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INTRODUCTION: To describe the pattern of the use of advanced radiation therapy (RT) techniques, including intensity-modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body RT (SBRT) for the management of bone metastases (BM), and the associated factors in Victoria. METHODS: We used a population-based cohort of patients from the state-wide Victorian Radiotherapy Minimum Data Set (VRMDS) who received RT for BM between 2012 and 2017. The primary outcome was proportion of RT courses using advanced RT techniques. The Cochran-Armitage test for trend was used to evaluate temporal trend in advanced RT use. Multinomial logistic regression was used to identify factors associated with advanced RT use. RESULTS: A total of 18,158 courses of RT were delivered to 10,956 patients-16,626 (91.6%) courses were 3D conformal RT, 857 (4.7%) IMRT/VMAT and 675 (3.7%) SBRT. There was a sharp increase in IMRT/VMAT use from <1% in 2012-2015, to 10.1% in 2016 and 16.3% in 2017 (P-trend < 0.001). Increase in SBRT use was more gradual, from 1.2% in 2012 to 4.8% in 2016 and 5.5% in 2017 for SBRT (P-trend<0.001). In multivariate analyses, year of RT was the strongest predictor of IMRT/VMAT use (OR = 41; 95%CI = 25-67; P < 0.001, comparing 2012-2013 and 2016-2017). Primary tumour type (prostate cancer) was the strongest predictor of SBRT use (OR = 6.07; 95% CI = 4.19-8.80; P < 0.001). CONCLUSION: Overall, there was increasing trend in the use of advanced RT techniques for BM in Victoria, with a distinct pattern for IMRT/VMAT compared with SBRT - SBRT uptake was more gradual while IMRT/VMAT uptake was abrupt, occurring contemporaneously with Medicare Benefit Scheme funding changes in 2016.

Introduction: To evaluate the pattern of use of advanced radiation therapy techniques, including intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic RT (SRT) for the management of bone metastases (BM), and the associated factors in Victoria. Method(s): We used a population-based cohort of patients from the state-wide Victorian Radiotherapy Minimum Data Set (VRMDS) who received RT for BM between 2012 and 2017. The primary outcome was: proportion of RT courses using ART. The Cochran-Armitage test for trend was used to evaluate temporal trend in ART use. Multinomial logistic regression was used to identify factors associated with ART use. Result(s): 18,158 courses of RT were delivered to 10,956 patients-16,626 (92.6%) courses were 3D conformal RT, 857 (4.7%) IMRT/ VMAT, and 675 (3.7%) SRT. There was a sharp increase in IMRT/ VMAT use from <1% in 2012-2015, to 10.1% in 2016 and 16.3% in 2017 (P-trend<0.001). Increase in SRT use was more gradual-from 1.2% in 2012 to 4.8% in 2016 and 5.5% in 2017 for SRT (Ptrend< 0.001). In multivariate analyses, year of RT was the strongest predictor of IMRT/VMAT use (OR=41; 95%CI=25-67; P<0.001, comparing 2012-2013 and 2016-2017). Other factors associated with increased likelihood of IMRT/VMAT were: cancer type (breast cancer), site of BM (pelvis), remoteness of residency (major cities), and treatment centre (private and regional). Primary tumour type (prostate cancer) was the strongest predictor of SRT use (OR=6.07; 95%CI=4.19-8.80; P<0.001). Other factors associated with increased likelihood of SRT were: younger age, site of BM (pelvis, skull, rib), higher socioeconomic status, and treatment institutions (private and metropolitan). Conclusion(s): Overall, there was increasing trend in the use of advanced RT techniques for BM in Victoria, with distinct pattern for IMRT/VMAT compared to SRT-SRT uptake was more gradual while IMRT/VMAT uptake was abrupt, occurring contemporaneously with changes in Medi

BACKGROUND: Melanoma brain metastases (MBMs) are a challenging clinical problem with high morbidity and mortality. Although first-line dabrafenib-trametinib and ipilimumab-nivolumab have similar intracranial response rates (50%-55%), central nervous system (CNS) resistance to BRAF-MEK inhibitors (BRAF-MEKi) usually occurs around 6 months, and durable responses are only seen with combination immunotherapy. We sought to investigate the utility of ipilimumab-nivolumab after MBM progression on BRAF-MEKi and identify mechanisms of resistance. METHODS: Patients who received first-line ipilimumab-nivolumab for MBMs or second/third line ipilimumab-nivolumab for intracranial metastases with BRAFV600 mutations with prior progression on BRAF-MEKi and MRI brain staging from March 1, 2015 to June 30, 2018 were included. Modified intracranial RECIST was used to assess response. Formalin-fixed paraffin-embedded samples of BRAFV600 mutant MBMs that were naïve to systemic treatment (n=18) or excised after progression on BRAF-MEKi (n=14) underwent whole transcriptome sequencing. Comparative analyses of MBMs naïve to systemic treatment versus BRAF-MEKi progression were performed. RESULTS: Twenty-five and 30 patients who received first and second/third line ipilimumab-nivolumab, were included respectively. Median sum of MBM diameters was 13 and 20.5 mm for the first and second/third line ipilimumab-nivolumab groups, respectively. Intracranial response rate was 75.0% (12/16), and median progression-free survival (PFS) was 41.6 months for first-line ipilimumab-nivolumab. Efficacy of second/third line ipilimumab-nivolumab after BRAF-MEKi progression was poor with an intracranial response rate of 4.8% (1/21) and median PFS of 1.3 months. Given the poor activity of ipilimumab-nivolumab after BRAF-MEKi MBM progression, we performed whole transcriptome sequencing to identify mechanisms of drug resistance. We identified a set of 178 differentially expressed genes (DEGs) between naïve and MBMs

The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.