Hunter Cancer Research Alliance
As a multidisciplinary and multi-institutional alliance, the Hunter Cancer Research Alliance (HCRA) functions to provide capacity building, funding and strategic support to cancer research across the translational research continuum – from basic research through clinical trials to behavioural, implementation and health services research.
With the support of our partnering institutions, executive leaders and a membership that consists of 250+ cancer-focused researchers, we are working to promote the excellence of cancer research in the Hunter and ultimately improve cancer patient outcomes in our region and beyond.
Journal: Implementation Science
Designing an implementation intervention with the Behaviour Change Wheel for health provider smoking cessation care for Australian Indigenous pregnant women
Gillian S. Gould, Yael Bar-Zeev, Michelle Bovill, Lou Atkins, Maree Gruppetta, Marilyn J Clarke and Billie Bonevski
Background: Indigenous smoking rates are up to 80% among pregnant women: prevalence among pregnant Australian Indigenous women was 45% in 2014, contributing significantly to the health gap for Indigenous Australians. We aimed to develop an implementation intervention to improve smoking cessation care (SCC) for pregnant Indigenous smokers, an outcome to be achieved by training health providers at Aboriginal Medical Services (AMS) in a culturally competent approach, developed collaboratively with AMS.
Method: The Behaviour Change Wheel (BCW), incorporating the COM-B model (capability, opportunity and motivation for behavioural interventions), provided a framework for the development of the Indigenous Counselling and Nicotine (ICAN) QUIT in Pregnancy implementation intervention at provider and patient levels. We identified evidence-practice gaps through (i) systematic literature reviews, (ii) a national survey of clinicians and (iii) a qualitative study of smoking and quitting with Aboriginal mothers. We followed the three stages recommended in Michie et al.’s “Behaviour Change Wheel” guide.
Results: Targets identified for health provider behaviour change included the following: capability (psychological capability, knowledge and skills) by training clinicians in pharmacotherapy to assist women to quit; motivation (optimism) by presenting evidence of effectiveness, and positive testimonials from patients and clinicians; and opportunity (environmental context and resources) by promoting a whole-of-service approach and structuring consultations using a flipchart and prompts. Education and training were selected as the main intervention functions. For health providers, the delivery mode was webinar, to accommodate time and location constraints, bringing the training to the services; for patients, face-to-face consultations were supported by a booklet embedded with videos to improve patients’ capability, opportunity and motivation.
Conclusions: The ICAN QUIT in Pregnancy was an intervention to train health providers at Aboriginal Medical Services in how to implement culturally competent evidence-based practice including counselling and nicotine replacement therapy for pregnant patients who smoke. The BCW aided in scientifically and systematically informing this targeted implementation intervention based on the identified gaps in SCC by health providers. Multiple factors impact at systemic, provider, community and individual levels. This process was therefore important for defining the design and intervention components, prior to a conducting a pilot feasibility trial, then leading on to a full clinical trial.
Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia
S Degryse, CE de Bock, S Demeyer, I Govaerts, S Bornschein, D Verbeke, K Jacobs, S Binos, DA Skerrett-Byrne, HC Murray, NM Verrills, P Van Vlierberghe, J Cools and MD Dun
Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens.
Journal: Physics in Medicine & Biology
Virtual EPID standard phantom audit (VESPA) for remote IMRT and VMAT credentialing
Narges Miri, Joerg Lehmann, Kimberley Legge, Philip Vial and Peter B Greer
A virtual EPID standard phantom audit (VESPA) has been implemented for remote auditing in support of facility credentialing for clinical trials using IMRT and VMAT. VESPA is based on published methods and a clinically established IMRT QA procedure, here extended to multi-vendor equipment. Facilities are provided with comprehensive instructions and CT datasets to create treatment plans. They deliver the treatment directly to their EPID without any phantom or couch in the beam. In addition, they deliver a set of simple calibration fields per instructions. Collected EPID images are uploaded electronically. In the analysis, the dose is projected back into a virtual cylindrical phantom. 3D gamma analysis is performed. 2D dose planes and linear dose profiles are provided and can be considered when needed for clarification. In addition, using a virtual flat-phantom, 2D field-by-field or arc-by-arc gamma analyses are performed.
Pilot facilities covering a range of planning and delivery systems have performed data acquisition and upload successfully.
Advantages of VESPA are (1) fast turnaround mainly driven by the facility's capability of providing the requested EPID images, (2) the possibility for facilities performing the audit in parallel, as there is no need to wait for a phantom, (3) simple and efficient credentialing for international facilities, (4) a large set of data points, and (5) a reduced impact on resources and environment as there is no need to transport heavy phantoms or audit staff. Limitations of the current implementation of VESPA for trials credentialing are that it does not provide absolute dosimetry, therefore a Level I audit is still required, and that it relies on correctly delivered open calibration fields, which are used for system calibration.
The implemented EPID based IMRT and VMAT audit system promises to dramatically improve credentialing efficiency for clinical trials and wider applications.
- Nicholas Zdenkowski, George Radvan, Leanna Pugliese, Julie Charlton, Christopher Oldmeadow, Allison Fraser, Antonino Bonaventura (2017). Treatment of pancreatic insufficiency using pancreatic extract in patients with advanced pancreatic cancer: a pilot study (PICNIC). Supportive Care in Cancer.
- Benoni Boilly, Sam Faulkner, Phillip Jobling, and Hubert Hondermarck (2017). Nerve Dependence: From Regeneration to Cancer. Cancer Cell.
- James R. Perry, Normand Laperriere, Christopher J. O’Callaghan, Alba A. Brandes, Johan Menten, Claire Phillips, Michael Fay. et al (2017). Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma. New England Journal of Medicine.
- Aldo Scarpa, David K. Chang, Katia Nones, Christopher J. Scarlett et al (2017). Whole-genome landscape of pancreatic neuroendocrine tumours. Nature