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: Radiation Oncology
A remote EPID-based dosimetric TPS-planned audit of centers for clinical trials: outcomes and analysis of contributing factors
Miri N, Legge K, Colyvas K, Lehmann J, Vial P, Moore A, Harris M, Greer PB.
Background. A novel remote method for external dosimetric TPS-planned auditing of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for clinical trials using electronic portal imaging device (EPID) has been developed. The audit has been applied to multiple centers across Australia and New Zealand. This work aims to assess the audit outcomes and explores the variables that contributed to the audit results. Methods.Thirty audits were performed of 21 radiotherapy facilities, 17 facilities underwent IMRT audits and 13 underwent VMAT audits. The assessment was based on comparisons between the delivered doses derived from images acquired with EPIDs and planned doses from the local treatment planning systems (TPS). Gamma pass-rate (GPR) and gamma mean value (GMV) were calculated for each IMRT field and VMAT arc (total 268 comparisons). A multiple variable linear model was applied to the GMV results (3%/3 mm criteria) to assess the influence and significance of explanatory variables. The explanatory variables were Linac-TPS combination, TPS grid resolution, IMRT/VMAT delivery, age of EPID, treatment site, record and verification system (R&V) type and dose-rate. Finally, the audit results were compared with other recent audits by calculating the incidence ratio (IR) as a ratio of the observed mean/median GPRs for the remote audit to the other audits. Results. The average (± 1 SD) of the centers' GPRs were: 99.3 ± 1.9%, 98.6 ± 2.7% & 96.2 ± 5.5% at 3%, 3 mm, 3%, 2 mm and 2%, 2 mm criteria respectively. The most determinative variables on the GMVs were Linac-TPS combination, TPS grid resolution and IMRT/VMAT delivery type. The IR values were 1 for seven comparisons, indicating similar GPRs of the remote audit with the reference audits and > 1 for four comparisons, indicating higher GPRs of the remote audit than the reference audits. Conclusion. The remote dosimetry audit method for clinical trials demonstrated high GPRs and provided results comparable to established more resource-intensive audit methods. Several factors were found to influence the results including some effect of Linac-TPS combination.
Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence
Ben Sang, Yuan Yuan Zhang, Su Tang Guo, Ling Fei Kong, Qiong Cheng, Guang Zhi Liu, Rick F. Thorne, Xu Dong Zhang, Lei Jin, and Mian Wu
Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc–mediated cell proliferation and Mcl-1–mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)–mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.
Electronic nicotine devices to aid smoking cessation by alcohol- and drug-dependent clients: protocol for a pilot randomised controlled trial
Ashleigh Guillaumier, Victoria Manning, Olivia Wynne, Coral Gartner, Ron Borland, Amanda L. Baker, Catherine J. Segan, Eliza Skelton, Lyndell Moore, Ramez Bathish, Dan I. Lubman and Billie Bonevski
Background. Up to 95% of people entering treatment for use of alcohol or other drugs (AOD) smoke tobacco. Smokers receiving treatment for AOD use are interested in quitting and make quit attempts, but relapse is more common and rapid compared with the general population of smokers. New ways to address smoking in this population are needed. Electronic nicotine devices (ENDs) or electronic cigarettes hold significant potential as both cessation aids and harm reduction support. This study focuses on the potential of ENDs to facilitate smoking cessation and to sustain it in the medium term among people in treatment for AOD use. The aim of this trial is to explore the effectiveness, feasibility and acceptability of ENDs for smoking cessation compared with combination nicotine replacement therapy (NRT) for clients after discharge from a smoke-free AOD residential withdrawal service. Methods/design. The study is a pragmatic randomised controlled trial. In total, 100 participants will be recruited following admission to a smoke-free residential withdrawal service in Melbourne, Australia. Participants will complete a baseline survey and be randomised to either the END group (n = 50) or the NRT group (n = 50) prior to discharge. Both groups will receive telephone counselling support from quitline. Follow-up measures will be assessed at 6 and 12 weeks following discharge. The primary outcome is continuous abstinence from smoking at 12 weeks post discharge. Secondary outcomes include: 7-day point prevalence from smoking, point prevalence abstinence from all nicotine (including NRT and ENDs), cravings and withdrawal, time to relapse, and treatment adherence (use of NRT, ENDs and quitline). Discussion. This is the first randomised controlled trial to assess the effectiveness and acceptability of ENDs within a population dependent on AOD, a priority group with very high levels of smoking. The research will test a model of how to incorporate novel smoking cessation support into a period of high treatment receptiveness.
Journal: Journal of the National Comprehensive Cancer Network
Single-Arm Longitudinal Study to Evaluate a Decision Aid for Women Offered Neoadjuvant Systemic Therapy for Operable Breast Cancer
Nicholas Zdenkowski, Phyllis Butow, Andrew Spillane, Charles Douglas, Kylie Snook, Mark Jones,Christopher Oldmeadow, Sheryl Fewster,Corinna Beckmore, Frances M. Boyle, for the Australia and New Zealand Breast Cancer Trials Group
Background. Neoadjuvant systemic therapy (NAST) is an increasingly used treatment option for women with large operable or highly proliferative breast cancer. With equivalent survival outcomes between NAST and up-front surgery, the situation-specific preference-sensitive nature of the decision makes it suitable for a decision aid (DA). This study aimed to develop and evaluate a DA for this population. Methods. A DA booklet was developed according to international standards, including information about adjuvant and neoadjuvant treatment, outcome probabilities, and a values clarification exercise. Eligible women, considered by investigators as candidates for NAST, were enrolled in a multi-institutional, single-arm, longitudinal study. Patient-reported outcome measure questionnaires were completed pre- and post-DA, between chemotherapy and surgery, and at 12 months. Outcomes were feasibility (percentage of eligible patients accessing the DA); acceptability to patients (percentage who would recommend it to others) and clinicians (percentage who would use the DA in routine practice); and decision-related outcomes. Results. From 77 eligible women, 59 were enrolled, of whom 47 (79.7%; 95% CI, 69.4–89.9) reported having read the DA; 51 completed the first post-DA questionnaire. Of these 51, 41 participants (80.4%; 95% CI, 69.5–91.3) found the DA useful for their decision about NAST. Of 18 responding investigators, 16 (88.9%; 95% CI, 74.4–103.4) indicated they would continue to use the DA in routine practice. Post-DA, decisional conflict decreased significantly (P<.01); anxiety and distress decreased significantly; and 86.3% (95% CI, 73.7–94.3) achieved at least as much decisional control as they desired. Conclusions. This DA was feasible and acceptable to patients and clinicians, and improvement in decision-related outcomes was demonstrated when used in combination with clinical consultations. This DA could safely be implemented into routine practice for women considering NAST for operable breast cancer.