[18F]-fluoroethyl-L-tyrosine (FET) in glioblastoma (FIG) TROG 18.06 study: protocol for a prospective, multicentre PET/CT trial.

INTRODUCTION: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication. METHODS AND ANALYSIS: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival. ETHICS AND DISSEMINATION: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12619001735145.

High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes.

INTRODUCTION: To examine the long-term outcomes of high dose rate brachytherapy boost (HDR-BT) combined with external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer patients. METHODS: Data from 95 patients who underwent combined EBRT (50.4 Gy) and HDR-BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method. Regression analysis was conducted to identify important predictors of outcomes. RESULTS: A total of 24 patients received an initial HDR-BT dose of 18 Gy in three fractions, with the remaining 71 patients receiving 16 Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow-up was 58 months. The 5-year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P > 0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%. CONCLUSION: The combined HDR-BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre-emptive TURP and/or HS insertion.

Fiducial markers: can the urologist do better?

INTRODUCTION: Radiotherapy to the bladder has a risk of toxicity to pelvic structures, which can be reduced by using fiducial markers for targeting. Injectable contrast offers an alternative marker to gold seeds, which may fall out or exacerbate scarring. Combining contrast agents with tissue glue can minimize dispersion through tissue, enhancing its utility. We evaluated combinations of contrast agents and tissue glue using porcine bladder, for feasibility and utility as fiducial markers to aid image-guided radiotherapy. METHODS: Different contrast agents (Lipiodol ultra or Urografin) were combined with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were endoscopically injected into porcine bladder submucosa to identify the area of interest with multiple fiducial markers. The porcine bladders were imaged within a phantom porcine pelvis using standard radiation therapy imaging modalities. The feasibility as an injectable fiducial marker and visibility of each fiducial marker on imaging were scored as binary outcomes by two proceduralists and two radiation therapists, respectively. RESULTS: Lipiodol-glue combinations were successfully administered as multiple fiducials that were evident on CT and CBCT. Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol Glubran2 combination was deemed subjectively easiest to use at delivery, and a better fiducial on KV imaging. CONCLUSION: This study demonstrates the feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue glue, which, injected endoscopically, provides discrete and visible fiducial markers to aid image-guided radiotherapy. Although promising, further study is required to assess the durability of these markers through a course of radiotherapy.

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.