Recent Australian Advances in the Radiotherapy of Skin Cancer

This paper is an expository report on some recent and current research on clinical problems in the control of skin cancer in Australia, which has a high prevalence and an increasing incidence of this disease

Volumetric modulated arc therapy is superior to conventional intensity modulated radiotherapy - a comparison among prostate cancer patients treated in an Australian centre

<p>Abstract</p> <p>Background</p> <p>Radiotherapy technology is expanding rapidly. Volumetric Modulated Arc Therapy (VMAT) technologies such as RapidArc^®(RA) may be a more efficient way of delivering intensity-modulated radiotherapy-like (IM) treatments. This study is an audit of the RA experience in an Australian department with a planning and economic comparison to IM.</p> <p>Methods</p> <p>30 consecutive prostate cancer patients treated radically with RA were analyzed. Eight RA patients treated definitively were then completely re-planned with 3D conformal radiotherapy (3D); and a conventional sliding window IM technique; and a new RA plan. The acceptable plans and their treatment times were compared and analyzed for any significant difference. Differences in staff costs of treatment were computed and analyzed.</p> <p>Results</p> <p>Thirty patients had been treated to date with eight being treated definitely to at least 74 Gy, nine post high dose brachytherapy (HDR) to 50.4Gy and 13 post prostatectomy to at least 64Gy. All radiotherapy courses were completed with no breaks. Acute rectal toxicity by the RTOG criteria was acceptable with 22 having no toxicity, seven with grade 1 and one had grade 2.</p> <p>Of the eight re-planned patients, none of the 3D (three-dimensional conformal radiotherapy) plans were acceptable based on local guidelines for dose to organs at risk. There was no statistically significant difference in planning times between IM and RA (p = 0.792). IM had significantly greater MUs per fraction (1813.9 vs 590.2 p < 0.001), total beam time per course (5.2 vs 3.1 hours, p = 0.001) and average treatment staff cost per patient radiotherapy course ($AUD489.91 vs$AUD315.66, p = 0.001). The mean saving in treatment staff cost for RA treatment was $AUD174.25 per patient.</p> <p>Conclusions</p> <p>3D was incapable of covering a modern radiotherapy volume for the radical treatment of prostate cancer. These volumes can be treated via conventional IM and RA. RA was significantly more efficient, safe and cost effective than IM. VMAT technologies are a superior way of delivering IM-like treatments.</p

Cost Analysis of Adjuvant Whole‑Brain Radiotherapy Treatment Versus No Whole‑Brain Radiotherapy After Stereotactic Radiosurgery and/or Surgery Among Adults with One to Three Melanoma Brain Metastases: Results from a Randomized Trial

Purpose We aimed to compare Australian health system costs at 12 months for adjuvant whole-brain radiotherapy (WBRT) treatment after stereotactic radiosurgery (SRS) and/or surgery versus observation among adults with one to three melanoma brain metastases. We hypothesized that treatment with adjuvant WBRT and subsequent healthcare would be more expensive than SRS/surgery alone. Methods The analysis was conducted alongside a multicentre, randomized phase III trial. A bespoke cost questionnaire was used to measure healthcare use, including hospitalizations, specialist and primary care visits, imaging, and medicines over 12 months. Mean per-patient costs were calculated based on the quantity of resources used and unit costs, reported in Australian dollars ($AU), year 2018 values. Skewness of cost data was determined using normality tests and censor-adjusted costs reported using the Kaplan–Meier sample average method. The analysis of diference in mean costs at each 2-month time point and at 12 months was performed and checked using Kruskal–Wallis, generalized linear models with gamma distribution and log link, modifed Park test, ordinary least squares, and non-parametric bootstrapping. Results In total, 89 patients with similar characteristics at baseline were included in the cost analysis (n = 43 WBRT; n = 46 observation). Hospitalization cost was the main cost, ranging from 63 to 8912-monthly cost for WBRT was$AU71,138 ± standard deviation 41,475 and for observation $AU69,848 ± 33,233; p = 0.7426. The censor-adjusted 12-monthly cost for WBRT was$AU90,277 ± 36,274 and $AU82,080 ± 34,411 for observation. There was no signifcant diference in 2-monthly costs between groups (p > 0.30 for all models). Conclusions Most costs were related to inpatient hospitalizations associated with disease recurrence. Adding WBRT after local SRS/surgery for patients with one to three melanoma brain metastases did not signifcantly increase health system costs during the frst 12 months. Trial Registration ACTRN12607000512426, prospectively registered 14 September 200

The SAMI Pilot Survey: stellar kinematics of galaxies in Abell 85, 168 and 2399

We present the SAMI Pilot Survey, consisting of integral field spectroscopy of 106 galaxies across three galaxy clusters, Abell 85, Abell 168 and Abell 2399. The galaxies were selected by absolute magnitude to have Mr < -20.25 mag. The survey, using the Sydney-AAO Multi-object Integral field spectrograph (SAMI), comprises observations of galaxies of all morphological types with 75 per cent of the sample being early-type galaxies (ETGs) and 25 per cent being late-type galaxies (LTGs). Stellar velocity and velocity dispersion maps are derived for all 106 galaxies in the sample. The lambdaR parameter, a proxy for the specific stellar angular momentum, is calculated for each galaxy in the sample. We find a trend between lambdaR and galaxy concentration such that LTGs are less concentrated higher angular momentum systems, with the fast-rotating ETGs (FRs) more concentrated and lower in angular momentum. This suggests that some dynamical processes are involved in transforming LTGs to FRs, though a significant overlap between the lambdaR distributions of these classes of galaxies implies that this is just one piece of a more complicated picture. We measure the kinematic misalignment angle, Psi, for the ETGs in the sample, to probe the intrinsic shapes of the galaxies. We find the majority of FRs (83 per cent) to be aligned, consistent with them being oblate spheroids (i.e. discs). The slow rotating ETGs (SRs), on the other hand, are significantly more likely to show kinematic misalignment (only 38 per cent are aligned). This confirms previous results that SRs are likely to be mildly triaxial systems

Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan

Background: The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness. Objective: The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. Methods: The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. Results: The resulting SAP is consistent with best practice and will allow open and transparent reporting. Conclusion: We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias

Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

<p>Abstract</p> <p>Background</p> <p>Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete.</p> <p>Methods/Design</p> <p>This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function.</p> <p>Discussion</p> <p>Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07), and the Trans Tasman Radiation Oncology Group (TROG) but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12607000512426.aspx">ACTRN12607000512426</a></p

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The SAMI Galaxy Survey: revisiting galaxy classification through high-order stellar kinematics

Recent cosmological hydrodynamical simulations suggest that integral field spectroscopy can connect the high-order stellar kinematic moments h3 (~skewness) and h4 (~kurtosis) in galaxies to their cosmological assembly history. Here, we assess these results by measuring the stellar kinematics on a sample of 315 galaxies, without a morphological selection, using two-dimensional integral field data from the SAMI Galaxy Survey. Proxies for the spin parameter (${\lambda }_{{R}_{{\rm{e}}}}$) and ellipticity (${\epsilon }_{{\rm{e}}}$) are used to separate fast and slow rotators; there exists a good correspondence to regular and non-regular rotators, respectively, as also seen in earlier studies. We confirm that regular rotators show a strong h3 versus $V/\sigma$ anti-correlation, whereas quasi-regular and non-regular rotators show a more vertical relation in h3 and $V/\sigma$. Motivated by recent cosmological simulations, we develop an alternative approach to kinematically classify galaxies from their individual h3 versus $V/\sigma$ signatures. Within the SAMI Galaxy Survey, we identify five classes of high-order stellar kinematic signatures using Gaussian mixture models. Class 1 corresponds to slow rotators, whereas Classes 2–5 correspond to fast rotators. We find that galaxies with similar {\lambda }_{{R}_{{\rm{e}}}}\mbox{--}{\epsilon }_{{\rm{e}}} values can show distinctly different {h}_{3}\mbox{--}V/\sigma signatures. Class 5 objects are previously unidentified fast rotators that show a weak h3 versus $V/\sigma$ anti-correlation. From simulations, these objects are predicted to be disk-less galaxies formed by gas-poor mergers. From morphological examination, however, there is evidence for large stellar disks. Instead, Class 5 objects are more likely disturbed galaxies, have counter-rotating bulges, or bars in edge-on galaxies. Finally, we interpret the strong anti-correlation in h3 versus $V/\sigma$ as evidence for disks in most fast rotators, suggesting a dearth of gas-poor mergers among fast rotators

The SAMI Galaxy Survey: Cubism and covariance, putting round pegs into square holes

We present a methodology for the regularization and combination of sparse sampled and irregularly gridded observations from fibre-optic multiobject integral field spectroscopy. The approach minimizes interpolation and retains image resolution on combining subpixel dithered data. We discuss the methodology in the context of the Sydney-AAO multiobject integral field spectrograph (SAMI) Galaxy Survey underway at the Anglo-Australian Telescope. The SAMI instrument uses 13 fibre bundles to perform high-multiplex integral field spectroscopy across a 1° diameter field of view. The SAMI Galaxy Survey is targeting ~3000 galaxies drawn from the full range of galaxy environments. We demonstrate the subcritical sampling of the seeing and incomplete fill factor for the integral field bundles results in only a 10 per cent degradation in the final image resolution recovered. We also implement a new methodology for tracking covariance between elements of the resulting data cubes which retains 90 per cent of the covariance information while incurring only a modest increase in the survey data volume