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To report on the usability, safety, symmetry, and effectiveness of hyaluronic acid (HA) injected between the prostate and the rectum for patients undergoing treatment for prostate cancer with external beam radiotherapy (EBRT), and present a novel definition of rectal spacer symmetry that is reproducible and independent of patient anatomy.102 consecutive patients with clinical stage of T1c-3b prostate cancer underwent general anaesthesia for fiducial marker insertion and injection of HA into the perirectal space before EBRT. HA safety, symmetry, separation, and usability based on user experience were assessed.HA insertion was completed with a 100% success rate independent of user experience, rated as 'easy' or 'very easy' in all cases. There were no postoperative complications reported. The mean (SD) recto-prostatic separation for all patients at the base, midgland and apex were 12 (±2) mm, 11 (±2) mm, and 9 (±1) mm respectively. The mean sagittal length of the implant was 43 (±5) mm. The implant was rated as symmetrical in 98% of cases. The mean rV70Gy was 1.6% (IQR 0.8-3.3%) for patients receiving 78-80Gy. The mean rV53Gy was 2.8% (IQR 1.2-4.8%) for patients receiving 60-62Gy. The median prostate size was 43.5 cc (IQR 32-57).Injection of HA was able to achieve highly symmetrical recto-prostatic separation, with new users able to produce excellent separation, particularly at the apex, achieving similar dosimetry outcomes as competent and experienced users. HA is safe, easy to use, and significantly reduced mean rV70Gy and rV53Gy compared to non-spacer patients.

Supplementary Table S1 from Pretreatment Transcriptional Profiling for Predicting Response to Neoadjuvant Chemoradiotherapy in Rectal Adenocarcinoma

Purpose: Patients presenting with locally advanced rectal cancer currently receive preoperative radiotherapy with or without chemotherapy. Although pathologic complete response is achieved for approximately 10% to 30% of patients, a proportion of patients derive no benefit from this therapy while being exposed to toxic side effects of treatment. Therefore, there is a strong need to identify patients who are unlikely to benefit from neoadjuvant therapy to help direct them toward alternate and ultimately more successful treatment options.Experimental Design: In this study, we obtained expression profiles from pretreatment biopsies for 51 rectal cancer patients. All patients underwent preoperative chemoradiotherapy, followed by resection of the tumor 6 to 8 weeks posttreatment. Gene expression and response to treatment were correlated, and a supervised learning algorithm was used to generate an original predictive classifier and validate previously published classifiers.Results: Novel predictive classifiers based on Mandard's tumor regression grade, metabolic response, TNM (tumor node metastasis) downstaging, and normal tissue expression profiles were generated. Because there were only 7 patients who had minimal treatment response (>80% residual tumor), expression profiles were used to predict good tumor response and outcome. These classifiers peaked at 82% sensitivity and 89% specificity; however, classifiers with the highest sensitivity had poor specificity, and vice versa. Validation of predictive classifiers from previously published reports was attempted using this cohort; however, sensitivity and specificity ranged from 21% to 70%.Conclusions: These results show that the clinical utility of microarrays in predictive medicine is not yet within reach for rectal cancer and alternatives to microarrays should be considered for predictive studies in rectal adenocarcinoma. Clin Cancer Res; 17(9); 3039–47. ©2011 AACR.

Introduction Guidelines recommend that the proximal seminal vesicles (PrSV) should be included in the clinical target volume for locally advanced prostate cancer patients undergoing radiotherapy. Verification and margins for the prostate may not necessarily account for PrSV displacement. The purpose was to determine the inter‐fraction displacement of the PrSV relative to the prostate during radiotherapy. Methods Fiducials were inserted into the prostate, and right and left PrSV (RSV and LSV) in 30 prostate cancer patients. Correctional shifts for the prostate, right and left PrSV and pelvic bones were determined from each patient's 39 daily orthogonal portal images relative to reference digitally reconstructed radiographs. Results There was a significant displacement of the RSV relative to the prostate in all directions: on average 0.38 mm (95% confidence interval (CI) 0.26 to 0.50) to the left, 0.80–0.81 mm (CI 0.68 to 0.93) superiorly and 1.51 mm (CI 1.36 to 1.65) posteriorly. The LSV was significantly displaced superiorly to the prostate 1.09–1.13 mm (CI 0.97 to 1.25) and posteriorly 1.81 mm (CI 1.67 to 1.96), but not laterally (mean 0.06, CI −0.06 to 0.18). The calculated PTV margins (left–right, superior–inferior, posterior–anterior) were 4.9, 5.3–5.6 and 4.8 mm for the prostate, 5.2, 7.1–8.0 and 9.7 mm for the RSV, and 7.2, 7.5–7.6 and 8.6 mm for the LSV. Conclusion There is a significant displacement of the PrSV relative to the prostate during radiotherapy. Greater margins are recommended for the PrSV compared to the prostate., Seminal vesicles displacement is greater than that of the prostate during radiotherapy and requires a greater margin.

Prostate cancer (PCa) is a multifaceted, heterogeneous disease (with 7 molecular subtypes), which can metastasize to common sites, such as bone, lymph nodes, liver, and lungs. However, with PSMA PET imaging, rare sites of metastasis are increasingly discovered. We report 5 cases of unusual metastases in patients with castrate-sensitive PCa: solitary right inguinal nodal metastasis, solitary abdominal wall metastasis, penile shaft metastases, solitary perineum metastasis, and pleural metastases. These cases further support the use of PSMA-PET imaging in PCa monitoring, with the ability to detect solitary, small volume, and rare sites of metastases, which may not be apparent on conventional imaging.

Prostate cancer is the most commonly diagnosed cancer among Australian men. Current whole gland radiotherapy treatment regimens are associated with known toxicities. The MR-Linac has the capability to deliver real-time visually guided radiation to enable focal therapy and reduce toxicity through decreasing radiation doses to organs at risk. This review article discusses the rationale, potential benefits and limitations of the MR-Linac in focal prostate stereotactic body radiotherapy (SBRT), in an effort to reduce toxicity-related side effects for men with low to favourable-intermediate risk prostate cancer. Pubmed was systemically for all published and ongoing trials using the search terms ‘Prostate’ and ‘MRI Linac or MR Linac’. 8 articles were reviewed, of those 1 was deemed relevant, additions were made and expert opinions in the field were sought regarding the most relevant research. Real-time MRI imaging during the delivery of each fraction with daily plan adaption is now a reality due to the development of the MR-Linac system. It is hoped that with improved real-time imaging, treatment accuracy can be improved, increasing the percentage of the planning target volume receiving the prescribed dose while reducing radiation to the surrounding organs at risk. Early results of prostate SBRT are promising but further research is needed into long term survival benefits and toxicity related outcomes. Focal stereotactic radiotherapy for low-risk intermediate prostate cancer using the MR-Linac has the potential to provide adequate tumour control while decreasing the toxicity and quality of life impact of whole gland treatment for men with localised prostate cancer.

Objective To review the utility of vesicourethral anastomosis (VUA)-directed biopsy in the setting of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa) in patients who have undergone evaluation by gallium-68 prostate-specific membrane antigen positron emission tomography with computed tomography (68 Ga-PSMA PET/CT). Methods We completed a retrospective review of a prospectively maintained dataset from January 2015 to August 2020. Patient demographics were recorded for those who experienced BCR, as defined by a rise in prostate-specific antigen (PSA) level to above 0.2 ng/mL, who had a 68 Ga-PSMA PET/CT that did not demonstrate recurrence within the prostate bed, and who subsequently underwent a transperineal ultrasonography (TPUS)-guided biopsy directed at the VUA. Histological reporting of the biopsies was undertaken in order to determine whether the benefits of salvage radiation therapy (SRT) could be justified by the presence of cancer cells. Results Eighteen patients who had a 68 Ga-PSMA PET/CT and underwent VUA-directed biopsy were identified as having BCR. 68 Ga-PSMA PET/CT scans demonstrated avidity at the VUA in none of the patients, although two out of 18 patients showed avidity in the seminal vesicles and two out of 18 patients showed avidity within regional lymph nodes. Histology from the TPUS-guided, VUA-directed biopsies demonstrated no prostatic tissue in six out of 18 and presence of prostatic tissue in 12 out of 18 of patients, respectively. In 7 out of 18 cases, there was histological evidence of recurrent PCa at the VUA in the absence of a positive 68 Ga-PSMA PET/CT scan. Conclusion This study highlights the potential value of VUA-directed biopsy. We are reminded that a negative 68 Ga-PSMA PET/CT does not exclude local recurrence and that the addition of a VUA-directed biopsy may aid in the decision-making process for patients with BCR following RP, especially when 68 Ga-PSMA PET/CT is locally negative. When the result of both 68 Ga-PSMA PET/CT and VUA-directed biopsy are negative, it should encourage clinicians to share decision-making in regard to undertaking SRT vs continuing BCR surveillance. This may delay the possible side effects associated with SRT, despite its excellent PSA failure-free survival rate.

Purpose Clinician inexperience, intra–observer and inter–observer variations in tumour definition may affect staging, radiotherapy target definition, and treatment outcomes, particularly in rare cancers. The purpose of this study was to assess the correlation between semi–automated methods of primary anal cancer (AC) definition and our current clinical standard of manual clinician definition using 18F–FDG–PET imaging and to provide recommendations for clinical use. Methods All patients referred for chemoradiotherapy for AC between 2012 and 2016 were prospectively enrolled, with all 18F–FDG–PET imaging acquired within one year of chemoradiotherapy collected. Three methods of primary AC definition were performed on all PET datasets. Manual definition by an experienced radiologist was considered the clinical standard for comparison of volume and coincidence (Dice coefficient) in our study. Semi–automated techniques assessed included a gradient–based SUV (SUV–gradient) method and a SUV threshold method with a range of thresholds relative to SUVmax (40 (T40), 50 (T50) and 60% (T60)). Results Ten patients were enrolled with 33 PET study sets available for analysis. While all methods created contours on pre– and post–treatment scans, manual definition of PET–avid disease was only necessary on 11 of the 33 study sets. SUV–gradient and T40 defined contours were not statistically different in volume to the clinical standard (p = 0.83 & 0.72 respectively). The observed Dice coefficient relative to the manual clinician contours were 0.75 and 0.73 for the SUV–gradient and T40 methods respectively. Conclusions It is possible to define gross AC using SUV–based methods, with the SUV–gradient–based method followed by the T40 method most closely correlating with our current clinical standard. The SUV–gradient–based method studied is housed within a proprietary clinical system. A semi–automated approach that uses a vendor neutral T40 method and the clinician’s knowledge and skill appears optimal in defining AC. With this approach AC may be defined reliably to enhance efficiencies in radiotherapy and nuclear medicine processes, and to support clinicians in identifying and defining this rare disease. Trial registration ANZCTR, ACTRN12620000066987. Registered 28 January 2020–Retrospectively registered, https://www.anzctr.org.au/ACTRN12620000066987.aspx

Highlights • Novel liquid glue fiducials consisting of a radiographic contrast agent and tissue glue. • The first demonstration of visible liquid ethiodized oil tissue glue fiducials being delivered into a fluid-filled bladder. • Ex vivo Pigs bladder and Pig pelvis to demonstrate the deliverability of visible discrete fiducials into a fluid-filled bladder. • Utilization of clinical tools to analyze CT number voxel histograms to characterize the glue fiducials and artifact and compare them to gold fiducial markers in a 3-dimensional manner. • Ethiodized oil glue fiducials have online visualization qualities comparable to gold fiducials without the associated metal related artifact., Background and purpose Image-guidance with fiducials has been shown to improve pelvic radiotherapy outcome. However, bladder fiducials using ethiodized oil (EO) alone can disperse widely, and gold causes Computed Tomography scan (CT) metal artifacts. The study's purpose was to investigate the ability to deliver EO-tissue glue fiducials and compare them to gold for bladder radiotherapy image guidance. Materials and methods A fluid-filled porcine bladder model was used to assess the ability to cystoscopically inject visible EO glue fiducials into the submucosa. We then transferred the bladders into a porcine pelvis for imaging and compared them to gold fiducials using CT, Cone Beam CT (CBCT), and kilovoltage (KV) planar views. A tissue-equivalent phantom was utilized to analyze the CT number Hounsfield Unit (HU) characteristics and artifacts of the glue and gold fiducials. Percentile ranges and normal tissue voxel percentages of the subsequent CT number voxel histogram from a 2 cm sphere surrounding the fiducial was used to characterize the artifact. Results We successfully delivered all EO glue fiducials into the porcine bladders as discrete fiducials. They were well seen on CT, CBCT, and KV imaging. The glue fiducials had lower CT number values, but less CT number spread of the voxel percentile ranges consistent with the diminished contrast and less artifact than gold. The glue fiducial types had similar CT number characteristics. Conclusion This study has shown that EO glue fiducials can be delivered with online visualization qualities comparable to gold fiducials without metal-related artifacts.

Highlights • Understanding feeding tube risk is critical to optimal weight maintenance during radiotherapy. • T-stage, Level II lymphadenopathy risk stratify feeding tube use into 4 groups. • The addition of cervical oesophagus dose can further refine these risk stratified groups., Introduction To identify organs to which dose limitation using intensity modulated radiotherapy (IMRT) can potentially modify the incidence and duration of feeding tube use, during and immediately following therapy for head and neck cancer. Materials and methods One hundred and fourteen patients treated with definitive IMRT (± concurrent chemotherapy) head and neck mucosal cancers were included. Patients received a prophylactic feeding tube and followed up by a dietician for at least eight weeks post-radiotherapy. Salivary and swallowing organs were delineated for each patient. Tumour and dosimetric variables were recorded for all patients and analysed for incidence and duration of feeding tube use for at least 25% of dietary requirements. Results Multivariate analysis showed T-classification ≥3 and level II lymphadenopathy as independent significant predictors of incidence and duration of feeding tube use in oral cavity, pharyngeal and supraglottic primaries. Mean dose deposited in the cervical oesophagus over 36Gy further increased the incidence and duration of feeding tube use. Mean dose deposited in the base of tongue and superior pharyngeal constrictor muscles affected incidence and duration of feeding tube use, respectively. Discussion In patients treated with definitive IMRT, T-classification and Level II lymphadenopathy, combined with a mean cervical oesophagus dose over 36Gy can a stratify patients into eight distinct risk groups for using feeding tubes for at least 25% of their dietary requirements.

Stereotactic body radiotherapy has emerged as one of the preferred treatments for patients with spine metastases, with the potential for long-term control from lesion irradiation. Post-treatment vertebral compression fractures are a known complication of this therapy, contributing to worsening pain and reduced quality of life, sometimes requiring surgical intervention. This review explores the current knowledge of post-radiotherapy fractures, in terms of the rates and associated predictive factors. A search of databases including Medline, Embase and the Cochrane Library was conducted using keywords such as 'vertebral compression fracture', 'stereotactic body radiotherapy' and 'spine metastases'. The search was limited to published studies up to March 2019, reporting clinical outcomes including both the post-treatment fracture rate and statistical identification of associated risk factors. Rates of post-treatment fractures ranged from 4 to 39%. A variety of factors were found to increase the risk, including the appearance of lytic vertebral disease, degree of pre-existing compression, spinal malalignment, increased dose per fraction and a Spinal Instability Neoplastic Score >6. This knowledge can enable clinicians to counsel patients when considering management options for spine metastases, maintaining the balance between local tumour control and the risk of subsequent fracture.

BACKGROUND Image-guided radiotherapy (IGRT) has significantly improved the precision in which radiotherapy is delivered in cancer treatment. Typically, IGRT uses bony landmarks and key anatomical structures to locate the tumor. Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue. The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied. However, placement requires expertise and specialized endoscopic ultrasound equipment. This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT. AIM To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients. METHODS A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne, Australia was conducted. Up to four liquid fiducials were inserted per patient, each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil (Lipiodol; Aspen Pharmacare) and n-butyl 2-cyanoacrylate (Histoacryl®; B. Braun). A 23-gauge injector (Cook Medical) was used for the injection. All procedures were performed by or under the supervision of a gastroenterologist. Liquid fiducial-based IGRT (LF-IGRT) consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy. Patients received standard-IGRT (S-IGRT) if fiducial visibility was insufficient, consisting of bone match as a surrogate for tumor position. Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments. RESULTS 52 patients were referred for liquid fiducial placement within the study period. A total of 51 patients underwent liquid fiducial implantation. Of these a total of 31 patients received radiotherapy. Among these, the median age was 77.4 years with a range between 57.5 and 88.8, and 64.5% were male. Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT. There were no complications after endoscopic implantation of liquid fiducials in our cohort. The cohort overall survival (OS) post-radiotherapy was 19 mo (range 0 to 87 mo). Whilst the progression-free survival (PFS) post-radiotherapy was 13 mo (range 0 to 74 mo). For those treated with curative intent, the median OS was 22.0 mo (range 0 to 87 mo) with a PFS median of 14.0 mo (range 0 to 74 mo). Grade 3 complication rate post-radiotherapy was 29%. CONCLUSION LF-IGRT is feasible in 87.1% of patients undergoing liquid fiducial placement through standard gastroscopy injection technique. Our cohort has an overall survival of 19 mo and PFS of 13 mo. Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.

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.

Purpose The aim of this retrospective study was to investigate the use of a radiopaque tissue fiducial marker (TFM) in the treatment of prostate cancer patients who undergo post-prostatectomy radiotherapy (PPRT). TFM safety, its role and benefit in quantifying the set-up uncertainties in patients undergoing PPRT image-guided radiotherapy were assessed. Materials and methods A total of 45 consecutive PPRT patients underwent transperineal implantation of TFM at the level of vesicourethral anastomosis in the retrovesical tissue prior to intensity-modulated radiotherapy. Prostate bed motion was calculated by measuring the position of the TFM relative to the pelvic bony anatomy on daily cone-beam computed tomography. The stability and visibility of the TFM were assessed in the initial 10 patients. Results No postoperative complications were recorded. A total of 3,500 images were analysed. The calculated prostate bed motion for bony landmark matching relative to TFM were 2.25 mm in the left-right, 5.89 mm in the superior-inferior, and 6.59 mm in the anterior-posterior directions. A significant 36% reduction in the mean volume of rectum receiving 70 Gy (rV70) was achieved for a uniform planning target volume (PTV) margin of 7 mm compared with the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recommended PTV margin of 10 mm. Conclusion The use of TFM was safe and can potentially eliminate set-up errors associated with bony landmark matching, thereby allowing for tighter PTV margins and a consequent favourable reduction in dose delivered to the bladder and rectum, with potential improvements in toxicities.

Purpose To report on rectal dosimetric and toxicity outcomes of intermediate and high-risk prostate cancer patients undergoing combined high-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) with or without hydrogel spacer (HS) insertion. Material and methods A total of 97 patients were analyzed in this study, with 32 patients (33%) who had HS insertion compared with a preceding group of 65 patients (67%) without HS. HS safety, the dosimetric effects on organs at risk (rectal, urethral, penile bulb, and bladder) as well as gastrointestinal (GI) and genitourinary toxicity were evaluated and compared between the two groups. Results The median prostate-rectal separation achieved with HS was 10 mm (range, 5-14 mm). There were no post-operative complications following HS insertion. Patients with HS had significantly lower radiation dose to the rectum across all rectal dose volumes from rV30 to rV80, whether in absolute volume (cc) or as percentage of contoured OAR (p < 0.001). There was also significantly less acute > grade 1 GI toxicity (12.5% vs. 30.8%, p = 0.05) and a trend towards less late grade 1 GI toxicity (0% vs. 7.7%; p = 0.11) in the HS group compared to the non-HS group. Conclusions Insertion of HS in prostate cancer patients receiving combined HDR and EBRT is safe and has resulted in a significant radiation dose reduction to the rectum, resulting in significantly less acute GI toxicity and a trend towards less late GI toxicity.

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm3 [−2.0 to 15.4], p = 0.21) and tibia (1.9 mg HA/cm3 [−3.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12 months (17.3 mgHA/cm3 [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10 g/cm2 [0.07 to 0.13]), p

The purpose of this study was to investigate whether the metabolic tumor volume (MTV) of head and neck primary tumors may be a significant prognostic factor for feeding tube (FT) use and FT dependence. Seventy-nine patients with evaluable primary tumors, pre-therapy FDG-PET scans, treated with definitive intensity-modulated radiotherapy (IMRT) (± concurrent chemotherapy) for head and neck mucosal cancers were included. MTV was quantified and recorded for the primary lesion using a minimum standardized uptake value (SUV) threshold of 2.0. Patients were recommended prophylactic FT and followed up by a dietician for at least eight weeks of post-radiotherapy. Associations between MTV, dose to swallowing organs at risk, FT use, and FT dependence were analyzed. MTV was positively correlated with gross tumor volume (GTV) (r = 0.7357; p

The purpose of this study was to determine whether the degree of prostate to rectal separation using a hydrogel spacer (HS) and its effect on decreasing rectal dose can be reproduced in the community setting. Thirty one patients with cT1-3aN0M0 prostate adenocarcinoma receiving radical radiotherapy to 78 Gy were recruited to the study. The primary endpoint was the proportion of patients achieving at least 25% reduction in volume of rectum receiving 70 Gy (rV70). Other endpoints included degree of prostate to rectum separation, HS insertion-related adverse events and the proportion of patients with grade 1 or worse acute or late gastrointestinal (GI) and genitourinary (GU) toxicity. All patients had successful insertion of their HS with no peri-operative toxicity. The mean prostate–rectal separation achieved was 10.5 mm. Twenty nine (93.5%) patients achieved a reduction in rV70 of at least 25%. Acute grade 1 GI toxicity was reported in 3 patients. All symptoms had resolved by 3 months post RT. Late grade 1 GI toxicity was reported in one patient (3.2%) with bowel frequency occurring at 6 months and resolving by 12 months post RT. There was no grade 2 or 3 acute or late GI toxicity seen. In conclusion, this study illustrates that the application and benefits of HS on reducing GI rectal dose endpoints and toxicities during prostate cancer RT can be reliably replicated in a community setting similar to centres participating in the randomised trial under high quality assurance trial monitoring.

Objective To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). Patients and methods In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. Results There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. Conclusion Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

Purpose To report the 5-year biochemical relapse-free survival (BRFS), overall survival (OS), and long-term toxicity outcomes of patients treated with low-dose-rate (LDR) brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Material and methods Between 2004 and 2011, 371 patients were treated with LDR brachytherapy as monotherapy. Of these, 102 patients (27%) underwent transurethral resection of the prostate (TURP) prior to implantation. Follow-up was performed every 3 months for 12 months, then every 6 months over 4 years and included prostate specific antigen evaluation. The biochemical relapse-free survival (BRFS) was defined according to the Phoenix criteria. Acute and late toxicities were documented using the Common Terminology Criteria for Adverse Events version 4.0. The BRFS and OS estimates were calculated using Kaplan-Meier plots. Univariate and multivariate analyses were performed to evaluate outcomes by pre-treatment clinical prognostic factors and radiation dosimetry. Results The median follow-up of all patients was 5.45 years. The 5-year BRFS and OS rates were 95% and 96%, respectively. The BRFS rates for patients with Gleason score (GS) > 7 and GS ≤ 6 were 96% and 91% respectively (p = 0.06). On univariate analysis, T1 and T2 staging, risk-group classification, and prostate volumes had no impact on survival at 5 years (p > 0.1). Late grade 2 and 3 genitourinary (GU) toxicities were observed in 10% and 5% of patients respectively. Additionally, patients with prior TURP had a greater incidence of late grade 2 or 3 urinary retention (p = 0.001). There were 14 deaths in total; however, none were attributed to prostate cancer. Conclusions LDR brachytherapy is an effective treatment option in low- to intermediate-risk prostate cancer patients. We observed low biochemical relapse rates and minimal GU toxicities several years after treatment in patients with or without TURP. However, a small risk of urinary retention was observed in some patients.

Background: Vesico-urethral anastomosis (VUA) is critical to the clinical target volume (CTV) in post-prostatectomy radiotherapy (PPRT), as it is the commonest site of recurrence. Typically, this is performed on a CT alone but guidelines recommend MRI. Objective: To evaluate the VUA spatial differences between CT (ctVUA) and MRI (mrVUA) and analyse its impact on the CT defined CTV (ctCTV) as recommended by published guidelines. Materials and methods: We identified 34 patients with a co-registered simulation CT and T2 weighted MRI. The VUA was located on CT and MRI whilst blinded to the opposing scan. The differences were analysed using Wilcoxon's Signed Rank Test. The mrVUA coverage was investigated using three ctCTV margins of 5 mm, 8 mm and 12 mm. Results: Median age was 63 years with 59% having pT3a disease and median Gleason score of 7. The mrVUA was coincident with the ctVUA in 12% and inferior in 88%. Median difference was 5 mm (010 mm) (P < 0.0001). Only a ctCTV margin of 12 mm would have encompassed all mrVUAs. A ctCTV margin of 8 mm and 5 mm resulted in 12% and 38% cases where the VUA was excluded from the ctCTV. Conclusions: MRI is important for the accurate delineation of VUA for PPRT. (C) 2017 Elsevier B.V. All rights reserved.

OBJECTIVES: To report the outcomes of stereotactic ablative body radiotherapy (SABR) in men with oligometastatic prostate cancer (PCa) diagnosed on prostate-specific membrane antigen (PSMA)-positron emission tomography/computed tomography (PET/CT), based on a single-institution experience and the published literature. PATIENTS AND METHODS: This was a retrospective cohort study of the first 20 consecutive men with oligometastatic PCa, treated with SABR in a single institution, who had biochemical recurrence after previous curative treatment (surgery/radiotherapy), had no evidence of local recurrence, were not on palliative androgen deprivation therapy (ADT), and had PSMA-PET/CT-confirmed oligometastatic disease (≤3 lesions). These men were treated with SABR to a dose of 30 Gy in three fractions for bone metastases, and 35-40 Gy in five fractions for nodal metastases. The outcomes of interest were: PSA response; local progression-free survival (LPFS); distant progression-free survival (DPFS); and ADT-free survival (ADTFS). A literature review was performed to identify published studies reporting on outcomes of PSMA-PET/CT-guided SABR. RESULTS: In our institutional cohort, 12 men (60%) had a decline in PSA post-SABR. One man had local progression 9.6 months post-SABR, with 12-month LPFS of 93%. Ten men had distant progression outside of their SABR treatment field, confirmed on PSMA-PET/CT, with 12-month DPFS of 62%, of whom four were treated with palliative ADT, two received prostate bed radiotherapy for prostate bed progression (confirmed on magnetic resonance imaging), and four received a further course of SABR (of whom one had further progression and was treated with palliative ADT). At last follow-up, six men (one with local progression and five with distant progression) had received palliative ADT. The 12-month ADTFS was 70%. Men with longer intervals between local curative treatment and SABR had better DPFS (P = 0.03) and ADTFS (P = 0.005). Four additional studies reporting on PSMA-PET/CT-guided SABR for oligometastatic PCa were identified and included in the review, giving a total of 346 patients. PSA decline was reported in 60-70% of men post-SABR. The 2-year LPFS, DPFS and ADTFS rates were 76-100%, 27-52%, and 58-62%, respectively. CONCLUSION: Our results showed that PSMA-PET/CT could have an important role in identifying men with true oligometastatic PCa who would benefit the most from metastases-directed therapy with SABR.

Aims Stereotactic body radiotherapy (SBRT) is a locally ablative therapy used for the treatment of patients with spine metastases. However, it is associated with higher rates of vertebral compression fractures (VCF) than conventionally fractionated palliative radiotherapy. The purpose of this study was to determine the rate of VCF following spine SBRT and to identify the risk factors associated with this outcome. Materials and methods We retrospectively reviewed patients treated at two Australian institutions from January 2015 to March 2019. Descriptive statistics were used to assess patient, tumour and treatment factors. The Log-rank test and Cox proportional hazards model were applied in univariate and multivariable analyses to identify factors associated with VCF, local control and overall survival. Results We evaluated 113 spinal segments from 84 patients, with a median follow-up time of 11.9 months. The median dose and fractionation utilised was 30 Gy in three fractions (67.3%), with a single-fraction rate of 0.9%. The median Spinal Instability Neoplastic Score (SINS) of the lesions was 4/18, with most (84.1%) being SINS stable, scoring between 0 and 6. Five VCFs were observed (three progression of pre-existing fractures and two de novo), a cumulative VCF risk of 4.4%. Four of five fractures occurred within the first year after treatment, with a median time to VCF of 9.2 months. A pre-existing VCF (P = 0.011) was associated with subsequent fracture on multivariable analysis, whereas all VCF segments displayed lytic disease appearance. All fractures were managed conservatively with analgesia, without requirement for subsequent surgical intervention. Conclusion SBRT to spine metastases is safe with respect to VCF, with rates around the lower limit observed in similar studies. Knowledge of factors that predispose to post-treatment fracture, such as pre-existing compression, lytic vertebral disease and SINS >6 will aid in the counselling and selection of patients for this therapy.

Germ cell tumors (GCT), accounting for 95% of malignant testicular tumors, can be divided into two groups: seminoma (SGCT) and non-seminoma (NSGCT). Seminomas typically arise in men in the fourth decade of life, compromising 60% of the GCT. At diagnosis, approximately 75% present with local disease (Stage I); 15% is detected with metastatic regional lymph nodes (Stage II) and 5-10% present with juxtaregional or visceral metastasis (Stage III) . This article is protected by copyright. All rights reserved. ispartof: BJU INTERNATIONAL vol:124 issue:1 pages:35-39 ispartof: location:England status: published

Aim To assess the intrafraction motion of the urinary bladder and delineate the appropriate margin size for radiotherapy planning, for both the full and empty bladder. Materials and methods This was a single-site, single-arm study of 20 patients planned to undergo radical cystectomy for histologically confirmed muscle-invasive bladder cancer. Patients underwent magnetic resonance imaging (cineMRI) of the entire pelvis using a 3-Tesla system, prior to cystectomy. Patients first underwent a cineMRI with a full bladder, then voided and underwent a second MRI with an empty bladder. All MRI sequences were acquired over 18 min. We assessed the differences in bladder filling and subsequent bladder wall displacement, between the empty and full bladder, during a time period consistent with radiotherapy treatment delivery. Results Twenty patients underwent cineMRI of the entire pelvis. The maximum mean directional displacements of the bladder walls over the 18 min duration of the scan for the empty bladders were 9.8 mm superiorly, 1.1 mm inferiorly, 2.39 mm anteriorly, 3.73 mm posteriorly, 2.74 mm to the left and 2.48 mm to the right. The maximal mean displacements for the full bladders were 9.2 mm superiorly, 1.1 mm inferiorly, 2.28 mm anteriorly, 1.08 mm posteriorly, 1.85 mm to the left and 1.73 mm to the right. Statistically significant differences were seen in the posterior, left and right displacements but were quantitatively small. Conclusions Intrafractional motion secondary to bladder filling showed minimal variation between the full and empty bladder. Similar clinical target volume to planning target volume margins can be applied for the delivery of radiotherapy for a full and empty bladder.

Background The role of testosterone in maintaining functional performance in older men remains uncertain. Methods We conducted a 12-month prospective, observational case–control study including 34 men newly commencing androgen deprivation therapy for prostate cancer and 29 age-matched prostate cancer controls. Video-based motion capture and ground reaction force data combined with computational musculoskeletal modeling, and data were analyzed with a linear mixed model. Results Compared with controls over 12 months, men receiving androgen deprivation therapy had a mean reduction in circulating testosterone from 14.1 nmol/L to 0.4 nmol/L, associated with reductions in peak knee extension torque, mean adjusted difference (MAD) –0.07 Nm/kg (95% confidence interval [CI]: –0.18, 0.04), p = .009, with a corresponding more marked decrease in quadriceps force MAD –0.11 × body weight (BW) [–0.27, 0.06], p = .045 (equating to a 9 kg force reduction for the mean body weight of 85 kg), and decreased maximal contribution of quadriceps to upward propulsion, MAD –0.47 m/s2 [–0.95, 0.02], p = .009. We observed between-group differences in several other parameters, including increased gluteus maximus force in men receiving androgen deprivation therapy, MAD 0.11 × BW [0.02, 0.20], p = .043, which may be compensatory. Conclusions Severe testosterone deprivation over 12 months is associated with selective deficits in lower-limb function evident with an important task of daily living.

Paraneoplastic syndromes associated with prostate cancer that cause visual disturbances are rare. We present the case of a 71 year old man with a history of adenocarcinoma of the prostate who developed cancer associated retinopathy concomitant with small cell transformation. This represents an unusual paraneoplastic syndrome that may be progressive and irreversible, requiring prompt diagnosis and treatment to preserve visual function and guide further oncological care. Keywords: Prostate cancer, Paraneoplastic, Cancer associated retinopathy

Objective While androgen deprivation therapy (ADT) has been associated with insulin resistance and frailty, controlled prospective studies are lacking. We aimed to examine the relationships between insulin resistance and frailty with body composition and testosterone. Design Case–control prospective study. Methods Sixty three men with non-metastatic prostate cancer newly commencing ADT (n=34) and age-matched prostate cancer controls (n=29) were recruited. The main outcomes were insulin resistance (HOMA2-IR), Fried’s frailty score, body composition by dual x-ray absorptiometry and short physical performance battery (SPPB) measured at 0, 6 and 12months. A generalised linear model determined the mean adjusted difference (95% CI) between groups. Results Compared with controls over 12months, men receiving ADT had reductions in mean total testosterone level (14.1–0.4nmol/L, PPPP=0.02, which was most related to the increase in fat mass (P=0.003), less to lean mass (P=0.09) or total testosterone (P=0.088). Frailty increased with ADT (PP=0.028), and less to fat mass (P=0.056) or lean mass (P=0.79). SPPB was unchanged. Conclusions ADT is associated with increased insulin resistance and frailty within 12months of commencement, independently of confounding effects of cancer or radiotherapy. Insulin resistance appears to be mediated by subcutaneous or peripheral sites of fat deposition. Prevention of fat gain is an important strategy to prevent adverse ADT-associated cardiometabolic risks.

Purpose Radiotherapy plan evaluation is currently performed by assessing physical parameters, which has many limitations. Biological modelling can potentially allow plan evaluation that is more reflective of clinical outcomes, however further research is required into this field before it can be used clinically. Methods A simple program, RADBIOMOD, has been developed using Visual Basic for Applications (VBA) for Microsoft Excel that incorporates multiple different biological models for radiotherapy plan evaluation, including modified Poisson tumour control probability (TCP), modified Zaider–Minerbo TCP, Lyman–Kutcher–Burman normal tissue complication probability (NTCP), equivalent uniform dose (EUD), EUD-based TCP, EUD-based NTCP, and uncomplicated tumour control probability (UTCP). RADBIOMOD was compared to existing biological modelling calculators for 15 sample cases. Results Comparing RADBIOMOD to the existing biological modelling calculators, all models tested had mean absolute errors and root mean square errors less than 1%. Conclusions RADBIOMOD produces results that are non-significantly different from existing biological modelling calculators for the models tested. It is hoped that this freely available, user-friendly program will aid future research into biological modelling.

Introduction This is a retrospective study conducted to report the tumor control and late toxicity outcomes of patients with intermediate-risk prostate cancer undergoing combination external beam radiation therapy and low dose rate brachytherapy (LDR-PB). Methods and Materials Thirty-one patients received 45 Gray (Gy) of external beam radiation therapy to the prostate and seminal vesicles, together with a brachytherapy boost via a transperineal prostate implant of I125 (108 Gy). In addition, some patients received 6 months of androgen deprivation therapy depending on physician preference. Biochemical failure was defined using the Phoenix consensus definition of the nadir PSA +2 ng/mL. Toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0. Results The biochemical progression-free survival, metastases-free survival, and overall survival at 5 years were 87.1%, 96.3%, and 92%, respectively. The incidence of late grade ≥1 and ≥2 genitourinary (GU) toxicities were 54.8% and 6.5%, respectively. The incidence of late grade 3 GU toxicity was 6.5% with urinary retention occurring in two patients requiring either a bladder neck incision or transurethral resection of the prostate. The incidence of late grade ≥1 and 2 gastrointestinal toxicities were 19.4% and 6.5%, respectively. No patients developed grade 3 gastrointestinal toxicity. Conclusion Our small series has shown a high biochemical progression-free survival consistent with the ASCENDE-RT and NRG Oncology/RTOG0232 LDR-PB boost arms. In addition, the risk of late grade 3 GU toxicity is far lower than that reported by the ASCENDE-RT study but comparable to other LDR-PB boost and LDR alone reports in the literature. Therefore, we are comfortable to continue offering LDR-PB boost to our patients with intermediate-risk prostate cancer.

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. 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. 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. 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.

The purpose of this study was to compare the accuracy of [(11)C]choline positron emission tomography (CHOL-PET) with that of the combination of T2-weighted and diffusion-weighted (T2W/DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET.This study included 21 patients who underwent CHOL-PET and T2W/DW MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), and sensitivity and specificity values. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models.The best automatic contouring method, 60% of the maximum SUV (SUV60) , had similar correlations (DSC: 0.59) with the manual PET contours (DSC: 0.52, P=.127) and significantly better correlations than the manual MRI contours (DSC: 0.37, P.001). The sensitivity and specificity values were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET.CHOL-PET is superior to the combination of T2W/DW MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies but may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict how well CHOL-PET delineates IPLs.