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Working parents, and a rising number of adults delivering care for ageing relatives, experience numerous challenges in their personal, family, professional and financial lives due to multiple responsibilities. This study describes the experiences of Canadian radiation oncology (RO) parents and family caregivers, reporting challenges that may exist in providing family care with clinical/academic work commitments.Canadian RO's were invited to participate in an anonymous online survey, via RO heads of departments in cancer centres across Canada and to physician members of the Canadian Association of Radiation Oncology between November 2021 and January 2022. The survey focused on demographics, experiences of pregnancy and leave, parenting and adult caregiving responsibilities, and self-care.103 (38%) staff RO completed the survey, 78 (75.7%) identified as having a parental (76, 89.7%) and/or other family caregiver (8, 10.3%) role. 41% were female (59% male), with no difference between gender and number of children (median 2, IQR 1-3, p=0.17). More female respondents took parental leave for their first child compared to male (mean 29 versus 6 weeks, p0.001). 27% of male respondents who started caring for their first child during residency took parental leave compared to 77% (p=0.003) as a staff. The majority of respondents described "always/usually" collegial support for each pregnancy and parental leave. Both genders described parental responsibilities as negatively impacting attendance at conferences (male - 65%, female - 77%, p=0.31) and early/late work-related meetings (male - 76%, female 79%, p=1.0). More female respondents described parental responsibilities as negatively impacting their career (50% vs 29%, p=0.085). 52% of female respondents (vs 26% male respondents, p=0.044) identified a physician mentor or positive role model around parenting issues.Parental and other family caregiving responsibilities are not gender unique in Canadian ROs but competing work and family roles may impact genders differently.

To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB).A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial.The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p0.001), 73 ± 8% (p0.001), and 77 ± 9% (p = 0.098) for the ineligible patients.In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. Materials and Methods: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. Results: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2–3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Conclusion: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

Purpose: The presence of intrinsic radiosensitivity within prostate cancer patients may be an important factor contributing to development of radiation toxicity. We investigated whether variants in genes responsible for detecting and repairing DNA damage independently contribute to toxicity following prostate brachytherapy.Experimental Design: Genomic DNA was extracted from blood samples of 41 prostate brachytherapy patients, 21 with high and 20 with low late toxicity scores. For each patient, 242 PCR amplicons were generated containing 173 exons of eight candidate genes: ATM, BRCA1, ERCC2, H2AFX, LIG4, MDC1, MRE11A, and RAD50. These amplicons were sequenced and all sequence variants were subjected to statistical analysis to identify those associated with late radiation toxicity.Results: Across 41 patients, 239 sites differed from the human genome reference sequence; 170 of these corresponded to known polymorphisms. Sixty variants, 14 of them novel, affected protein coding regions and 43 of these were missense mutations. In our patient population, the high toxicity group was enriched for individuals with at least one LIG4 coding variant (P = 0.028). One synonymous variant in MDC1, rs28986317, was associated with increased radiosensitivity (P = 0.048). A missense variant in ATM, rs1800057, associated with increased prostate cancer risk, was found exclusively in two high toxicity patients but did not reach statistical significance for association with radiosensitivity (P = 0.488).Conclusions: Our data revealed new germ-line sequence variants, indicating that existing sequence databases do not fully represent the full extent of sequence variation. Variants in three DNA repair genes were linked to increased radiosensitivity but require validation in larger populations.

Supplementary Data from Sequence Variant Discovery in DNA Repair Genes from Radiosensitive and Radiotolerant Prostate Brachytherapy Patients

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 Conclusions The results of this study have shown that both of the proposed dosimetric evaluation approaches have potential for real-time intraoperative dosimetry.

Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P.001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up.Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received anThe 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P.001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm.Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

To evaluate the prevalence of burnout among brachytherapy specialists and to identify factors associated with burnout.An anonymous, online, cross-sectional survey was administered to non-trainee physician members of the American Brachytherapy Society. Burnout was evaluated using the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Demographic and practice-specific questions were collected from respondents. Univariate and multivariable analysis of outcomes were performed using probabilistic index models.Overall, 51 of 400 physicians responded (13% response rate). Fifty-seven percent of respondents demonstrated at least one symptom of professional burnout. However, only 6% of respondents met strict criteria for high burnout. Analysis of the individual MBI-HSS subdomains demonstrated higher subscale scores for emotional exhaustion and depersonalization, but also higher scores for personal accomplishment. On multivariable analysis after adjusting for increased feelings of burnout due to the COVID-19 pandemic or total hours of work per week, younger age was associated with both increased subscale scores for emotional exhaustion (p = 0.026) and lower personal accomplishment (p = 0.010). Lastly, nearly half of all respondents (47%) reported increased feelings of burnout due to the COVID-19 pandemic. Respondents from academic facilities were significantly more likely to report increased burnout due to COVID-19 compared to those from non-academic facilities (odds ratio, 7.04; 95% CI 1.60-31.0; p = 0.010).Nearly 60% of brachytherapists demonstrated symptoms of professional burnout, which is higher than other radiation oncology groups (academic chairs, program directors, residents). Managing stressors related to workload, COVID and support for junior physicians are potential areas for improving feelings of burnout.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

The aim of this study was to characterize the patterns of prostate cancer recurrence after brachytherapy (BT) using 2-(3-[1-carboxy-5-([6-Patients were selected from an ongoing prospective institutional trial investigating the use of [Between March 2017 and April 2020, 670 patients underwent [Contrary to previous evidence, our study suggests that in prostate BT patients with biochemical recurrence, the most common site of failure is local for the patients treated with monotherapy and metastatic for patients treated with a combination of external beam radiation and BT boost.

PURPOSE The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen

Purpose/objective(s) In 2018, the Canadian Medical Association acknowledged that physician health remains a significant threat to the viability of Canada's health care system. The prevalence of burnout among American oncologists was 44% in a 2014 survey. The purpose of this survey was to determine the national prevalence of burnout indicators and report work engagement among Canadian radiation oncologists. Materials/methods Between November 2019 and March 2020 (pre-COVID pandemic), an online questionnaire was distributed electronically to 333 Canadian radiation oncologists across 49 centers through the Stadt lander Canadian Association of Radiation Oncology mailing list. The survey included 62 questions assessing work engagement, and the validated Maslach Burnout Inventory (MBI) burnout scale (22 questions). Results 241 of the 333 surveyed Canadian radiation oncologists (72%) completed the questionnaire and were included in this analysis. Responses to the MBI showed that 15% of radiation oncologists met the strict criteria for burnout (i.e., negative scores in all 3 domains: exhaustion, depersonalization, and low accomplishment). Another 60% scored negative in at least one of the three burnout domains. Using the more commonly reported definition of burnout (negative scores in either exhaustion and/or depersonalization), 44% of Canadian radiation oncologists were burnt out. Only 25% had positive scores in all 3 domains and were fully engaged in their work. The full burnout syndrome varied between provinces and was the highest in British Columbia (22%) and lowest in Quebec (3%). The responses to work engagement questions revealed significant concerns regarding inefficiency in workflow (50%), heavy workloads (> 50%), poor work life balance (68%), lack of control over the work environment (47%) and lack of recognition from administrators (45%). 48% perceive the atmosphere at their primary work area as "chaotic and hectic". Within the last 3 years, 41% had considered leaving their institution to work elsewhere and 51% were considering reducing their full-time equivalent (FTE). Reassuringly, 80% reported a sense of overall ability to provide high quality care and a 59% feel they have a supportive network of colleagues and 80% are willing to try something new. The top 4 strategies identified by respondents aimed to improve work-life quality were (1) more support staff at work, (2) more efficient care models, (3) more resources for patients, and (4) lighter workloads for physicians. Conclusion Our survey showed that only 25% of Canadian radiation oncologists are fully engaged in their work, whereas 15% met the strict criteria for burnout and 44% met the commonly used burnout criteria. With the rising incidence of cancer and complexity of care, there is an urgent need for system change, leverage enthusiasm to "try something new", and develop appropriate strategies to improve the well-being of the Canadian radiation oncologist workforce.

Purpose Education and training on prostate brachytherapy for radiation oncology and medical physics residents in the United States is inadequate, resulting in fewer competent radiation oncology personnel to perform implants, and is a factor in the subsequent decline of an important, potentially curative cancer treatment modality for patients with cancer. The American Brachytherapy Society (ABS) leadership has recognized the need to establish a sustainable medical simulation low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy workshop program that includes physician–physicist teams to rapidly translate knowledge to establish high-quality brachytherapy programs. Methods The ABS, in partnership with industry and academia, has held three radiation oncology team–based LDR/HDR workshops composed of physician–physicist teams in Chicago in 2017, in Houston in 2018, and in Denver in 2019. The predefined key metric of success is the number of attendees who returned to their respective institutions and were actively performing brachytherapy within 6 months of the prostate brachytherapy workshop. Results Of the 111 physician/physicist teams participating in the Chicago, Houston, and Denver prostate brachytherapy workshops, 87 (78%) were actively performing prostate brachytherapy (51 [59%] HDR and 65 [75%] LDR). Conclusions The ABS prostate brachytherapy LDR/HDR simulation workshop has provided a successful education and training structure for medical simulation of the critical procedural steps in quality assurance to shorten the learning curve for delivering consistently high-quality brachytherapy implants for patients with prostate cancer. An ABS initiative, intended to bend the negative slope of the brachytherapy curve, is currently underway to train 300 new competent brachytherapy teams over the next 10 years.

Research suggests that the information needs of patients diagnosed with head and neck cancer can be particularly complex, given the frequent need for multidisciplinary treatments and resulting potential for profound functional impairments. This study was designed to identify head and neck cancer patients' reported informational needs and to evaluate their satisfaction with the written information they received. The study was divided into 2 phases: phase 1, prior to development of a new educational pamphlet, and phase 2, after its implementation. A survey was designed to evaluate several measures including content, amount, understanding, and timing of information delivery. It was distributed at two points during patients' treatment pathway for each phase: at their last radiation appointment and at their posttreatment follow-up appointment. Participant responses after the revised pamphlet indicated greater preparedness before their first treatment, as well as increased satisfaction with treatment option information. Most were satisfied with information timing, but about a third did indicate that additional information would have been helpful at variable time points. Open-ended responses demonstrated that overall, patients do still desire more information, particularly on side effect and self-care management information. While patients with head and neck cancer appear to be generally satisfied with the written information received, our findings suggest that there is still considerable variability in how the information is understood, when it should be delivered, and in which areas more would have been beneficial. These findings underscore the need to consider how best to balance available resources in order to provide more tailored yet comprehensive education for this group of patients.

Background and purpose To identify a PSA threshold value at an intermediate follow-up time after low dose rate (LDR) prostate brachytherapy associated with cure, defined as long-term (10–15 year) freedom from prostate cancer. Materials and methods Data from 7 institutions for 14,220 patients with localized prostate cancer treated with LDR brachytherapy, either alone (8552) or with external beam radiotherapy (n = 1175), androgen deprivation (n = 3165), or both (n = 1328), were analyzed. Risk distribution was 42.4% favorable, 49.2% intermediate, and 8.4% high-risk. Patients with clinical failure before 3.5 years were excluded. Kaplan-Meier analysis was used with clinical failure (local, distant, regional or biochemical triggering salvage) as an endpoint for each of four PSA categories: PSA ≤ 0.2, >0.2 to ≤0.5, >0.5 to ≤1.0, and >1.0 ng/mL. PSA levels at 4 years (±6 months) in 8746 patients without clinical failure were correlated with disease status at 10–15 years. Results For the 77.1% of patients with 4-year PSA ≤ 0.2, the freedom-from-recurrence (FFR) rates were 98.7% (95% CI 98.3–99.0) at 10 years and 96.1% (95% CI 94.8–97.2) at 15 years. Three independent validation cohorts confirmed 97–99% 10-year FFR rates with 4-year PSA ≤ 0.2. Successive PSA categories were associated with diminished disease-free rates at 10 and 15 years. PSA category was strongly associated with treatment success (p Conclusions Since 98.7% of patients with PSA ≤ 0.2 ng/mL at 4 years after LDR prostate brachytherapy were disease-free beyond 10 years, we suggest adopting this biochemical definition of cure for patients with ≥4 years’ follow-up after LDR brachytherapy.

Purpose: National studies suggest over fifty percent of physicians have feelings of burnout (Shanafelt et. al. Mayo Clin Proc 2015). This can result in emotional exhaustion, depersonalization, and reduced personal accomplishment. Left unmanaged this can lead to depression, addiction, and suicidal ideation. Burnout rates are reported for radiation oncology residents, program directors, and academic chairs but not amongst radiation oncologists who practice brachytherapy. The purpose of this study was to determine the rates of burnout amongst physician members of the American Brachytherapy Society (ABS). Materials and Methods: An anonymous online cross-sectional survey was performed of ABS physician members from December 2020 to February 2021. The survey was initially emailed from the ABS to members, followed by two participation reminders. Burnout was assessed by the Maslach Burnout Inventory-Human Service Survey (MBI-HSS), a validated 22-question survey. Thirteen additional demographics questions were included. High emotional exhaustion (EE) was defined a score of at least 27, high depersonalization was defined as a score of at least 10, and low personal accomplishment (PA) was defined by a score of no more than 33 (Rotenstein et. al. JAMA 2018). This study was approved by the Institutional Review Board. Results: Overall, 51 out of 400 members responded to the survey (13% response rate). Respondents were predominantly male (69%), married (78%), had 1-5 full time faculty or partners (59%), worked 51-60 hours per week (61%), deliver 6-10 brachytherapy treatments per week (43%), and have a brachytherapy suite in their department (63%). Six percent of respondents met the strict MBI-HSS criteria for high burnout (as defined by high EE, high DP, and low PA). Fifty-seven percent of respondents reported at least one manifestation of professional burnout (either high EE or DP). Based on individual MBI-HSS subscale scores, 47% of respondents demonstrated high EE, 37% high DP, and 16% low PA. Compared to prior surveys of radiation oncology academic chairs, residency program directors, and residents, survey respondents consistently had higher mean scores for EE and higher scores for DP, but higher scores for PA (Table 1). The most common identified stressors were electronic medical records (EMR) and excessive workload. Forty-seven percent of respondents also reported that COVID-19 increased their feelings of burnout. Respondents from academic facilities were more likely to have increased feelings of burnout due to COVID-19 (odds ratio 6.8, 95% CI 1.8-25.7). Conclusions: Nearly 60% of ABS physician members who responded to this survey reported symptoms of professional burnout with 6% meeting strict criteria for high burnout. This is higher than that reported for radiation oncology residents, program directors, or academic chairs. Managing stressors related to the EMR and workload are potential areas for improvement.

Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long-term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold.A total of 2,339 patients with low or intermediate risk prostate cancer receivedAt a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort.Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous.

This study investigates whether Genomic Organization at Large Scales (which we propose to call GOALS) as quantified via nuclear phenotype characteristics and cell sociology features (describing cell organization within tissue) collected from prostate tissue microarrays (TMAs) can separate biochemical failure from biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of the 78 prostate cancer tissue cores collected from patients treated with RP, 16 who developed biochemical relapse (failure group) and 16 who were BNED patients (nonfailure group) were included in the analyses (36 cores from 32 patients). A section from this TMA was stained stoichiometrically for DNA using the Feulgen-Thionin methodology, and scanned with a Pannoramic MIDI scanner. Approximately 110 nuclear phenotypic features, predominately quantifying large scale DNA organization (GOALS), were extracted from each segmented nuclei. In addition, the centers of these segmented nuclei defined a Voronoi tessellation and subsequent architectural analysis. Prostate TMA core classification as biochemical failure or BNED after RP using GOALS features was conducted (a) based on cell type and cell position within the epithelium (all cells, all epithelial cells, epithelial >2 cell layers away from basement membrane) from all cores, and (b) based on epithelial cells more than two cell layers from the basement membrane using a Classifier trained on Gleason 6, 8, 9 (16 cores) only and applied to a Test set consisting of the Gleason 7 cores (20 cores). Successful core classification as biochemical failure or BNED after RP by a linear classifier was 75% using all cells, 83% using all epithelial cells, and 86% using epithelial >2 layers. Overall success of predicted classification by the linear Classifier of (b) was 87.5% using the Training Set and 80% using the Test Set. Overall success of predicted progression using Gleason score alone was 75% for Gleason >7 as failures and 69% for Gleason >6 as failures. © 2017 International Society for Advancement of Cytometry.

The long-term risk of secondary malignancy is a potential late effect of brachytherapy. However, the time interval, anatomic site and histopathology are not well studied. We sought to characterize the bladder cancers that developed following treatment of prostate cancer with brachytherapy. Between 1998 and 2014, 4570 patients were treated with brachytherapy at the BC Cancer Agency. Out of those, 69 patients subsequently developed bladder cancer, some of which could have been radiation induced. Histology slides were reviewed for all cases, and site and pathologic features were recorded. Cases were classified as luminal and basal subtypes based on GATA3 and CK5/6 immunohistochemistry. Bladder neck and trigone were among the common sites of involvement. Pathologic review of cases showed that 68 % were high-grade, 25 % were muscle-invasive, and 20 % showed variant histology, including small cell carcinoma, sarcomatoid carcinoma, squamous cell carcinoma, and adenocarcinoma. A subgroup of cases more likely to be radiation-induced, based on site and time interval, was associated with increased pathologic stage (pT1 or higher) compared to the other cases (70 % vs 34 %, p = 0.01). In conclusion, the majority of bladder cancers following brachytherapy in this cohort were of high grade and low stage at diagnosis, most of them demonstrating luminal immunophenotype. A significant number of variant histologies are seen, each demonstrating a specific immunophenotype.

Purpose High-dose-rate (HDR) brachytherapy is a convenient treatment option for selected patients with T1-T2 penile squamous cell carcinoma (SCC), providing high rates of penile preservation and tumor control. We present the results of penile SCC treated with HDR brachytherapy either interstitially or via a surface mold. Methods and Materials Between November 2009 and April 2019, seven patients (2 T1a and 5 T2) were treated with interstitial HDR and 8 (1 Tis, six T1a, and one T1b) with surface mold. Prescribed dose for interstitial patients ranged from 38.4 Gy in 6 days (3.2 Gy × 12) to 53 Gy in 9 days (3.12 × 17), BID. All patients treated with mold brachytherapy received 40 Gy in 10 fractions BID. Toxicity and oncological results were assessed for both groups, and their relation with dosimetry is described. Results Median follow up was 90 months for interstitial and 27 months for those treated with surface mold. Fourteen of 15 patients are alive and disease-free; one surface mold patient died of non-small-cell lung cancer. There was one relapse in each group, each treated with salvage penectomy. The potency was preserved in 82%. For interstitial, G2 necrosis occurred in 43%, G2 meatal stenosis in 29% and G3 stenosis in 14%. Conclusions Both techniques have excellent rates of tumor control and organ preservation. Implant geometry and homogeneity constraints must be carefully designed to minimize toxicity in interstitial brachytherapy. Urethral contouring and reporting of dosimetric parameters should be defined.

Background: The Canadian Medical Association recently acknowledged that physician health remains a significant threat to the viability of Canada's health care system. A 2014 survey reported a 44% prevalence of burnout among American oncologists. The purpose of this survey was to determine the national prevalence of burnout and document work engagement among Canadian radiation oncologists. Methods: Between November 2019 and March 2020 (pre COVID pandemic), an online questionnaire was distributed electronically to 333 Canadian radiation oncologists, across 49 centers, through the National Canadian Association of Radiation Oncology membership list. The survey included 62 questions determining job engagement, and validated burnout scale The Maslach Burnout Inventory (MBI) (22 questions). Results: 241 of the 333 surveyed Canadian radiation oncologists (72%) completed the questionnaire and were included in this analysis. Responses to the MBI showed that 15% of radiation oncologists met the strict criteria for burnout (i.e. negative scores in all 3 domains: exhaustion, depersonalization, and low accomplishment). Another 60% scored negative in at least one of the three burnout domains. Using the more commonly reported definition of burnout (negative scores in either exhaustion and/or depersonalization), 44% of Canadian radiation oncologists were burnt out. Only 25% had positive scores in all 3 domains and were fully engaged in their work. The full burnout syndrome varied between provinces and was the highest in British Columbia (22%) and lowest in Quebec (3%). The responses to work engagement questions revealed significant concerns regarding inefficiency in work flow (50%), heavy workloads (>50%), poor work life balance (68%), lack of control over the work environment (47%) and lack of recognition from administrators (45%). 48% perceive the atmosphere at their primary work area as “chaotic and hectic”. Within the last 3 years, 41% had considered leaving their institution to work elsewhere and 51% were considering reducing their full-time equivalent (FTE). Reassuringly, 80% reported a sense of overall ability to provide high quality care and a 59% feel they have a supportive network of colleagues and 80% are willing to try something new. The top 4 strategies identified by respondents aimed to improve work-life quality were (1) more support staff at work, (2) more efficient care models, (3) more resources for patients, and (4) lighter workloads for physicians. Conclusion: The survey shows that only 25% of the Canadian radiation oncologists are fully engaged in their work, 15 % meet the strict criteria for burnout and 44% meet the more commonly used burnout criteria. With the rising incidence of cancer and complexity of care, there is an urgent need for change, leverage the enthusiasm to “try something new”, and develop appropriate strategies to improve the well-being of the oncology work force.

Radiation induced rectal ulcers and fistulas are rare but significant complications of low dose rate prostate brachytherapy for localized prostate cancer. We describe the incidence of ulcers and fistulas, and associated risk factors.We reviewed the records of 4,690 patients with localized prostate cancer who were treated with low dose rate (125)I prostate brachytherapy to a dose of 144 Gy with or without 6 months of androgen deprivation therapy. Patient, disease, comorbidity, treatment, dosimetric and posttreatment intervention factors were analyzed for an association with ulcer or fistula formation.At a median followup of 53 months 21 cases were identified, including 15 rectal ulcer cases, of which 6 progressed to fistulas, and an additional 6 cases of fistulas with no prior documented ulcers. Overall 9 rectal ulcer cases (0.19%) and 12 fistula cases (0.26%) were identified. In 8 of 15 patients ulcers healed with conservative management. No fistulas healed without surgical management. Two patients with fistulas died. Eight patients diagnosed with rectal ulcers subsequently underwent rectal biopsies, after which fistulas developed in 3. One patient with a de novo fistula underwent a preceding biopsy. Urinary interventions such as transurethral resection of the prostate were performed after brachytherapy in 5 of 12 patients with fistulas compared to 0 of 9 with ulcers alone. Argon plasma coagulation of the rectum for hematochezia was performed after brachytherapy in 3 of 12 patients with fistulas.Rates of post-brachytherapy rectal ulcers and fistulas are low as previously described. Post-brachytherapy interventions such as rectal biopsy, argon coagulation and urinary intervention may increase the risk of fistulas.

To compare biochemical failure using a prostate-specific antigen (PSA) threshold of0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL).Androgen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of0.2 ng/mL.Compared to nadir+2 ng/mL, the0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the0.2 ng/mL threshold (p 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319).Replacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.

Rates of late toxicity are higher for salvage treatment of local recurrence after prior radiotherapy. We present our experience with salvage prostate brachytherapy (BT) for local recurrence after definitive external beam radiotherapy with attention to the relationship between dose and late toxicity.From 2005 to 2012, 18 patients with biopsy proven locally recurrent prostate cancer and negative staging received low-dose-rate BT with a prescribed dose of 130-144 Gy. Toxicities were graded using Common Terminology Criteria for Adverse Events, version 3.0.Median followup is 31.5 months (range, 12-104). International Prostate Symptom Scores peaked at 3 months (median, 21/35), returning to baseline by 24 months. Urinary catheterization rate was 33% (median duration, 14 days; range, 1-90 days). Late Grade 3/4 genitourinary toxicity occurred in 1 patient each, one of whom also had Grade 3 late gastrointestinal toxicity; urethral strictures developed in three others. These 5 patients with late toxicity had higher dose to the prostate (isodose enclosing 90% [D90] median, 151 Gy; range, 135-185 Gy) compared with those without late complications (median, 134 Gy; range, 105-165; p0.04). Acute gastrointestinal toxicity Grade3 occurred in 44%. Four patients (22%) experienced biochemical failure.Salvage low-dose-rate prostate BT can provide durable biochemical control. Care should be taken to select patients with higher likelihood of organ-confined disease. The goal of planning should be to treat the recurrent disease to an adequate dose with careful attention to maintain a conservative D90.

PURPOSE To determine whether the use of 6 months' adjuvant androgen deprivation therapy (ADT) combined with brachytherapy for intermediate-risk (IR) and low-risk (LR) prostate cancer is associated with an increased risk of cardiovascular death. METHODS AND MATERIALS This is a retrospective analysis of prospectively collected data from men treated in the British Columbia Cancer Agency brachytherapy program from 1998 to 2012. Men were categorized by risk group and ADT use. Cardiac and other comorbidities were recorded and compared between groups. Biochemical control (Phoenix definition, nadir + 2 ng/mL) was ascertained. Overall, prostate, cardiac, and other-cause mortality were analyzed by the Kaplan-Meier method and Fine and Gray competing-risk analysis. RESULTS The study included 3155 men (1142 with LR cancer and 2013 with IR cancer) who have been followed up for a median of 7.9 years. ADT was received by 47% of IR patients and 37% of LR patients for a median of 6 months. Men with IR cancer were older and had more cardiac and other comorbidities than LR cases (P

Purpose To describe outcomes of men with unfavorable (high-tier) intermediate risk prostate cancer (H-IR) treated with low-dose-rate (LDR) brachytherapy, with or without 6 months of androgen deprivation therapy (ADT). Methods and Materials Patients with H-IR prostate cancer, treated before 2012 with LDR brachytherapy without external radiation are included. Baseline tumor characteristics are described. Outcomes between groups receiving ADT are measured by Phoenix (nadir +2 ng/mL), and threshold 0.4 ng/mL biochemical relapse definitions (bNEDs), as well as clinical end points. Standard descriptive and actuarial statistics are used. Results Two hundred sixty men were eligible, 139 (53%) did not receive ADT and 121 (47%) did. Median follow-up was 5 years. Men treated with ADT had higher T stage and percent positive cores but lower pathologic grade group. bNED rates with and without ADT at 5 years are 86% and 85% ( p = 0.52) with the Phoenix definition, and 83% and 78% ( p = 0.13) with the threshold definition. Local recurrence or metastasis were rare in both groups ( p = not significant). Death from prostate cancer only occurred in 4 patients, 2 in each group. Overall survival was 85% in those treated with ADT and 93% without at 8 years, p = 0.15. Conclusions The addition of 6 months of ADT to LDR brachytherapy for H-IR prostate cancer does not improve 5 year prostate specific antigen control, and we no longer routinely recommended it.

This study investigates whether Genomic Organization at Large Scales (which we propose to call GOALS) as quantified via nuclear phenotype characteristics and cell sociology features (describing cell organization within tissue) collected from prostate tissue microarrays (TMAs) can separate biochemical failure from biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of the 78 prostate cancer tissue cores collected from patients treated with RP, 16 who developed biochemical relapse (failure group) and 16 who were BNED patients (nonfailure group) were included in the analyses (36 cores from 32 patients). A section from this TMA was stained stoichiometrically for DNA using the Feulgen-Thionin methodology, and scanned with a Pannoramic MIDI scanner. Approximately 110 nuclear phenotypic features, predominately quantifying large scale DNA organization (GOALS), were extracted from each segmented nuclei. In addition, the centers of these segmented nuclei defined a Voronoi tessellation and subsequent architectural analysis. Prostate TMA core classification as biochemical failure or BNED after RP using GOALS features was conducted (a) based on cell type and cell position within the epithelium (all cells, all epithelial cells, epithelial2 cell layers away from basement membrane) from all cores, and (b) based on epithelial cells more than two cell layers from the basement membrane using a Classifier trained on Gleason 6, 8, 9 (16 cores) only and applied to a Test set consisting of the Gleason 7 cores (20 cores). Successful core classification as biochemical failure or BNED after RP by a linear classifier was 75% using all cells, 83% using all epithelial cells, and 86% using epithelial2 layers. Overall success of predicted classification by the linear Classifier of (b) was 87.5% using the Training Set and 80% using the Test Set. Overall success of predicted progression using Gleason score alone was 75% for Gleason7 as failures and 69% for Gleason6 as failures. © 2017 International Society for Advancement of Cytometry.

322 Background: Prospectively collected outcome data for 14,196 patients with localized prostate cancer treated with LDR brachytherapy (BT) from 7 institutions were analyzed. For the 80% of patients with a 4 year PSA < 0.2 ng/ml, 99% were free of clinical failure at 10 years and 96% at 15 years. We sought to validate this result with 2 independent data sets from mature prospective clinical trials. Methods: In the initial analysis, patients were treated with either BT alone (61%), or in combination with external beam radiotherapy (EBRT:8%), androgen deprivation (ADT:22%) or both (9%). 42% were low risk, 50% intermediate (IR) and 8% high risk(HR). KM analysis was carried out using clinical failure (local, distant, regional or biochemical triggering salvage) as endpoints for each of 4 PSA categories: PSA0.2 to < 0.5, PSA > 0.5 to < 1.0, and PSA>1.0 ng/ml. Results were compared to 12 year follow up data on a phase 2 trial of BT for IR prostate cancer (n=223; MDAnderson Cohort 1) and 10-year data from the BT arm of the phase 3 randomized ASCENDE RT trial (n=160, Cohort 2) for upper tier IR and HR prostate cancer. Results: The results of the initial KM analysis showed that for the 80% of patients with PSA < 0.2 ng/ml at 4 years, 99% were free of recurrence at 10 years (95% CI: 98.4-99.1) and 96% at 15 years (95% CI: 95-97). The association of treatment success with PSA range was highly significant (p