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McKay M.J.,University of Sydney | Goh S.K.,Peter MacCallum Cancer Center | McKay J.N.,Monash University | Chao M.,Genesis Cancer Care | McKay T.M.,Deakin University
Annals of Translational Medicine | Year: 2017

Background: Clinical radiosensitivity is a significant impediment to tumour control and cure, in that it restricts the total doses which can safely be delivered to the whole radiotherapy population, within the tissue tolerance of potentially radiosensitive (RS) individuals. Understanding its causes could lead to personalization of radiotherapy. Methods: We screened tissues from a unique bank of RS cancer patients for expression defects in major DNA double-strand break repair proteins, using Western blot analysis and subsequently reverse-transcriptase polymerase chain reaction and pulsed-field gel electrophoresis. Results: We hypothesized that abnormalities in expression of these proteins may explain the radiosensitivity of some of our cancer patients. The cells from one patient showed a reproducibly consistent expression reduction in two complex-forming DNA double-strand break repair protein components (DNA Ligase IV and XRCC4). We also showed a corresponding reduction in both gene products at the mRNA level. Additionally, the mRNA inducibility by ionizing radiation was increased for one of the proteins in the patient's cells. We confirmed the likely functional significance of the non-homologous end-joining (NHEJ) expression abnormalities with a DNA double strand break (DNA DSB) repair assay. Conclusions: We have identified a novel biological phenotype linked to clinical radiosensitivity. This is important in that very few molecular defects are known in human radiotherapy subjects. Such knowledge may contribute to the understanding of radiation response mechanisms in cancer patients and to personalization of radiotherapy. © Annals of Translational Medicine.


PubMed | University of Liverpool, Radiation Oncology, Queensland University of Technology and Genesis Cancer Care
Type: | Journal: Journal of medical radiation sciences | Year: 2017

Interest in the application of yoga for health benefits in western medicine is growing rapidly, with a significant rise in publications. The purpose of this systematic review is to determine whether the inclusion of yoga therapy to the treatment of breast cancer can improve the patients physical and psychosocial quality of life (QoL).A search of peer reviewed journal articles published between January 2009 and July 2014 was conducted. Studies were included if they had more than 15 study participants, included interventions such as mindfulness-based stress reduction (MBSR) or yoga therapy with or without comparison groups and had stated physical or psychological outcomes.Screening identified 38 appropriate articles. The most reported psychosocial benefits of yoga therapy were anxiety, emotional and social functioning, stress, depression and global QoL. The most reported physical benefits of yoga therapy were improved salivary cortisol readings, sleep quality and lymphocyte apoptosis. Benefits in these areas were linked strongly with the yoga interventions, in addition to significant improvement in overall QoL.The evidence supports the use of yoga therapy to improve the physical and psychosocial QoL for breast cancer patients with a range of benefits relevant to radiation therapy. Future studies are recommended to confirm these benefits. Evidence-based recommendations for implementation of a yoga therapy programme have been derived and included within this review. Long-term follow-up is necessary with these programmes to assess the efficacy of the yoga intervention in terms of sustainability and patient outcomes.


PubMed | University of Nottingham, University of Lausanne, University of Bern, Mayo Medical School and 11 more.
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2015

Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB.Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age 18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors.The study included 107 patients (mean [standard deviation, SD] age, 69.6 [10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7).The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.


PubMed | St Vincents Hospital, University of New South Wales, The Surgical Center, Genesis Cancer Care and University of Houston-Victoria
Type: | Journal: BioMed research international | Year: 2015

Treatment of pelvic lymph nodes (PLNs) in higher risk prostate carcinoma is controversial. The primary focus of the study was to evaluate the early toxicity profile for this cohort of patients treated with Volumetric Modulated Arc Therapy (VMAT).Patient, tumour, and treatment characteristics of those who received VMAT from May 2010 to December 2012 were analysed. A simplified contouring process of the PLNs to the aortic bifurcation was developed based on consensus guidelines. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were documented according to the Radiation Therapy Oncology Group (RTOG) Version 2 Guidelines. Successive Prostate Specific Antigen (PSA) values after treatment were measured on average 3 months apart.113 patients were treated between May 2010 to December 2012 with a median follow-up of 14 months. No patients experienced acute grade 3 or 4 GU and GI toxicity. Only 1 patient experienced a late grade 3 GU complication. No late grade 4 GU or GI events have yet occurred.This study reviews the first Australian experience of VMAT in the treatment of pelvic lymph nodes in prostate cancer, specifically to the level of the aortic bifurcation. It demonstrates a favorable acute toxicity profile whilst treating large PLN volumes with optimal dose coverage.


Cormie P.,Edith Cowan University | Galvao D.A.,Edith Cowan University | Spry N.,Edith Cowan University | Spry N.,Sir Charles Gairdner Hospital | And 12 more authors.
BJU International | Year: 2015

Objective: To determine if supervised exercise minimises treatment toxicity in patients with prostate cancer initiating androgen-deprivation therapy (ADT). This is the first study to date that has investigated the potential role of exercise in preventing ADT toxicity rather than recovering from established toxicities. Patients and Methods: Sixty-three men scheduled to receive ADT were randomly assigned to a 3-month supervised exercise programme involving aerobic and resistance exercise sessions commenced within 10 days of their first ADT injection (32 men) or usual care (31 men). The primary outcome was body composition (lean and fat mass). Other study outcomes included bone mineral density, physical function, blood biomarkers of chronic disease risk and bone turnover, general and prostate cancer-specific quality of life, fatigue and psychological distress. Outcomes were compared between groups using analysis of covariance adjusted for baseline values. Results: Compared to usual care, a 3-month exercise programme preserved appendicular lean mass (P = 0.019) and prevented gains in whole body fat mass, trunk fat mass and percentage fat with group differences of -1.4 kg (P = 0.001), -0.9 kg (P = 0.008) and -1.3% (P < 0.001), respectively. Significant between-group differences were also seen favouring the exercise group for cardiovascular fitness (peak oxygen consumption 1.1 mL/kg/min, P = 0.004), muscular strength (4.0-25.9 kg, P ≤ 0.026), lower body function (-1.1 s, P < 0.001), total cholesterol: high-density lipoprotein-cholesterol ratio (-0.52, P = 0.028), sexual function (15.2, P = 0.028), fatigue (3.1, P = 0.042), psychological distress (-2.2, P = 0.045), social functioning (3.8, P = 0.015) and mental health (3.6-3.8, P ≤ 0.022). There were no significant group differences for any other outcomes. Conclusion: Commencing a supervised exercise programme involving aerobic and resistance exercise when initiating ADT significantly reduced treatment toxicity, while improving social functioning and mental health. Concurrent prescription of supervised exercise when initiating ADT is therefore advised to minimise morbidity associated with severe hypogonadism. © 2014 The Authors. BJU International © 2014 BJU International.


Awad R.,Genesis Cancer Care | Awad R.,Materials Hospital | Fogarty G.,Genesis Cancer Care | Fogarty G.,Materials Hospital | And 10 more authors.
Radiation Oncology | Year: 2013

Purpose: Volumetric modulated arc therapy (VMAT) can deliver intensity modulated radiotherapy (IMRT) like dose distributions in a short time; this allows the expansion of IMRT treatments to palliative situations like brain metastases (BMs). VMAT can deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) to achieve stereotactic radiotherapy (SRT) for BMs. This study is an audit of our experience in the treatment of brain metastases with VMAT in our institution.Methods and materials: Metastases were volumetrically contoured on fused diagnostic gadolinium enhanced T1 weighted MRI/planning CT images. Risk organs included hippocampus, optic nerve, optic chiasm, eye, and brain stem. The hippocampi were contoured manually as one paired organ with assistance from a neuroradiologist. WBRT and SIB were integrated into a single plan.Results: Thirty patients with 73 BMs were treated between March 2010 and February 2012 with VMAT. Mean follow up time was 3.5 months. For 26 patients, BMs arose from primary melanoma and for the remaining four patients from non-small cell lung cancer (n= 2), primary breast cancer, and sarcoma. Mean age was 60 years. The male to female ratio was 2:1. Five patients were treated without hippocampal avoidance (HA) intent. The median WBRT dose was 31 Gy with a median SIB dose for BMs of 50 Gy, given over a median of 15 fractions. Mean values for BMs were as follows: GTV = 6.9 cc, PTV = 13.3 cc, conformity index = 8.6, homogeneity index = 1.06. Mean and maximum hippocampus dose was 20.4 Gy, and 32.4 Gy, respectively, in patients treated with HA intent. Mean VMAT treatment time from beam on to beam off for one fraction was 3.43 minutes, which compared to WBRT time of 1.3 minutes. Twenty out of 25 assessable lesions at the time of analysis were controlled. Treatment was well tolerated; grade 4 toxicity was reported in one patient. The median overall survival was 9.40 months. Conclusions: VMAT for BMs is feasible, safe and associated with a similar survival times and toxicities to conventional SRT+/-WBRT. The advantage of VMAT is that WBRT and SRT can be delivered at the same time on one machine. © 2013 Awad et al.; licensee BioMed Central Ltd.


PubMed | Genesis Cancer Care
Type: Journal Article | Journal: Medical physics | Year: 2017

To demonstrate the role of continuous improvement fulfilled by the Medical Physicist in clinical 4DCT and CBCT scanning.Lung (SABR and Standard) patients 4D respiratory motion and image data were reviewed over a 3, 6 and 12 month period following commissioning testing. By identifying trends of clinically relevant parameters and respiratory motions, variables were tested with a programmable motion phantom and assessed. Patient traces were imported to a motion phantom and 4DCT and CBCT imaging were performed. Cos6 surrogate and sup-inf motion was also programmed into the phantom to simulate the long exhale of patients for image contrast tests.Patient surrogate motion amplitudes were 9.9+5.2mm (3-35) at 18+6bpm (6-30). Expiration/Inspiration time ratios of 1.4+0.5second (0.6-2.9) showed image contrast effects evident in the AveCT and 3DCBCT images. Small differences were found for patients with multiple 4DCT data sets. Patient motion assessments were simulated and verified with the phantom within 2mm. Initial image reviews to check for reconstructed artefacts and data loss identified a small number of patients with irregularities in the automatic placement of inspiration and expiration points.The Physicists involvement in the continuous improvements of a clinically commissioned technique, processes and workflows continues beyond the commissioning stage of a project. Our experience with our clinical 4DCT program shows that Physics presence is required at the clinical 4DCT scan to assist with technical aspects of the scan and also for clinical image quality assessment prior to voluming. The results of this work enabled the sharing of information from the Medical Physics group with the Radiation Oncologists and Radiation Therapists. This results in an improved awareness of clinical patient respiration variables and how they may affect 4D simulation images and also may also affect the treatment verification images.


PubMed | Genesis Cancer Care
Type: Journal Article | Journal: Medical physics | Year: 2017

To investigate the effects of external surrogate and tumour motion by observing the reconstructed phases and AveCT in an Amplitude and Time based 4DCT.Based on patient motion studies, Cos6 and sinusoidal motions were simulated as external surrogate and tumour motions in a motion phantom. The diaphragm and tumour motions may or may not display the same waveform therefore the same and different waveforms were programmed into the phantom, scanned and reconstructed based on Amplitude and Time. The AveCT and phases were investigated with these different scenarios. The AveCT phantom images were also compared with CBCT phantom images programmed with the same motions.For the same surrogate and tumour sin motions, the phases (Amplitude and Time) and AveCT indicated similar motions based on the position of the BB at the slice and displayed contrast values respectively. For cos6 motions, due to the varied time the tumour spends at each position, the Amplitude and Time based phases differed. The AveCT images represented the actual tumour motions and the Time and Amplitude based phases were represented by the surrogate with varied times.Different external surrogate and tumour motions may result in different displayed image motions when observing the AveCT and reconstructed phases. During the 4DCT, the surrogate motion is readily available for observation of the amplitude and time of the diaphragm position. Following image reconstruction, the user may need to observe the AveCT in addition to the reconstructed phases to comprehend the time weightings of the tumour motion during the scan. This may also apply to 3D CBCT images where the displayed tumour position in the images is influenced by the long duration of the CBCT. Knowledge of the tumour motion represented by the greyscale of the AveCT may also assist in CBCT treatment beam verification matching.


PubMed | Genesis Cancer Care
Type: Journal Article | Journal: Australasian physical & engineering sciences in medicine | Year: 2014

Recently individual intensity modulated radiation therapy quality assurances (IMRT QA) have been more and more performed with Gafchromic EBT series films processed in red-green-blue (R-G-B) channel due to their extremely high spatial resolution. However, the efficiency of this method is relatively low, as for each box of film, a calibration curve must be established prior to the film being used for measurement. In this study, the authors find a novel method to process the Gafchromic EBT series, that is, to use the 16-bit greyscale channel to process the exposed film rather than the conventional 48-bit R-G-B channel, which greatly increases the efficiency and even accuracy of the whole IMRT procedure. The main advantage is that when processed in greyscale channel, the Gafchromic EBT2 films exhibits a linear relationship between the net pixel value and the dose delivered. This linear relationship firstly reduces the error in calibration-curve fitting, and secondly saves the need of establishing a calibration curve for each box of films if it is only to be used for relative measurements. Clinical testing for this novel method was carried out in two radiation therapy centres that involved a total of 743 IMRT cases, and 740 cases passed the 3 mm 3 % gamma analysis criteria. The cases were also tested with small ionization chambers (cc-13) and the results were convincing. Consequently the authors recommend the use of this novel method to improve the accuracy and efficiency of individual IMRT QA procedure using Gafchromic EBT2 films.


PubMed | University of Southern Queensland, Curtin University Australia, Genesis Cancer Care and Sir Charles Gairdner Hospital
Type: | Journal: European journal of cancer care | Year: 2016

Workforce recruitment and retention are issues in radiation oncology. The working environment is likely to have an impact on retention; however, there is a lack of research in this area. The objectives of this study were to: investigate radiation therapists (RTs) and radiation oncology medical physicists (ROMPs) perceptions of work and the working environment; and determine the factors that influence the ability of RTs and ROMPs to undertake their work and how these factors affect recruitment and retention. Semi-structured interviews were conducted and thematic analysis was used. Twenty-eight RTs and 21 ROMPs participated. The overarching themes were delivering care, support in work, working conditions and lifestyle. The overarching themes were mostly consistent across both groups; however, the exemplars reflected the different roles and perspectives of RTs and ROMPs. Participants described the importance they placed on treating patients and improving their lives. Working conditions were sometimes difficult with participants reporting pressure at work, large workloads and longer hours and overtime. Insufficient staff numbers impacted on the effectiveness of staff, the working environment and intentions to stay. Staff satisfaction is likely to be improved if changes are made to the working environment. We make recommendations that may assist departments to support RTs and ROMPs.

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