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

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

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

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 2D integral field data from the SAMI Galaxy Survey. A proxy for the spin parameter ($\lambda_{R_e}$) and ellipticity ($\epsilon_e$) 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. 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 $\lambda_{R_e}-\epsilon_e$ values can show distinctly different h3-$V/\sigma$ signatures. Class 5 objects are previously unidentified fast rotators that show a weak h3 versus $V/\sigma$ anti-correlation. 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.Comment: Accepted for Publication in The Astrophysical Journal. 35 pages and 30 figures, abstract abridged for arXiv submission. The key figures of the paper are: 7, 11, 12 , and 1

Cutaneous squamous cell carcinoma metastatic to parotid - analysis of prognostic factors and treatment outcome

Abstract Background Cutaneous squamous cell carcinoma (cSCC) comprises 20% of all skin cancer of the head and neck. A minority will metastasize to regional parotid lymph nodes. This study evaluates the St Vincent’s Hospital, Sydney experience between 1996 and 2006. Methods A retrospective review was performed of patients who were evaluated in our multidisciplinary head and neck clinic with metastatic cSCC to parotid, and all treatment and pathologic details were reviewed. Statistical analysis, including univariate and multivariate analyses, were performed using Cox proportional hazards regression mode, overall and disease-specific survival were estimated by the Kaplan-Meier method. Results Sixty-seven patients were identified. Some 90 % were male, and with a mean age of 72.8 years. One died on the first postoperative day. The remaining 66 patients received radiotherapy. For these 66 patients, the two-year and five-year overall survival rate was 0.83 and 0.72, respectively. The two-year and five-year disease-free survival rate was 0.91 and 0.83 respectively. Overall survival was only significantly correlated to the extent of parotidectomy (superficial versus total; P = 0.0256). Margin status was available in 59 patients. The only parameter that significantly correlated with disease-free survival was margin status (close/negative versus positive P = 0.0348). Other parameters of immune suppression, perineural invasion, extra capsular extension, degree of tumour differentiation, number of positive nodes, extent of neck dissection and radiotherapy dosage delivered did not confer prognostic significance. Conclusions This study confirmed the association of adverse prognostic implication of positive margins on disease-free survival. Immune compromise was not a significant factor in this small group. Further studies are warranted in this population.</p