Oral abstracts

toms, core beliefs, and social support. RESEARCH IMPLICATIONS: This research allows a better understanding about the effects of a group intervention specifically designed to promote the PTG. Furthermore, the assessment of PTG and other psychosocial variables, over the three measurement points, is an important contribution to scientific knowledge, since is according to the current socialcognitive theoretical model of PTG. CLINICAL IMPLICATIONS: The assessment of the efficacy of group intervention to facilitate PTG, as it is described in the present study, may encourage the application and inclusion of this intervention group in the hospitals’ multidisciplinary health care, usually provided to Portuguese women with breast cancer. ACKNOWLEDGEMENT OF FUNDING: This study was funded by a Portuguese Foundation for Science and Technology (SFRH/ BD/81515/2011).


EPHA2 ANTIBODY INCREASES SENSITIVITY OF U87 GLIOBLASTOMA CELLS TO IRRADIATION
Michael Fay 1,2,3 , Jennette Sakoff 2,4 , Jennifer Martin 2,4 Stephen Rose 5,6 , Stuart Crozier 5 , Andrew Boyd 5,7 , Klaus Dittman 3 , Hans-Peter Rodemann 3 1. Genesis Cancer Care, Australia 2. Calvary Mater Hospital, Newcastle, Australia 3. Eberhard Karls Universität, Tübingen, Germany 4. University of Newcastle, Newcastle, Australia 5. University of Queensland, Brisbane, Australia 6. Biomedical Imaging, Health and Biosecurity,CSIRO,Brisbane,Australia 7. Queensland Institute of Medical Research,Herston,Brisbane,Australia Background: Glioblastoma is a poor prognosis brain tumour with median survival typically around a year. EphA2 is a membrane bound tyrosine kinase thought to be important in mediating cell-to-cell interactions. An imbalance in EphA2 signalling appears to be associated with a particularly malignant phenotype in glioblastoma patients. Our research team has developed a monoclonal antibody that specifically targets EphA2 with the purpose of investigating the ability of this antibody to synergise with adjuvant radiation treatment.

Aims:
To investigate the cytotoxicity in glioma cells of a specific EphA2 antibody when given with radiotherapy.
Methods: U87 glioma cells were chosen for study as they are known to express EphA2 and grow readily in cell culture. U87 glioma cells were treated with EphA2 antibody or an isotype control IgG and treated with 2Gy 16h later and assessed for colony formation after 2 weeks using Comassie blue staining. Western blotting strategies were also exploited to investigate the content of EphA2 in glioma cells following treatment.
Results: Treatment of glioma cells with EphA2 antibody significantly reduced the content of EphA2 and phosphorylated EphA2 in glioma cells, within 16h. Treatment of glioma cells with EphA2 antibody alone had minimal effect on the growth of cells, however, when used in combination with radiotherapy the ability of glioma cells to form colonies decreased by 80% (radiation plus EphA2). This effect was significantly greater than the effect of radiotherapy alone (50% reduction), indicative of a synergistic interaction.

Conclusions:
We have shown that pre-radiation treatment with EphA2 antibody leads to a markedly decreased colony forming ability in glioma cells. We intend to expand upon this data and investigate the role of this tyrosine kinase in radiation sensitivity with the purpose of exploring this therapy in the clinical arena.
Translational research aspect: This is a T1/T2 translational project. Background: Patient-experience tools have not been designed specifically to inform health service change. Use of this data as a quality improvement mechanism has proven difficult with limited effects. To provide clear and actionable improvement messages, detailed evidence on patients' preferences and priorities for service change is needed.

AIMING FOR THE RIGHT QUALITY IMPROVEMENT TARGET: CROSS-SECTIONAL DATA EXPLORING OUTPATIENTS' PRIORITIES AND PREFERENCES FOR QUALITY IMPROVEMENT IN TERTIARY CLINICS
Aims: To report the: proportion of outpatients selecting each general quality improvement initiative; detailed initiatives corresponding to commonlyselected (>10%) general initiatives; and, commonly-selected initiatives in order of relative priority.

Methods:
Outpatients completed a touch-screen survey in three tertiary clinics, including two medical oncology clinics. Participants selected up to 23 general initiatives that would improve in-clinic experiences. Using novel survey software, participants could select an additional 110 detailed initiatives and complete relative prioritization exercises.
Results: A total of 541 outpatients participated (71.1% consent, 73.1% completion), including 336 (62.0%) oncology outpatients. In order of relative priority, examples of commonly-selected general initiatives included: up-to-date information provision (15.0%); access to information at home (12.8%); reduced wait-times (19.8%); and information on medical emergencies (11.1%). To address general initiatives, 40 detailed initiatives were selected. For example, to improve up-to-date information provision, participants selected: providing information on treatment steps (72.8%) and condition progress when possible (67.9%); and, to receive test results quickly (58.0%). Participants selected access to a list of trust-worthy sources (45.1%) to improve information provision at home. To manage medical emergencies, participants selected information on emergency symptoms (71.7%) and information for family (61.7%) as specific initiatives.
Conclusions: Information-based initiatives were commonly-selected and are of relatively greater perceived priority. Improved wait-times was commonly selected but was a relatively lower priority.
Translational research aspect (T3): Using this survey approach, patients are able to specify and prioritise strong quality improvement preferences. This data provides clear improvement messages and assists health services to strategically allocate resources to changes of greatest value to patients.

THE TOBACCO SMOKING PROFILE OF CLIENTS ATTENDING A MEDICALLY SUPERVISED INJECTING CENTRE
Eliza Skelton 1 , Billie Bonevski 1 , Flora Tzelepis 1 , Anthony Shakeshaft 2 , Ashleigh Guillaumier 1 , William Wood 3 , Marianne Jauncey 3 1. The University of Newcastle 2. National Drug and Alcohol Centre [NDARC] The University of New South Wales 3. Sydney Medically Supervised Injecting Centre Background: Medically supervised injecting centres offer a professionally supervised environment that is legally sanctioned for clients to inject preobtained illicit drugs. Among people who inject drugs (PWIDs), the rate of smoking exceeds 80% making this population particularly susceptible to tobacco-related illnesses and in need of intervention. The Medically Supervised Injecting Centre (MSIC) may be a potential setting to address tobacco smoking among PWIDs.

Aims:
The aim of this study is to examine MSIC clients' tobacco smokingrelated behaviours.
Methods: An online cross-sectional survey was conducted in November 2015 to January 2016. Eligible individuals were current MSIC clients aged ≥18years, self-reported tobacco smokers, who had satisfactory English comprehension and were able to provide informed consent.
Results: Of the 214 eligible individuals, 202 consented to participate (94%); 200(99%) were daily smokers who were moderately to heavily nicotine dependent (n = 156, 77%). Most (n = 186, 83%) had made at least one quit attempt in their lifetime. Previous quit attempts were largely unaided relying mostly on will power (n = 52, 70%). The majority (n = 138, 68%) indicated that they would like to quit smoking and would like to receive access to smoking cessation strategies while at a MSIC.
Conclusions: MSIC clients are highly nicotine dependent, interested in quitting smoking and would like their smoking to be addressed.

Translational research aspect:
This research will provide novel information to shape program development for smoking cessation care in MSICs. This is T1 research. Background: The application of in vivo dosimetry using electronic portal imaging device (EPID) has been clinically implemented to improve the quality of treatment in external beam radiotherapy (EBRT). EBRT is a complex radiation treatment technique, which uses non-intuitive fluences, and a large dose can be delivered to the patient. The traditional and routine quality assurance (QA) programs are used to prevent treatment errors. However, the main drawback of most of the QA programs used in the clinic is that they are unable to detect some serious errors during treatment, such as patient anatomy changes, data transfer issues, accidental plan modification, wrong patient position setup, failed dose delivery, and immobilization issues. We developed and clinically implemented an EPID-based real-time patient treatment verification, comparing predicted EPID image to measured EPID image in real-time. Our proposed system can ensure the quality of radiation treatments.

Aims:
The aims of this study are to develop statistically based evaluation tools for error detection during real-time EPID-based patient treatment verification for IMRT and VMAT based on verification results.

Methods:
The real-time verification system (Watchdog) utilises a comprehensive physics-based model to generate a series of predicted transit cine EPID image as a reference data set, and compares these to measured cine-EPID images acquired during treatment. The agreement between the predicted and measured transit images is quantified using chi-comparison (currently 4%,4 mm) on a cumulative frame basis.
Cine-EPID images were acquired from the first two fractions of 137 IMRT patients to generate the lower control limit using Statistical Process Control (SPC) technique; 82 Prostate treatments, 37 head and neck treatments, and 18 Rectum treatments. An action limit was determined based on an integration of real-time verification result and the calculation of process capability index. The action limit sensitivity were tested to ensure the system is able to detect patient position misalignment, dose delivery errors, wrong patient treatment, and wrong plan. For clinical study, 15 IMRT Patients were treated and operated with Watchdog used to evaluate the treatment outcome as well as to determine the source of error.

Results:
The derived lower control limits (4%,4 mm) after 2 seconds of image acquisition for prostate, head and neck, and rectum IMRT were 75.62%, 71.29%, and 71.11% respectively. For a clinical study of 15 patients, on average 7% of the entire treatment failed under the action limit and were identified for further investigation regarding the source of error (see figure a). A case study of a head and neck patient (see figure b), showed an error detected toward the end of the treatment course that was correlated with weight loss shown on CBCT scans.

Conclusions:
We have developed an evaluation method for a real-time EPID based treatment verification system (Watchdog). These action limits are designed to be applied to real-time verification during treatment with immediate intervention during SBRT treatments and post-delivery investigation during standard fractionation. Initial results found that the system detected significant changes in patient contour due to weight loss for a head and neck treatment.

Hunter Medical Research Institute
Background: Myelodysplastic syndromes (MDS) are heterogeneous groups of primary bone marrow disorders characterized by ineffective or reduced blood cell production. Supportive management comprising of blood transfusion is still the corner stone of the management of MDS. Around 80% of patients with myelodysplasia develop anaemia at diagnosis or during the course of the disease and will need a transfusion. Hypomethylating agents like azacitidine has been developed with the aim of reducing the transfusion burden and hence the risk of transfusion associated complications. Clinical trials have shown efficacy of azacitidine in reducing the frequency of blood transfusions but the benefit has not been established outside clinical trials.

Aims: Evaluation of usage and change in frequency of blood products in
Hunter area since the availability of azacitidine for treatment in MDS.

Methods:
A cross sectional study of 256 transfusion dependent MDS patients from 1 st January 2008 to 31 st May 2015 has been undertaken at the haematology department Mater hospital. Patients have been divided into groups as per treatment with or without azacitidine. Blood transfusion data has been collected from the blood bank at Pathology north for assessment.

Results:
The analysis has shown reduction in the blood transfusion frequency in transfusion dependent MDS patients. However, it has been demonstrated that reduction in blood transfusion is not a sustained response and after six to eight months of azacitidine, the requirement for blood product increases again.

Conclusions:
Azacitidine reduces the blood transfusion burden after commencement secondary to improvement of bone marrow function. However this response is not sustained and with continuation of treatment this response is lost. This phenomenon has not been demonstrated in the clinical trials.
Translational research aspect: this project is T2 research as it will help to further structure the blood bank according to the requirements of the patients to reduce the wastage of blood products. Our study results need confirmation from larger prospective studies in the future.

PREDICTORS OF MDT REVIEW AND THE IMPACT ON LUNG CANCER SURVIVAL FOR HNELHD RESIDENTS TREATED IN THE PUBLIC SECTOR
Elizabeth Tracey 1 , Sanjiv Gupta 2 , Denise Kaminski 3 , Peter Troke 3 , Anthony Proietto 3 1. University of Newcastle 2. Calvary Mater Hospital 3. Cancer Services Directorate Hunter New England LHD Background: Review by an MDT has been shown to lead to increased rates of surgical resection, radiotherapy, chemotherapy and timeliness of care. Most recently, the Victorian lung cancer patterns of care study have found that MDT review is an independent predictor of lung cancer survival.

To examine predictors of lung cancer MDT 2. To determine if MDT review is an independent predictor of survival
Methods: Hunter New England residents diagnosed with lung cancer between January 1 st 2009 and June 30 th 2013 obtained from the Clinical Cancer Registry linked to MDT surveys obtained from ARIA. Logistic regression was used to estimate predictors of MDT review and proportional hazards regression modelling was used to analyse survival.
Results: Of the 2,167 individuals with lung cancer 411 or 20% were reviewed at the MDT. The odds of MDT review were higher for stage II patients; if cytological or histologically verified; four times more likely if treated at Calvary Mater or John Hunter; if undergoing radiotherapy and if seen by a specialist nurse. Lower odds of MDT review occurred for patients with stages III and IV, or unstaged; those referred to Palliative Care and those who died within a month of diagnosis. MDT review was found to be an independent predictor of survival with a 21% lower hazard of death (HR 0.79 95% CI 0.20-0.90) after adjustment for covariates. Further stratification by stage showed that stage III patients had the most marked survival advantage HR (0.59 95%CI 0.45-0.77) followed by stage IV with a 20% reduction in the hazard of death HR (0.80 95%CI 0.66-0.97).
Conclusions: Current guidelines recommend that all lung cancer patients be reviewed at an MDT given that this is not feasible Translational research aspect (T3) targeting stage III patients would appear to confer the greatest survival advantage. Background: Therapeutic drug monitoring (TDM) is being considered to individualize cancer treatment with tyrosine kinase inhibitors like sunitinib. However, TDM's potential benefit for eligible patients in terms of clinical outcomes, such as time to tumor progression (TTP), remains unclear.

Aims:
To estimate the expected improvement of TTP from a TDM program in patients with gastrointestinal stromal tumors (GIST) treated with sunitinib at a starting dose of 37.5 mg/day.

Methods:
A Monte-Carlo simulation of 10,000 patients was performed, using published models of the pharmacokinetics and pharmacodynamics of sunitinib. The simulation included two TDM-guided dose increases of 12.5 mg/day on day 21 and 42, for patients with total (sunitinib + metabolite SU12662) trough levels (TTL) below the pharmacokinetic target of 50 ng/ml.

Results:
Without TDM, only 45.3% of patients had a TTL of at least 50 ng/ml, but two rounds of TDM increased this proportion to 76.2%. The TDM program increased median time to tumour progression in initially underdosed patients from 214 to 285 days.

Conclusions:
This simulation study does not take dose-limiting toxicity into account; in a clinical setting, not all patients will tolerate a TDM-guided dose increase. However, this Monte-Carlo simulation study suggests that an improvement in time to tumor progression might be achieved with TDM in underdosed patients that tolerate dose increases. many of the genes listed on commercial panels knowledge about disease frequency in affected populations compared to control populations is lacking thereby undermining the veracity of breast cancer susceptibility claims.
To help address the shortfall in information about some of the more recently identified genetic risk factors to breast cancer we undertook a study of 2000 cases and 2000 controls to estimate the prevalence of mutations in a panel of genes that are commonly included in commercial testing. The results reveal that MPS panel testing must continue under a research setting so that more information can be gathered to understand what is meant by the term "genetic predisposition" to breast cancer for a large proportion of genes that are currently under scrutiny. At present only four genes can be used unequivocally in a diagnostic setting for the assessment of genetic risk of disease in most countries. Background: Differences in cancer incidence and mortality are associated with inequalities at each step in the process of preventing or developing cancer, diagnosis and care provision. Patient perspectives are an important part of gaining a full understanding of how the care continuum operates. These data can assist us in identifying priority opportunities for change.

PATIENT PERSPECTIVES ON ISSUES OF ACCESS TO CANCER CARE ACROSS THE CARE CONTINUUM
This presentation will explore Australian data regarding patient perspectives on their access to care from the prevention of cancer, to obtaining a diagnosis and treatment. Data regarding perceptions on the quality of care received, preferences for change, affordability and financial impacts of cancer will be described.
An understanding of these issues allows us to consider where our research efforts might focus in order to translate evidence into practice in an equitable way and deliver a more equitable and patient-centred care.