Patterns of the use of advanced radiation therapy techniques for the management of bone metastases and the associated factors in Victoria.

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

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.</p

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events

Stereotactic Body Radiation Therapy for Spinal Metastases: Benefits and Limitations

Progress in biological cancer characterization, targeted systemic therapies and multimodality treatment strategies have shifted the goals of radiotherapy for spinal metastases from short-term palliation to long-term symptom control and prevention of compilations. This article gives an overview of the spine stereotactic body radiotherapy (SBRT) methodology and clinical results of SBRT in cancer patients with painful vertebral metastases, metastatic spinal cord compression, oligometastatic disease and in a reirradiation situation. Outcomes after dose-intensified SBRT are compared with results of conventional radiotherapy and patient selection criteria will be discussed. Though rates of severe toxicity after spinal SBRT are low, strategies to minimize the risk of vertebral compression fracture, radiation induced myelopathy, plexopathy and myositis are summarized, to optimize the use of SBRT in multidisciplinary management of vertebral metastases

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer

OBJECTIVE: To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. PATIENTS AND METHODS: This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. RESULTS: A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease. Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa (84%) were more likely to have ADT than men with favourable NCCN intermediate-risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men treated in public institutions (66%, vs 47% in private institutions; P < 0.001) and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were more likely to receive ADT. There was a trend towards an increase in ADT utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses (adjusting for age, tumour-related factors, year of treatment and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3; P = 0.002), more likely to receive ADT with RT, respectively, while men with high-risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7-5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive ADT with RT, respectively. CONCLUSION: This is the largest Australasian contemporary series reporting on the pattern of use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions

Androgen deprivation therapy use with post-prostatectomy radiotherapy in the Prostate Cancer Outcomes Registry Victoria

INTRODUCTION: The aim of this study is to evaluate the use of androgen deprivation therapy (ADT) with post-prostatectomy radiotherapy (PPRT) in a population-based cohort of Australian men. METHODS: This is a prospective cohort of men with localised prostate cancer captured in the Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who received PPRT between January 2010 and December 2015. The primary outcome was ADT use with PPRT. Multivariate logistic regressions were used to identify patient, tumour and institutional factors influencing ADT use. RESULTS: 485 men were included in this study - 115 (24%) had pT2 disease, 231 (48%) pT3a, 134 (28%) pT3b and 5 (1%) pT4. Eighteen (4%) men had ISUP grade 1 disease, 139 (29%) ISUP grade 2, 170 (35%) ISUP grade 3 and 158 (33%) ISUP grade 4/5, while 267 (64%) men had positive surgical margins. Median time from prostatectomy to PPRT was 8.1 months (IQR = 5.3-13.9). Sixty-six (14%) patients had ADT with PPRT. In multivariate analyses, men who had increased age (OR = 1.06; 95% CI = 1.01-1.11), seminal vesicle involvement (OR = 3.81; 95% CI = 1.63-8.91) and underwent treatment in regional centres (OR = 2.17; 95% CI = 1.08-4.33) were more likely to have ADT with PPRT. CONCLUSION: We reported that 14% of men treated with PPRT received ADT in a population-based cohort of Australian men, which was less than half of the proportion of ADT use with PPRT in the US. It will be of interest to evaluate the uptake of ADT with PPRT in the coming years following recent publications of level 1 evidence confirming overall survival benefits of ADT with PPRT

Stereotactic Body Radiation Therapy for Spine Metastases—Findings from an Australian Population-Based Study

Peer reviewed: TrueBackground: To evaluate the use of stereotactic body radiation therapy (SBRT) for spine metastases and the associated factors in Australia. Methods: The Victorian Radiotherapy Minimum Dataset, which captures all episodes of radiotherapy delivered in the state of Victoria, was accessed to evaluate the patterns and trends of SBRT for spine metastases. The primary outcome was SBRT use and associated factors. Results: There were 6244 patients who received 8861 courses of radiotherapy for spine metastases between 2012 and 2017. Of these, 277 (3%) courses were SBRT, which increased from 0.4% in 2012 to 5% in 2017 (P-trend < 0.001). There was a higher proportion of SBRT use in patients with prostate cancer (6%) and melanoma (4%) compared to other cancers (2–3%) (p < 0.001). Patients from the highest socioeconomic quintiles (5%) were more likely to be treated with SBRT compared to patients from the lowest socioeconomic quintiles (3%) (p < 0.001). There was a higher proportion of SBRT use in private radiotherapy centres (6%) compared to public radiotherapy centres (1%) (p < 0.001). No spine SBRT was delivered in regional centres. In multivariate analyses, the year of treatment, age, primary cancers and radiotherapy centres were independently associated with SBRT use. Conclusion: This is the first Australian population-based study quantifying the increasing use of spine SBRT; however, the overall use of spine SBRT remains low. We anticipate an ongoing increase in spine SBRT, as spine SBRT gradually becomes the standard-of-care treatment for painful spine metastases

Contemporary practice patterns of stereotactic radiosurgery for brain metastasis:A review of published Australian literature

There has been a shift in the management of brain metastasis (BM), with increasing use of stereotactic radiosurgery (SRS) and delaying/avoiding whole-brain radiotherapy (WBRT), given the concern regarding the long-term neurocognitive effect and quality of life impact of WBRT. It is, however, unclear as to the contemporary practice pattern and outcomes of SRS in Australia. We conducted a literature search in PubMed and MEDLINE using a series of keywords: 'stereotactic', 'radiosurgery' and 'brain metastases', limiting to Australian studies, which report on clinical outcomes following SRS. Eight studies - one randomized trial and seven retrospective cohort studies - were identified and included in this review. A total of 856 patients were included, with the most common primary tumour types being melanoma, lung cancer and breast cancer. Approximately half of the patients had solitary BM, while 7% had 10 or more BM lesions. SRS is not routinely given in combination with WBRT. The 6-month intracranial control and 1-year intracranial control following SRS were reported in the range of 67-87% and 48-82%, respectively, whereas the 1-year overall survival and 2-year overall survival were reported in the range of 37-60% and 20-36%, respectively. There are limited data reported on SRS-related toxicities in all included studies. Overall, despite increasing use of SRS for BM, there is a low number of published Australian series in the literature. There is a potential role for establishing an Australian clinical quality registry or collaborative consortium for SRS in BM, to allow for systematic prospective data collection, and benchmarking of quality and outcomes of SRS