chronic hypoxia) may have significant adverse sequelae.

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Mammographic breast density of Japanese women living in Australia: Implication for breast screening policyMiwa M Mizukoshi, Syeda Z Hossain, Ann Poulos, Patrick Brennan The Faculty of Health Sciences, The University of Sydney

Mammographic Breast Density (MBD) increases breast cancer risk, lowers sensitivity of screening mammography and is related to ethnicity.

This study compared the MBD of Australian women living in Australia (AW), Japanese women living in Japan (JWJ) and Japan-born women living in Australia (JWA). The outcomes provide implications for breast screening policies for Japanese migrant women in Au

In this cross-sectional study, a total 677 women’s mammographic images were collected. Of them Australia-born women (N=203) and Japan-born women residing in Australia (N=202) were from BreastScreen NSW and Japanese women living in Japan (N=272) were from Miyata Hospital, Japan, during 2014-2015. The MBDs were retrospectively evaluated using the fifth edition Breast Imaging-Reporting and Data System (BI-RADS) to assess the level of MBD. The readers assess MBD based on the what extent parenchymal tissue can mask an underly breast cancer. This assessment is reported using four categories; a. almost entirely fatty, b. scattered fibroglandular densities, d. heterogeneously dense, and d. extremely dense. The categories a. and b. are combined as high MBD and c. and d. are defined as low MBD. Descriptive analysis and binary logistic regression were performed to compare the Odds Ratios (OR) of the different study population and age groups.

The results showed that more than 65% of AW were found in low MBD category while the majority of JWJ were in the high MBD category. The MBD of JWA showed a similar pattern as those who reside in Japan but a slightly lower MBD. AW aged 40-49 were categorised to as low MBD (62%), which was almost similar to those aged 50-59 (67%). Whereas, a great majority of JWA aged 40-49 were found into high MBD (80%) compared to women aged 50-59 (65%). However, JWJ were categorised as high MBD regardless of their age. The ORs demonstrated that JWA were approximately 5 times more likely and JWJ were about 15 times more likely to have high MBD when compared to AW.

The data suggests that screening mammography for AW aged 40-49 could be highly effective as the MBD for this groups demonstrate a similar pattern to women aged 50-59. JWA and JWA, on the other hand, have high MBD, therefore supplemental screening is recommended to improve screening outcomes. Further robust evidence of the harms and benefits obtained by supplemental screening for high MBD is warranted.

Older adults’ preferred and perceived roles in decision-making about palliative chemotherapy, their decision priorities, and information preferencesErin B Moth1,2, Belinda E Kiely1,3,4, Andrew Martin4, Vasikaran Naganathan2,5,6, Stephen Della-Fiorentina3,7, Florian Honeyball8, Rob Zielinski9, Christopher Steer10, Hiren Mandaliya3, Abiramy Ragunathan3, Prunella Blinman1 1. Concord Cancer Centre, Concord Repatriation General Hospital 2. Concord Clinical School, The University of Sydney 3. Macarthur Cancer Therapy Centre, Campbelltown Hospital 4. National Health and Medical Research Council, The University of Sydney 5.Centre for Education and Research on Ageing, Concord Clinical School, The University of Sydney 6. Ageing and Alzheimer’s Institute, Concord Repatriation General Hospital 7. Southern Highlands Cancer Centre 8. Alan Coates Cancer Centre, Dubbo Base Hospital 9. Central West Cancer Centre, Orange 10. Border Medical Oncology, Albury

People with cancer have varied preferences for involvement in decision-making ranging from active, through collaborative and passive roles. Effective treatment decision-making requires an understanding of these role preferences, as well as patients’ priorities and information needs.

We sought older adults’ preferred and perceived roles in decision-making about palliative chemotherapy; their

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SYMPOSIUM 2019decision-making priorities; and information received and desired.

Patients aged ≥65 years with incurable cancer who had discussed palliative chemotherapy with an oncologist and made a decision about whether or not to receive palliative chemotherapy were invited to complete a written questionnaire. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale (CPS). Associations with preferred decision-making role were examined using Wilcoxon rank sum tests. Factors important in making a decision about chemotherapy, and receipt of and desire for information were described.

The 179 respondents had a median age of 74 years (range 65 to 92 years). Most were male (114, 64%) and had chosen to receive chemotherapy (148, 83%). Half (92, 52%) were vulnerable by the Vulnerable Elders Survey-13 (score ≥3). Preferred decision-making roles (n=173) were active in 39%, collaborative in 27%, and passive in 35%. Perceived decision-making roles (n=172) were active in 42%, collaborative in 22%, and passive in 36%, and matched the preferred role for 63% of patients. Preference for an active role was associated with being single/widowed (p=0.004, OR 1.49) and declining chemotherapy (p=0.02, OR 2). Factors ranked most important when making a decision about chemotherapy (n=159) were “doing everything possible” (30%), “my doctor’s recommendation” (26%), “my quality of life” (20%), and “living longer” (15%). A minority expected chemotherapy to cure their cancer (14%). Most had discussed expectations of cure (70%), side effects (88%) and benefits (82%) of chemotherapy, though fewer had received quantitative prognostic information (49%) than desired this (67%).

Older adults showed varied preferences for involvement in decision-making about palliative chemotherapy, and most played the role that they preferred. To facilitate shared decision-making, oncologists should seek patients’ decision-making preferences, priorities and information needs when discussing palliative chemotherapy.

Quality of life in the initial 100 cases of cytoreductive surgery and heated intraperitoneal chemotherapy at the Royal Prince Alfred HospitalHeidi Mueller, Nabila Ansari, Cherry Koh, Daniel Steffens Surgical Outcomes Research Centre (SOuRCe)

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex abdominal operation involving a combination of tumour resection and heated intraperitoneal chemotherapy (HIPEC) administered directly into the abdominal cavity during the operation to target residual microscopic cancer cells. This procedure has been shown to significantly improve survival and potentially cure patients with colorectal or appendiceal peritoneal metastases. In early 2017, the second state-wide CRS & HIPEC service in New South Wales (NSW) was established at the Royal Prince Alfred Hospital (RPAH). Most research in this patient cohort to date presents clinical information, though little information is available about the patient experience and quality of life (QoL).

The aim of the current study was to describe the short-term QoL outcomes up to 12-months post-operatively of the first 100 CRS & HIPEC cases at RPAH.

The Peritonectomy Surgical Research Program (PREMIER) is a prospective cohort study based at RPAH. All patients undergoing CRS & HIPEC are invited to participate in this study, which involves collecting patient demographic, clinical and QoL data. Participants complete a QoL assessment pre-operatively (baseline), upon hospital discharge, and at 3, 6 and 12 months post-operatively. QoL was assessed using the well-validated Short Form-36 version 2 (SF36v2) instrument. Patient responses were scored according to the instrument specific scoring methods and mean scores (standard deviation) of the patient cohort for both health components are presented.

The patient cohort is predominately from metropolitan NSW, over 50 years of age at surgery, diagnosed with colorectal cancer, and gender is nearly evenly split. Preoperatively, both the mean physical and mental health component scores are similar. At discharge, mean mental health component scores remained similar to baseline though mean physical health score decreases substantially. This returns to near baseline by 3 months post-operative, and both mental and physical health component scores remain constant at 6 and 12 months post-operative.

Our major findings are that both mental and physical health QoL scores return to baseline by 3-months post-surgery and remain constant thereafter. Though only the first 100 patients were included in the current study, this provides

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SYMPOSIUM 2019valuable information for clinicians and patients to use during decision making prior to undertaking this surgery. Longer-term outcomes are expected as the PREMIER program matures. These findings may be used to identify specific patient groups likely to require increased support post-operatively, or who may be at risk of poor QoL outcomes following this complex, radical cancer surgery.

Personalised medicine approach in pancreatic cancer reveals fine-tuned stromal FAK manipulation improves global response the gemcitabine and Abraxane while sensitising circulating tumour cells to shear stress in transitKendelle J. Murphy1, Morghan C. Lucas1, Claire Vennin1, James R.W. Conway1, Sean C. Warren1, Joanna N. Skhinas1, Max Nobis1, Cecilia R Chambers1, Daniel Reed1, Ashleigh Parkin1, Romain Bidanel1, Astrid Mangneau1, Lisa Horvath1, Yingxiao Wang1, Jennifer P. Morton4, Owen Sanson4, Thomas R. Cox1,2, Marina Pajic1,2, David Herrmann1,2, Paul Timpson1,2 1. Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Cancer Division 2. St Vincent’s Clinical School, Faculty of Medicine, The University of New South Wales 3. Institute of Engineering in Medicine, University of California, San Diego, USA 4. Cancer Research UK, Beatson Institute, Glasgow, UK

Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second leading cause of cancer mortality by 2030. Current standard-of care gemcitabine/Abraxane is only marginally improved over previous monotherapy regimes, which are generally ineffective in this aggressive treatment-refractory disease. PDAC development occurs in a complex microenvironment, where extensive stromal desmoplasia alters mechanical tumour-stromal interactions promoting tumour progression and metastatic spread.

Here we aim to fine-tune stromal manipulation using targeted therapies on a stratified and personalised basis in order to improve the efficiency of current standard-of-care therapies.

Intravital imaging of the FUCCI cell cycle reporter and parallel Second Harmonic Generation (SHG) imaging of collagen fibres at primary and secondary sites, was used to systematically demonstrate cell response to standard-of-care therapy whilst also visualising extracellular matrix (ECM) manipulation respectively. To assess the response of cells to FAKi, we measured real time treatment response in vivo with a Förster resonance energy transfer (FRET) biosensor for FAK activity. To complement our in vivo metastatic studies we used both primary PDAC cell lines and patient-derived xenograft cell lines in 2D and 3D in vitro models of invasion, anchorage-independent growth and shear-stress assays to streamline treatment regimes.

Parallel Intravital imaging of the FUCCI reporter and SHG of collagen, at primary sites demonstrated that fine-tuned FAKi decreases ECM remodelling and also alters cell cycle progression improving standard-of-care response. Further imaging at secondary niches revealed manipulation by FAKi inhibition also sensitises cells to in transit, enhancing treatment efficacy whilst also reducing metastatic spread. Furthermore stratified patient samples suggest a subset of patients likely to response to fine-tuned FAKi schedules.

This fine-tuned stromal manipulation may allow us to maximise gemcitabine/Abraxane therapy whilst reducing drug toxicity and potentially reducing further metastatic spread in patients.

Subcellular specific targeting of JNK as a novel anti-metastatic therapy in triple negative breast cancerJeremy ZR Han1, Jordan F Hastings1, Antonia Cadell1, Dushan Miladinovic1, Yolande O’Donnell1, Ben Parker2, Adelaide Young1, Samantha Oakes1,3, Thomas R Cox1,3, David R Croucher1,3

1. The Kinghorn Cancer Centre, Garvan Institute of Medical Research 2. Charles Perkins Centre, The University of Sydney 3. St Vincent’s Hospital Clinical School, The University of New South Wales

Triple negative breast cancer (TNBC) has a much poorer prognosis than hormone receptor or HER2 positive breast

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SYMPOSIUM 2019cancer, due in part to a higher relapse rate and frequent metastasis to the pleura, lung, liver and brain. Targeted therapies towards receptor tyrosine kinases such as EGFR and MET have shown promising initial responses, followed by rapid relapse. As such, chemotherapy remains the standard of care for patients. Instead of targeting individual molecules at the top of signaling pathways, our lab has focused on inhibiting the key nodes that integrate signaling from many potential oncogenes. To this end we have identified JNK as a critical oncogenic signaling node in TNBC, downstream of multiple oncogenic pathways, capable of promoting proliferation, invasion and metastasis. In normal breast tissue JNK activity is mostly observed in the nucleus, however both the loss of nuclear JNK and the gain of cytoplasmic JNK is frequently observed in breast cancer tissue. Due to the necessity of JNK for normal processes such as tumour suppression and chemotherapy response, systemically targeting JNK is unlikely to yield successful translation to the clinic.

The aim of this project was to develop effective tools for characterising the opposing functional and prognostic roles of JNK in vitro and in vivo, in order to target the signaling complex that is essential for propagating oncogenic JNK activity.

This project will made use of patient cohorts, and genetically encoded localization-specific JNK inhibitors within three-dimensional cell culture models and in vivo metastasis assays. By adapting our recently published, interaction-based proteomic platform (Croucher et al., Science Signaling, 2016) we specifically isolated and characterised the oncogenic, cytosolic JNK complex.

JNK exists as two spatially separate network states; a tumour suppressing, nuclear JNK pool, and an oncogenic, cytosolic JNK pool. Nuclear JNK activity controls cell polarity in 3D assays and can be lost due to upstream mutations in MAP2K4 and MAP3K1. Cytoplasmic JNK promotes growth and inhibits apoptosis due to loss of adhesion, while also promoting metastatic outgrowth in vivo. Cytoplasmic JNK activity is activated through a MAP3K1:MKK7 signaling complex formed on the cell cytoskeleton.

Our lab has demonstrated that two distinct JNK network states exist simultaneously within breast cancer cells. By targeting the MAP3K1:MKK7 signaling complex we can specifically inhibit the oncogenic form of JNK, without disturbing the tumour suppressing function of nuclear JNK activity. This finding opens up novel therapeutic options for targeting this critical oncogenic signaling node in TNBC.

Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitroBrooke A. Pereira1, Natalie L. Lister1, Kohei Hashimoto2, Linda Teng1, Maria Flandes-Iparraguirre3, Angelina Eder3, Alvaro Sanchez-Herrero3, Birunthi Niranjan1, Melbourne Urological Research Alliance (MURAL)4, Mark Frydenberg1,5,6, Melissa M. Papargiris1

1. Prostate Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University 2. Department of Urology, Sapporo Medical University School of Medicine, Japan 3. Centre in Regenerative Medicine, Institute of Health & Biomedical Innovation, Queensland University of Technology 4. Melbourne Urological Research Alliance (MURAL) 5. Department of Surgery, Monash University 6 Australian Urology Associates, Melbourne 7. Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre 8. Department of Physiology, Biomedicine Discovery Institute, Monash University 9. ARC Centre in Additive Biomanufacturing, Queensland University of Technology 10. School of Health and Wellbeing, University of Southern Queensland 11. Sir Peter MacCallum Department of Oncology, The University of Melbourne

The tumour microenvironment (TME) plays a fundamental role in prostate carcinogenesis. Classical tumour recombination experiments have shown that cancer-associated fibroblasts (CAFs) and their aberrant extracellular matrix (ECM) alone can direct tumour formation in benign epithelia. Despite this, CAFs remain poorly characterised and are often overlooked in human prostate cancer (PCa) models. Similarly, little is known about the role of infiltrating immune cells in early PCa, with the literature indicating both pro- and anti-tumourigenic effects. Previous studies have

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SYMPOSIUM 2019implicated mast cells in PCa, a resident immune population which expands with increasing tumour grade and can recruit other immune components to the prostatic TME.

To better understand the role of CAFs, their ECM and mast cells, we developed a three-dimensional (3D) bioengineered TME microtissue in vitro model which interrogates the interaction and contribution of these components on early prostate tumourigenesis.

Melt-electrospun scaffolds were formatted from medical grade poly(ε-caprolactone). Patient-derived primary CAFs or non-malignant prostatic fibroblasts (NPFs) were incorporated into the scaffolds, forming 3D microtissues. Once confluent, tagged benign epithelial cells (BPH-1 or RWPE-1) were co-cultured on the microtissues ± mast cell (MC; HMC-1 or LAD2), MC-conditioned media (CM) or recombinant tryptase. Subsequently, microtissues were fixed and tumourigenicity was assessed by analysing the 3D morphological transformation of epithelial cells.

Our data show that CAF and NPF proliferate and each deposit distinct ECM to form a 3D stromal network within the scaffolds. We have shown that CAF, but not NPF, microtissues induce an invasive morphology in the benign epithelium. MCs cooperate with CAFs, potentiating CAF-induced tumourigenic effects. These effects are mediated by MC secreted factors, specifically tryptase (a serine protease). Our data indicate that MC-derived tryptase acts, in part, by remodelling the native aberrant ECM deposited by primary CAFs, conferring tumourigenicity on the benign epithelia.

Overall, this model demonstrates the cascade of interactions between CAFs, ECM and MCs, mediated by tryptase, to drive early epithelial transformation in the human prostate. Our data also highlight tryptase as a key mediator of these effects, which may be a therapeutic target in prostate carcinogenesis.

Retrotransposon activity in young patients with oral squamous cell carcinoma (OSCC)L Satgunaseelan1, M Gauthier2, M Cowley2, K Lo3, J Yang3, J Clark4,5, R Gupta1,4,5

1. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospita 2. Children’s Cancer Institute Australia 3. Sydney Bioinformatics and Biometrics, School of Mathematics and Statistics, University of Sydney 4. Central Clinical School, University of Sydney 5. Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse

A recent alarming increase in the incidence of OSCC has been seen in young patients in the absence of tobacco or alcohol use, or HPV integration. Retrotransposons are mobile DNA elements which have been shown to have a role in cancer, particularly LINE-1, with transposition events resulting in mutagenesis.

To compare the activity of three retrotransposon families (LINE-1, SVA and Alu) between young (<45) and older patients with OSCC.

7 young and 14 older non-HPV OSCC patients, whose genomes were sequenced at high depth, were identified from The Cancer Genome Atlas (TCGA). The Mobile Element Locator Tool (MELT) was employed to detect non-reference retrotransposon events in the selected genomes.

The total count of putative somatic LINE-1 insertions was significantly higher in the young as compared to the older cohort (p=0.004). In addition, the total count of putative germline LINE-1 insertions was significantly higher in the young as compared to the older cohort (p=0.002). A significantly higher number of these events were found to occur close to genes (p=0.019), with possible roles in cancer predisposition syndromes (e.g. OR4C45 and DTNB). RNA-Seq data from TCGA is being analysed to assess the potential impact of the insertions on gene expression. We are also evaluating their presence in our own cohort of 22 OSCC patients from Chris O’Brien Lifehouse, for which we have performed whole genome and RNA sequencing.

The presence of elevated LINE-1 activity in young patients in both the somatic and germline settings may shed light on the increasing development of OSCC at an early age. Retrotransposons may represent a predisposing factor in young patients, with detection of retrotransposon activity a potential future biomarker of OSCC.

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GPs and melanoma: How Australian GPs make sense of their role at the front line of melanoma careSmith AL1, Robinson S2, Watts CG2,3, Schmid H4,5, Thompson J4,6, Scolyer R4,6,7, Spillane A4,6, Gyorki D8,9, Mar, V10,11,12, Morton RM4,13, Mann GJ4,5, Cust AE2,4

1. Australian Institute of Health Innovation, Macquarie University 2. Cancer Epidemiology and Prevention Research, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney 3. Surveillance, Epidemiology and Prevention Program, Kirby Institute, The University of New South Wales 4. Melanoma Institute Australia (MIA), The University of Sydney, Australia 5. Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney 6. Sydney Medical School, The University of Sydney, Sydney 7. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital 8. Peter MacCallum Cancer Centre 9. Department of Surgery, University of Melbourne 10. Victorian Melanoma Service, The Alfred 11. Department of Epidemiology and Preventive Medicine, Monash University 12. Skin and Cancer Foundation Inc. 13. NHMRC Clinical Trials Centre, The University of Sydney,

In Australia, melanoma is managed in both the primary and secondary care settings and can involve care from specialists, general practitioners (GPs) or a combination of both. An individual concerned about a suspicious lesion typically presents first to their GP.

To explore how GPs make sense of their role in the prevention, diagnosis and treatment of melanoma in primary care in Australia.

Data were generated through in-depth semi-structured interviews (October 2018 to February 2019) with 21 GPs (male: 10; female: 11) working in a range of settings (independent GPs: 10; medical centre practice: 8; skin cancer clinic: 2; government clinic: 1). Data analysis was by thematic analysis.

The overlapping roles that GPs and specialists (dermatologists and surgeons) can play in melanoma care creates a unique set of challenges for GPs. In particular, the GP has to decide which patients they are prepared to diagnose, treat and monitor and which patients they will refer on to a specialist clinician. GPs in this study reported considerable variation in their level of comfort and confidence in diagnosing and treating melanoma patients. Factors identified as influencing how GPs negotiate their role in melanoma care were categorised as being melanoma-related, GP-related, patient-related and contextual.

Given the increasing burden of melanoma in Australia, it is likely GPs will continue to play an integral role in melanoma management. It may therefore be important to consider how GPs can be supported to further develop their skills and confidence in the diagnosis and treatment of melanoma. It may also be useful to clarify points at which referral of the patient to specialist care is warranted.

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Factors associated with length of stay in patients undergoing upper gastrointestinal cancer surgeryClare Toms1, Daniel Steffens1,3, David Yeo1,2,4, Charbel Sandroussi1,2,3,4

1. Surgical Outcomes Research Centre (SOuRCe), The University of Sydney & Sydney Local Heath District 2. Institute of Academic Surgery (IAS), Royal Prince Alfred Hospital (RPAH) 3. Faculty of Medicine and Health, The University of Sydney 4. Department of Hepatobiliary and Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital (RPAH)

Length of stay (LOS) in cancer patients is influenced by factors including their age, extent of disease and their procedure.

The aim of this study was to (i) describe the characteristics of consecutive upper gastrointestinal (UGI) surgical patients at the Royal Prince Alfred Hospital; and (ii) examine potential factors that could influence their length of hospital stay.

Patients undergoing primary, recurrent or metastatic UGI cancer surgery between January 2016 and December 2018 were investigated. Length of hospital stay (including Intensive Care Unit and Ward) was dichotomised into short stay (≤14 days) and long stay (≥14 days). Main outcomes included patient characteristics (i.e. primary/recurrent tumour, Charlson Comorbidity Index (CCI), neoadjuvant chemoradiation, age, preoperative intervention) and surgical outcomes (i.e. operative method and complications). A univariate analysis was performed to investigate if patient characteristics and surgical outcomes would predict length of hospital stay.

A total of 399 patients underwent surgery with a positive UGI cancer diagnosis within the study period. Of these, 344 (61.2%) were male with an average age of 66 years, 333 (83.5%) patients had a primary UGI cancer, of which 201 (60.4%) were hepatobiliary in nature. Most patients had a preoperative intervention prior to surgery (83.5%) and 18.3% had a post-operative complication. The mean LOS was 13 days, with patients presenting oesophageal cancers having the longest LOS (19 days, p=0.006). Open surgery (OR= 5.2; 95%CI=2.3 to 11.8; p=0.00) and post-operative complications (OR= 3.0; 95%CI=1.7 to 5.4; p=0.00) were found to be significant indicators of prolonged length of stay. CCI, age and preoperative intervention approached but did not reach significance.

Open surgery and postoperative complications were factors associated with a longer LOS for patients undergoing UGI cancer surgery.

Geographic variation in time to diagnosis and treatment of oral cavity and oropharynx cancer in NSWRebecca L Venchiarutti1,2, Jonathan R Clark 1,3,4, Carsten E Palme1,3,4, Thomas P Shakespeare5, Jacques Hill5, Abdul Rahim Mohd Tahir6, Patrick Dwyer1,7, Jane M Young1,2,3

1. The University of Sydney, Faculty of Medicine and Health 2. Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital and the University of Sydney 3. RPA Institute of Academic Surgery, Sydney Local Health District 4. Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse 5. Department of Radiation Oncology, Mid North Coast Cancer Institute 6. Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour Health Campus 7. Department of Radiation Oncology, Northern NSW Cancer Institute

Head and neck cancer (HNC) is a complex disease requiring well-coordinated multidisciplinary care to optimise patient outcomes and for which geographical variation in outcomes have been described in NSW previously. These variations may be caused by longer times to diagnosis and treatment of HNC.

To examine geographic variations the time intervals along the pathway to treatment among HNC patients in NSW.

A retrospective cohort study was conducted at two tertiary referral centres based in metropolitan and regional NSW. Eligibility criteria were: primary oropharynx or oral cavity squamous cell carcinoma (SCC), NSW resident, diagnosis between 01/07/2008 and 30/06/2013, treatment with curative intent, and aged ≥18 years at diagnosis. Main outcome measures were time from diagnosis to treatment and time from surgery to post-operative radiotherapy. The proportion

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SYMPOSIUM 2019of patients meeting timeframes in the Optimal care pathway for people with head and neck cancers (OCP-HNC) was assessed.

A total of 224 patients were eligible (140 living in metropolitan NSW and 84 living in regional/remote NSW). There were equal numbers of patients with oropharynx and oral cavity cancer (n=112 in each group). Median time from symptom onset to treatment was longer for regional/remote patients with oropharynx SCC (4.7 v 3.8 months, p = 0.044) and oral cavity SCC (6.4 v 3.3 months, p=0.003). Median time from diagnosis to treatment was also longer for regional/remote patients with oropharyngeal SCC (47 days v 36 days, p=0.003). Time from surgery to adjuvant radiotherapy was longer among regional/remote patients with oral cavity SCC (66 v 42 days, p=0.001). The proportion of patients commencing adjuvant radiotherapy within six weeks of surgery (OCP-HNC recommendation) was higher among patients treated at a metropolitan site (51%) compared to those treated at a regional centre (14%, p=0.018).

Regional/remote HNC patients experience longer times to diagnosis and treatment compared metropolitan patients, however adherence to optimal timeframes was generally poor regardless of remoteness of residence. Our findings suggest improvements in timeliness of diagnosis and treatment can be made for all patients with HNC in NSW, and that patients living in regional NSW may experience different barriers to timely diagnosis and treatment than those in metropolitan NSW. Our findings have formed the basis of an ongoing prospective study investigating specific facilitators and barriers to early diagnosis and treatment of HNC, the results of which may inform changes to health policy and practice to reduce clinical variation and improve outcomes for HNC patients regardless of residence.

Long term pain and fatigue following pelvic exenterationKenneth Vuong1, Michael Solomon1,2,3, Cherry Koh1, Lyndal Alchin1, Jane Young1,2,3, Daniel Steffens1,2 1. Surgical Outcomes Research Centre (SOuRCe), The University of Sydney & Sydney Local Health District 2. Faculty of Medicine and Health, The University of Sydney 3. The Institute of Academic Surgery at Royal Prince Alfred Hospital, Sydney Local Health District

Pelvic Exenteration (PE) is a radical surgery offering patients with locally advanced or recurrent cancer confined within the pelvis, the best chance of survival as the only form of “curative” treatment. To date, most of the PE literature focuses on investigating survival and quality of life (QoL) outcomes. Few studies investigate the clinical course of common preoperative and postoperative symptoms, such as pain, which is often described as the main trigger for PE patients to seek medical care and fatigue, one of the common side effects of colorectal cancer and its treatment.

The aim of this study is to determine the long-term course of pain and fatigue in patients undergoing pelvic exenteration.

A prospective cohort study was conducted at Royal Prince Alfred Hospital including consecutive patients undergoing pelvic exenteration surgery between July 2008 and December 2017. Consenting patients completed a patient reported outcome measures questionnaire before surgery and post-operatively at 6, 12, 18, 24, 30, 36, 48 and 60 months. Data up until March 2019 was included in the analysis. Pain and fatigue trajectories were described throughout the study period. Higher scores indicate worst pain and fatigue outcomes. Paired t test was used to investigate changes in pain and fatigue scores from baseline.

A total of 466 patients underwent PE for locally advanced or recurrent cancer and were included in this study. The highest pain (48/100) and fatigue scores (54/100) were reported preoperatively. Although scores were lower at each subsequent time-point when compared to preoperatively, this was only statistically significant at 18 (MD: 6.6; 95%CI: 0.8 to 12.4; p=0.026), 36 (MD:9.0; 95%CI: 0.9 to 17.1) and 48 (MD: 10.3; 95%CI: 1.0 to 19.7) months for pain and 12 (MD:3.9; 95%CI: 0.4 to 7.4), 18 (MD:5.2; 95%CI: 0.9 to 9.5) and 48 (MD: 6.8; 95%CI: 0.3 to 13.2) months post-operatively for fatigue.

This study demonstrates that patients undergoing pelvic exenteration report high levels of pain and fatigue preoperatively. During the postoperative period, pain and fatigue seems to ease with time, however symptoms are reported during the 5-year follow-up.

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The development of a metal-based complex with anti-metastatic activity in breast cancer cells in vitroAndria May Yaourtis, Aviva Levina, Peter Lay The University of Sydney

Cancer metastasis is the leading cause of death amongst cancer patients. Previous work from our research group has demonstrated that treatment of MDA-MB-231 cells (a highly aggressive human breast cancer cell line in vitro) with a metal-complex induces a morphological change in these cells, shifting them from a metastatic phenotype to a less aggressive one.

The aim of our research was to investigate the molecular mechanisms underlying the change in morphology of MDA-MB-231 cells after treatment with a metal-complex, and to characterise and quantify the extent and type of morphological change. Furthermore, we

MDA-MB-231 cells were treated with a sub-toxic concentration of the metal- complex, and after 72 hours confocal laser scanning microscopy (CLSM) with immunofluorescence was used to characterise protein biomarkers for metastatic and epithelial cells. Scratch wound assay was used to determine changes in migratory and invasive properties in the treated cells. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to determine changes in the surface topography and ultrastructure of cells. Further, isoelectric cell focusing (ICF) was used to investigate the effects of the metal complex on a cell signalling pathway that is significant in cancer.

CLSM revealed changes in cell parameters including volume and surface area of cells post treatment, and SEM further confirmed an enlargement and flattening of these cells. Scratch wound assay indicated that the treatment reduced migratory and invasive properties of the cancer cells. Furthermore, changes in protein phosphorylation indicating changes in the cell signalling cascade was evident with ICF.

This study provides a promising novel drug that has the ability to change the phenotype of aggressive metastatic cancer cells to a less invasive one, with a reduction in migratory and invasive properties. The development of a drug targeting cancer metastasis will have profound clinical implications in the treatment of highly aggressive cancers.

Physical activity for women with metastatic breast cancer: a randomised feasibility trialJasmine Yee1, Glen M Davis1, Daniel Hackett1, Jane M Beith2, Nicholas Wilcken3, David Currow4, Jon Emery5,6, Jane Phillips7, Andrew Martin8, Rina Hui3, Michelle Harrison2, Eva Segelov9, Sharon L Kilbreath1

1. Faculty of Health Sciences, The University of Sydney 2. The Chris O’Brien Lifehouse 3. Crown Princess Mary Cancer Centre, Westmead Hospital, The University of Sydney 4. Faculty of Health Sciences, Flinders University 5. General Practice and Primary Care Academic Centre, University of Melbourne 6. General Practice, University of Western Australia 7. Faculty of Health, University of Technology Sydney 8. Clinical Trials Centre, University of Sydney 9. Monash Health and Monash University

Physical activity for women with early breast cancer is well recognised for managing cancer-related symptoms and improving quality of life. Whilst typically excluded from interventions, women with metastatic breast cancer may also benefit from physical activity.

This study explored the i) safety and feasibility of a partially-supervised, home-based physical activity program for women with metastatic breast cancer and ii) preliminary efficacy of the intervention.

Fourteen women aged 62.2 ± 10.6 y and 3.5 ± 4.2 y after diagnosis of metastatic breast cancer were randomised to a control or intervention arm. The intervention comprised an 8-week program of 16 supervised resistance training sessions at the participant’s home and an unsupervised walking program. The control group was asked to maintain

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SYMPOSIUM 2019their habitual level of physical activity. Safety and feasibility were determined through recruitment and retention rates, adherence and adverse events. All participants completed the six-minute walk test (6MWT) and FACIT-Fatigue at baseline and following the intervention.

Amongst 15 eligible participants, 14 consented to participate, generating a recruitment rate of 93% to the study. Adherence to the resistance and walking components of the program was 100% and 25%, respectively. No serious adverse events were reported. When the mean scores from baseline to post-intervention were compared, trends in favour of exercise over control were observed for 6MWT distance (+40 ± 23m vs. -46m ± 56m, respectively; Glass’s delta=0.154) and FACIT-Fatigue score (+5.6 ± 3.2 vs. -1.8 ± 3.9, respectively; Glass’s delta=1.92).

A partially-supervised, home-based physical activity program for women with metastatic breast cancer was feasible and did not result in any adverse events. The dose of the resistance training component was well-tolerated and achievable. In contrast, adherence and compliance to the unsupervised walking program was poor. Preliminary data suggest a physical activity program may lead to improvements in physical capacity. There is a need for future research to identify safe and optimal exercise parameters.

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SYMPOSIUM 2019

UPCOMING EVENTS

SOCIAL MEDIA FOR RESEARCHERS WORKSHOP

Hosted by Associate Professor Haryana Dhillon Tuesday 16 July 2019 11.00 - 1.00pm University of Sydney Registrations open

DC DOWN UNDER 2019 - IMMUNOLOGY & CANCER

Wednesday 31 July 2019 5.00pm for 6.00 - 9.00pm Level 5 Education Centre, Chris O’Brien Lifehouse Missenden Road, Camperdown Registrations open

SYDNEY CATALYST INTERNATIONAL TRANSLATIONAL CANCER RESEARCH SYMPOSIUM 2019

Thursday 19 September 2019 9.00am - 5.00pm The Garvan Institute of Medical Research Darlinghurst Registrations open

Keynote speakers and International Guests:• Professor Galina Velikova, The University of Leeds, UK• Professor Margart Tempero, The University of California, USA• Professor Ian Harris, Universities of New South Wales and Sydney• Professor Derek Raghavan, Levine Cancer Institute

To register for our events visit - https://www.sydneycatalyst.org.au/events/syd-cat-upcoming-events.aspx

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SYMPOSIUM 2019

Proudly Supported by:

SYDNEY CATALYST INTERNATIONAL TRANSLATIONAL CANCER RESEARCH SYMPOSIUM From Bench to Bedside and Beyond

REGISTRATIONS NOW OPENRegistration: Member $110 | Non member $150

Professor Galina Velikova

Professor Derek Raghavan

Thursday 19 September 2019The Garvan Institute of Medical Research

Hosted by Professor Michael Boyer & Featuring International Guests

Professor Margaret Tempero

Professor Ian Harris

postgraduate & early career researcher symposium …€¦ · our experienced panellists will...

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