BeTTer Outcomes Workgroup Health Quality Initiative to optimize bone health for prostate cancer patients in the British Columbia Cancer System.

INTRODUCTION: Bone-targeted therapies (BTTs) are integral to the management of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). BTTs vary considerably in referral and drug access pathways and optimal BTT use requires multi-specialty consultation and supervision. Health quality improvement (HQI) has become the predominant framework to improve patient care in multidisciplinary settings. METHODS: HQI initiatives on use of BTT in mCRPC were developed and evaluated in five centers of a provincial cancer center network using Plan-Do-Study-Act (PDSA) methodology. Multidisciplinary teams (MDTs) completed a common quality assessment form and an HQI template and then implemented an HQI initiative. Feedback and findings were shared and discussed at regional events. It was subsequently determined whether to adopt, adapt, or abandon initiatives. RESULTS: Patterns of unmet needs varied across type of BTT. Gaps in use of radium-223 were mostly referral and education issues that could be directly addressed at the local level by participating clinician teams. Conversely, most supportive BTT gaps were related to coverage and resourcing support. HQI initiatives selected by each site consisted of implementation or expansion of local MDT meetings, referral documents, databases, and improvement charters. The main HQI initiative was completed in four sites and was adapted or adopted in three. Improvements in BTT use were observed in two of three centers with data on HQI process measures. CONCLUSIONS: Despite the overall heterogenous structure of the groups and metrics used, this study demonstrated that the PDSA framework provides the needed structure for improvements in BTT use in mCRPC across multiple sites.

Treatment Patterns and Outcomes of Preoperative Neoadjuvant Radiotherapy in Patients with Early-onset Rectal Cancer.

Preoperative radiotherapy for early-stage rectal cancer has risks and benefits that may impact treatment choice in young patients. We reviewed radiotherapy use and outcomes for rectal cancer by age. Patients with early-stage rectal cancer in the Canadian province of British Columbia from 2002 to 2016 were identified (n = 6,232). Baseline characteristics, treatment response, overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and locoregional recurrence rate (LRR) were compared between patients <50 (early-onset; n = 532) and ≥50 years old (average-onset; n = 5,700). Early-onset patients were more likely to receive preoperative chemoradiotherapy than short-course radiotherapy [OR, 2.20; 95% confidence interval (CI), 1.67-2.89; P < 0.0001], but also had higher nodal (P = 0.00096) and overall clinical staging (P = 0.033). Cancer downstaging and pathologic complete response rates were similar in those receiving neoadjuvant chemoradiotherapy by age. Early-onset and average-onset patients had similar DSS (P = 0.91) and DFS (P = 0.27) in multivariate analysis unless non-colorectal deaths, which were higher in older patients, were censored in the DFS model (HR, 1.30; 95% CI, 1.01-1.68; P = 0.042). LRR also did not differ between age groups (P = 0.88). Outcomes did not differ based on radiotherapy type. Young patients with rectal cancer are more likely to present with higher staging and receive long-course chemoradiotherapy. DSS did not differ by age group; however, young patients had worse DFS when we censored competing risks of death in older patients. Significance: This population-based study suggests younger patients are more likely to receive chemoradiotherapy, potentially due to higher stage at diagnosis, and response is comparable by age.

A Contouring Strategy and Reference Atlases for the Full Abdominopelvic Bowel Bag on Treatment Planning and Cone Beam Computed Tomography Images.

Purpose: To establish a practical contouring strategy with reference atlases for the abdominopelvic bowel bag on treatment planning computed tomography (TPCT) and cone beam computed tomography (CBCT) images. Methods and Materials: A scoping literature review was done to evaluate the existing definitions and contouring guidelines for bowel bag and small bowel planning-at-risk volume-like structures. A comprehensive definition was proposed for the abdominopelvic bowel bag that expanded the Radiation Therapy Oncology Group Pelvic Normal Tissue Consensus definition. Seven patients with TPCT and first-treatment-day CBCT images were selected from an institutional database to represent a range of normal anatomy and CBCT image quality. The TPCT and CBCT images were contoured using the proposed definition. During contouring, the Radiation Therapy Oncology Group definition's list of inclusion and exclusion structures was expanded. For areas with limited visibility of the bowel bag on either TPCT or CBCT, a set of operational definitions was developed based on consistently visible reference structures. Results: A literature review showed that previously existing bowel bag definitions predominantly focused on the pelvic region and did not provide a complete and practical description of the full abdominopelvic contour relative to structures consistently visible in all radiation therapy images. The proposed contouring strategy had 4 components: a definition, a list of inclusion and exclusion structures, 15 tabulated operational definitions, and a set of atlases. The bowel bag was defined as the peritoneal cavity and retroperitoneal duodenum and ascending and descending colon, as visualized at the time of image acquisition. The operational definitions formalized the location of the peritoneal fascial planes through a simple look-up table. The proposed contouring strategy and reference atlases were successfully used on both TPCT and CBCT images. Conclusions: This study produced a practical contouring strategy and reference atlases to enable reproducible delineation of the full bowel bag on TPCT and CBCT images. The strategy is a necessary first step toward consensus contouring with reduced observer variability, which is a prerequisite for evaluation of cumulative dose and its correlation with toxic effects, adaptive planning strategies, and automated contouring potential.

Centre-specific autonomous treatment plans for prostate brachytherapy using cGANs.

PURPOSE: In low-dose-rate prostate brachytherapy (LDR-PB), treatment planning is the process of determining the arrangement of implantable radioactive sources that radiates the prostate while sparing healthy surrounding tissues. Currently, these plans are prepared manually by experts incorporating the centre's planning style and guidelines. In this article, we develop a novel framework that can learn a centre's planning strategy and automatically reproduce rapid clinically acceptable plans. METHODS: The proposed framework is based on conditional generative adversarial networks that learn our centre's planning style using a pool of 931 historical LDR-PB planning data. Two additional losses that help constrain prohibited needle patterns and produce similar-looking plans are also proposed. Once trained, this model generates an initial distribution of needles which is passed to a planner. The planner then initializes the sources based on the predicted needles and uses a simulated annealing algorithm to optimize their locations further. RESULTS: Quantitative analysis was carried out on 170 cases which showed the generated plans having similar dosimetry to that of the manual plans but with significantly lower planning durations. Indeed, on the test cases, the clinical target volumes achieving [Formula: see text] of the prescribed dose for the generated plans was on average [Formula: see text] ([Formula: see text] for manual plans) with an average planning time of [Formula: see text] min ([Formula: see text] min for manual plans). Further qualitative analysis was conducted by an expert planner who accepted [Formula: see text] of the plans with some changes ([Formula: see text] requiring minor changes & [Formula: see text] requiring major changes). CONCLUSION: The proposed framework demonstrated the ability to rapidly generate quality treatment plans that not only fulfil the dosimetric requirements but also takes into account the centre's planning style. Adoption of such a framework would save significant amount of time and resources spent on every patient; boosting the overall operational efficiency of this treatment.

Prostate brachytherapy intraoperative dosimetry using a combination of radiographic seed localization with a C-arm and deformed ultrasound prostate contours.

PURPOSE: The purpose of the study was to assess the feasibility of performing intraoperative dosimetry for permanent prostate brachytherapy by combining transrectal ultrasound (TRUS) and fluoroscopy/cone beam CT [CBCT] images and accounting for the effect of prostate deformation. METHODS AND MATERIALS: 13 patients underwent TRUS and multiview two-dimensional fluoroscopic imaging partway through the implant, as well as repeat fluoroscopic imaging with the TRUS probe inserted and retracted, and finally three-dimensional CBCT imaging at the end of the implant. The locations of all the implanted seeds were obtained from the fluoroscopy/CBCT images and were registered to prostate contours delineated on the TRUS images based on a common subset of seeds identified on both image sets. Prostate contours were also deformed, using a finite-element model, to take into account the effect of the TRUS probe pressure. Prostate dosimetry parameters were obtained for fluoroscopic and CBCT-dosimetry approaches and compared with the standard-of-care Day-0 postimplant CT dosimetry. RESULTS: High linear correlation (R2 > 0.8) was observed in the measured values of prostate D90%, V100%, and V150%, between the two intraoperative dosimetry approaches. The prostate D90% and V100% obtained from intraoperative dosimetry methods were in agreement with the postimplant CT dosimetry. Only the prostate V150% was on average 4.1% (p-value <0.05) higher in the CBCT-dosimetry approach and 6.7% (p-value <0.05) higher in postimplant CT dosimetry compared with the fluoroscopic dosimetry approach. Deformation of the prostate by the ultrasound probe appeared to have a minimal effect on prostate dosimetry. CONCLUSIONS: The results of this study have shown that both of the proposed dosimetric evaluation approaches have potential for real-time intraoperative dosimetry.

Automatic detection of brachytherapy seeds in 3D ultrasound images using a convolutional neural network.

A novel approach for automatic localization of brachytherapy seeds in 3D transrectal ultrasound (TRUS) images, using machine learning based algorithm, is presented. 3D radiofrequency ultrasound signals were collected from 13 patients using the linear array of the TRUS probe during the brachytherapy procedure in which needles are used for insertion of stranded seeds. Gold standard for the location of seeds on TRUS data were obtained with the guidance of the complete reconstruction of the seed locations from multiple C-arm fluoroscopy views and used in the creation of the training set. We designed and trained a convolutional neural network (CNN) model that worked on 3D cubical sub-regions of the TRUS images, that will be referred to as patches, representing seed, non-seed within a needle track and non-seed elsewhere in the images. The models were trained with these patches to detect the needle track first and then the individual seeds within the needle track. A leave-one-out cross validation approach was used to test the model on the data from eight of the patients, for whom accurate seed locations were available from fluoroscopic imaging. The total inference time was about 7 min for needle track detection in each patient's image and approximately 1 min for seed detection in each needle, leading to a total seed detection time of less than 15 min. Our seed detection algorithm achieved [Formula: see text] precision, [Formula: see text] recall and [Formula: see text] F1_score. The results from our CNN-based method were compared to manual seed localization performed by an expert. The CNN model yielded higher precision (lower false discovery rate) compared to the manual method. The automated approach requires little modification to the current clinical setups and offers the prospect of application in real time intraoperative dosimetric analysis of the implant.

Exposure to radiation and medical oncology training: A survey of Canadian urology residents and fellows.

INTRODUCTION: Residency experiences and teaching in oncology among urology residents are variable across Canada. We sought to identify how radiation and medical oncology concepts, as they pertain to genitourinary malignancies, are taught to urology residents. METHODS: A total of 190 trainees enrolled in Canadian urology residency training programs were invited to participate in the study from January 2016 to June 2016. Participants completed an online questionnaire addressing the training they received. RESULTS: The overall response rate was 32%. Twenty-three percent of respondents were in their fellowship year; 17%, 20%, 10%, 17%, and 12% were first-, second-, third-, fourth-, and fifth-year residents, respectively, with a median of four (range 1-9) respondents from each training program. Ninety-five percent of respondents had academic half-day (AHD) as part of their training that included radiotherapy (61%) and chemotherapy (51%) teaching. Most respondents indicated their main exposure to chemotherapy and radiation came from informal teaching in urology clinics. Twenty-nine percent and 41%, of participants had mandatory rotations in radiation and medical oncology, respectively. Only 6% of respondents used their voluntary elective time in these disciplines and most voluntary electives were of 1-2-week duration. Despite this, 90% of respondents preferred some mandatory radiation and medical oncology training. CONCLUSIONS: Most of the limited exposure that urology residents have to medical and radiation oncology is through AHD or informal urology clinics, despite a desire among current urology trainees to have clinical exposure in these areas. Moving forward, urology residency programs should consider integrating medical and radiation oncology rotations into the residency program curriculum.

Appropriate timing for postimplant imaging in permanent breast seed implant: Results from a serial CT study.

PURPOSE: Postimplant analysis in permanent breast seed implant (PBSI) is performed at inconsistent times subsequent to seed implantation across cancer centers, creating challenges in the interpretation of dosimetric data and ultimately the correlation with clinical outcomes. The purpose of this study is to determine the most appropriate time postimplant to perform this analysis. METHODS AND MATERIALS: Nine patients treated at our institution with PBSI were included in this analysis. Each underwent 4 postimplant CT scans: 0, 15, 30, and 60 days postimplant. A model of the accumulated dose was created by deformably registering the Day 15, 30, and 60 postimplant CT scans and dose matrices to the Day 0 scan, scaling for seed decay. The results from this model were compared to each individual postplan by integral comparison of dose-volume histogram curves for a dose evaluation volume. RESULTS: The Day 30 postplan showed the best agreement with the accumulated dose model and the smallest interpatient variability across the patient cohort. The mean (±SD) for the dose evaluation volume V90, V100, V150, and V200 for the accumulated dose model was 90 ± 7%, 86 ± 8%, 66 ± 14%, and 41 ± 16%, respectively. CONCLUSIONS: Based on the results of this patient cohort, we recommend that postimplant dosimetric analysis for PBSI be performed approximately 30 days following the implant.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study.

PURPOSE: To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). MATERIAL AND METHODS: Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. RESULTS: Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. CONCLUSIONS: Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB.

Institutional long-term outcomes at the first Canadian center performing intraoperatively planned low-dose-rate brachytherapy alone in low- and intermediate-risk prostate cancer.

PURPOSE: The aim of this study is to report the long-term outcomes and toxicities from a large cohort of patients with localized prostate cancer treated with low-dose-rate intraoperatively planned brachytherapy. METHODS AND MATERIALS: Prostate-specific antigen levels, urinary symptoms, and erectile function were recorded at baseline, and each followup visit was then entered into a prospective database. Urinary toxicity requiring procedural intervention was retrospectively verified using an integrated electronic medical system. A separate cross-sectional survey was performed to measure postimplant sexual function. RESULTS: A total of 822 patients with low and favorable intermediate-risk prostate cancer were treated at our institution between 2003 and 2013. The Kaplan-Meier estimates for biochemical recurrence for our cohort were 95% and 87% at 5 and 10 years, respectively. Cystoscopy, transurethral resection of prostate, or dilatation was required for 7.1% of 720 patients with more than 2 years of followup. At a median followup of 3.7 years, 64.4% of patients retained adequate erectile function for intercourse, with 54% of patients who were no longer sexually active postimplant reporting social factors as the primary reason. CONCLUSIONS: Our institutional experience with intraoperative low-dose-rate prostate brachytherapy yielded excellent long-term results with a low incidence of urinary and sexual toxicity.

Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study.

PURPOSE: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). METHODS AND MATERIALS: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with ClinicalTrials.gov (clinicaltrials.gov identifier NCT01046123). RESULTS: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient. CONCLUSIONS: For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases.

Population-based 10-year event-free survival after radical prostatectomy for patients with prostate cancer in British Columbia.

INTRODUCTION: We determined (1) the 10-year survival outcomes after radical treatment of prostate cancer and (2) the 10-year event-free survival following radical prostatectomy (RP) at a population-level in British Columbia (BC), Canada. METHODS: We identified all men with a new diagnosis of prostate cancer in BC between 1999 and 2000. Those treated with RP, external beam radiotherapy (EBRT) or brachytherapy (BT) were identified. Overall survival, and prostate cancer specific survival (PCSS) were calculated from diagnosis using the Kaplan-Meier method. For those men treated with RP, we calculated the 10-year event-free survival (freedom from salvage EBRT or androgen ablation, or death from prostate cancer). Reasons for initiating androgen therapy were unknown and may include symptomatic metastatic disease or asymptomatic biochemical recurrence. An important limitation was the absence of prostate-specific antigen data for staging or follow-up. RESULTS: Among 6028 incident cases, RP was the curative-intent treatment within 1 year in 1360 (22.6%) patients, EBRT in 1367 (22.7%), and BT in 357 (5.9%). The 10-year PCSS was 98% for RP, 95% for EBRT and 98% for BT (log rank p < 0.0001). The 10-year overall survival was 87%. The 10-year event-free survival for those treated with RP was 79% and varied with Gleason grade: 87%, 74%, and 52% for Gleason 2-6, 7, and 8-10, respectively (p < 0.0001). CONCLUSIONS: This population-based study provides outcomes which can inform patient decision-making and provide a benchmark to which other therapies can be compared. Event-free rates for patients treated with RP vary with Gleason score. There is room for improvement in the outcomes of patients with high Gleason score treated with RP.

Secondary sarcoma of bone post-prostate brachytherapy: A case report.

Malignancies associated with brachytherapy for prostate cancer are largely unreported in the literature. We report a case of post-brachytherapy osteogenic sarcoma in the pelvis 6 years after permanent (125)I implant for intermediate-risk prostate cancer. The patient was treated with neoadjuvant chemotherapy, limb-sparing surgical resection and postoperative radiation therapy for unexpected positive margins.

The need for, and utilization of prostate-bed radiotherapy after radical prostatectomy for patients with prostate cancer in British Columbia.

INTRODUCTION: Three randomized trials have demonstrated that post-radical prostatectomy (RP) radiotherapy decreases biochemical relapse for those with adverse pathology. Our purpose was to describe the incidence of pathologic risk factors for recurrence in a contemporary series of patients treated with RP and to describe the use of post-RP radiotherapy. METHODS: All incident prostate cancers diagnosed between January 2005 and December 2007 were identified from the tumour registry. Cases were then linked to radiotherapy records which included dose and modality (external beam radiotherapy and brachytherapy). The pathology reports in the tumour registry were reviewed for pathologic stage, grade and margin status. RESULTS: We identified 9223 patients with prostate cancer. Overall, 36.3% of patients treated with RP had positive margins, and may have benefited from adjuvant radiotherapy. After RP, 332 (15%) patients had radiotherapy to the prostate bed; of these, only 25 (1.1%) received truly adjuvant radiotherapy (delivered within 6 months with a prostate-specific antigen of <0.2 ng/mL). Of the 2181 patients treated with RP, 270 (12%) were seen by a radiation oncologist within 6 months of RP. Of the 1015 patients (47%) with adverse RP pathology (positive margins, extracapsular extension or seminal vesicle invasion), 230 (23%) were seen by a radiation oncologist within 6 months of RP. CONCLUSION: Not all patients with adverse prostatectomy pathology were seen by a radiation oncologist post-prostatectomy, and very few received adjuvant radiotherapy despite almost half of them having risk factors for relapse.

Hierarchical clustering analysis of tissue microarray immunostaining data identifies prognostically significant groups of breast carcinoma.

Prognostically relevant cluster groups, based on gene expression profiles, have been recently identified for breast cancers, lung cancers, and lymphoma. Our aim was to determine whether hierarchical clustering analysis of multiple immunomarkers (protein expression profiles) improves prognostication in patients with invasive breast cancer. A cohort of 438 sequential cases of invasive breast cancer with median follow-up of 15.4 years was selected for tissue microarray construction. A total of 31 biomarkers were tested by immunohistochemistry on these tissue arrays. The prognostic significance of individual markers was assessed by using Kaplan-Meier survival estimates and log-rank tests. Seventeen of 31 markers showed prognostic significance in univariate analysis (P < or = 0.05) and 4 markers showed a trend toward significance (P < or = 0.2). Unsupervised hierarchical clustering analysis was done by using these 21 immunomarkers, and this resulted in identification of three cluster groups with significant differences in clinical outcome. chi2 analysis showed that expression of 11 markers significantly correlated with membership in one of the three cluster groups. Unsupervised hierarchical clustering analysis with this set of 11 markers reproduced the same three prognostically significant cluster groups identified by using the larger set of markers. These cluster groups were of prognostic significance independent of lymph node metastasis, tumor size, and tumor grade in multivariate analysis (P=0.0001). The cluster groups were as powerful a prognostic indicator as lymph node status. This work demonstrates that hierarchical clustering of immunostaining data by using multiple markers can group breast cancers into classes with clinical relevance and is superior to the use of individual prognostic markers.