Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC. METHODS: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs. RESULTS: Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007). CONCLUSION: A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.

Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer.

BACKGROUND: We performed a secondary analysis of ACIS study to determine if synchronous versus metachronous metastatic presentation has any association with survival and treatment response to dual androgen receptor axis-targeted therapy (ARAT) in docetaxel naïve metastatic castrate resistant prostate cancer (mCRPC). METHODOLOGY: In this phase III randomized controlled trial, docetaxel naïve mCRPC patients were randomized to either apalutamide or placebo combined with abiraterone and prednisone. Multivariable Cox regression models were applied to determine the adjusted association of M-stage with radiographic progression-free survival (rPFS) and overall survival (OS). To determine the heterogeneity of treatment effect based on metastatic stage (M-stage) at presentation, Cox regression was applied with interaction terms between M-stage and treatment. RESULTS: Among 972 patients, 432 had M0, 334 had M1, while M-stage at presentation was unknown in 206. There was no association of M-stage at presentation with rPFS in patients with prior local therapy (LT) (hazard ratio for M1-stage: 1.22 [95% confidence interval: 0.82-1.82]; unknown: 1.03 [0.77-1.38]) or without prior LT (M1-stage: 0.87 [0.64-1.19]; unknown: 1.15 [0.77-1.72]) with no significant heterogeneity. Similarly, there was no association of M-stage with OS in patients with prior LT (M1-stage: 1.04 [0.81-1.33]; unknown: 0.98 [0.79-1.21]) or without prior LT (M1-stage: 0.95 [0.70-1.29]; unknown: 1.17 [0.80-1.71]) with no significant heterogeneity. Based on M-stage at presentation, we did not find any significant heterogeneity in treatment effect on rPFS (interaction p = 0.13), and OS (interaction p = 0.87). CONCLUSION: M-stage at presentation had no association with survival in chemotherapy-naïve mCRPC. We did not find any statistically significant heterogeneity in efficacy of dual ARAT based on synchronous versus metachronous presentation.

Association of PSA kinetics after testosterone recovery with subsequent recurrence: secondary analysis of a phase III randomized controlled trial.

PURPOSE: After cessation of androgen deprivation therapy (ADT), testosterone gradually recovers to supracastrate levels (> 50 ng/dL). After this, rises in prostate-specific antigen (PSA) are often seen. However, it remains unknown whether early PSA kinetics after testosterone recovery are associated with subsequent biochemical recurrence (BCR). METHODS: We performed a secondary analysis of a phase III randomized controlled trial in which newly diagnosed localized prostate cancer patients were randomly allocated to ADT for 6 months starting 4 months prior to or simultaneously with prostate RT. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after supracastrate testosterone recovery. Competing risk regression was used to evaluate the association of PSADT with relative incidence of BCR, considering deaths as competing events. RESULTS: Overall, 313 patients were eligible. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years from supracastrate testosterone recovery was 19% and 11% in patients with PSADT < 8 months and ≥ 8 months (p = 0.03). Compared to patients with PSADT of < 4 months, patients with higher PSADT (sHR for PSADT 4 to < 8 months: 0.36 [95% CI 0.16-0.82]; 8 to < 12 months: 0.26 [0.08-0.91]; ≥ 12 months: 0.20 [0.07-0.56]) had lower risk of relative incidence of BCR. CONCLUSIONS: Early PSA kinetics, within 18 months of recovery of testosterone to a supracastrate level, can predict for subsequent BCR. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit superior personalization of treatment.

Web-Based Asynchronous Tool to Facilitate Communication Between Primary Care Providers and Cancer Specialists: Pragmatic Randomized Controlled Trial.

BACKGROUND: Cancer poses a significant global health burden. With advances in screening and treatment, there are now a growing number of cancer survivors with complex needs, requiring the involvement of multiple health care providers. Previous studies have identified problems related to communication and care coordination between primary care providers (PCPs) and cancer specialists. OBJECTIVE: This study aimed to examine whether a web- and text-based asynchronous system (eOncoNote) could facilitate communication between PCPs and cancer specialists (oncologists and oncology nurses) to improve patient-reported continuity of care among patients receiving treatment or posttreatment survivorship care. METHODS: In this pragmatic randomized controlled trial, a total of 173 patients were randomly assigned to either the intervention group (eOncoNote plus usual methods of communication between PCPs and cancer specialists) or a control group (usual communication only), including 104 (60.1%) patients in the survivorship phase (breast and colorectal cancer) and 69 (39.9%) patients in the treatment phase (breast and prostate cancer). The primary outcome was patient-reported team and cross-boundary continuity (Nijmegen Continuity Questionnaire). Secondary outcome measures included the Generalized Anxiety Disorder Screener (GAD-7), Patient Health Questionnaire on Major Depression, and Picker Patient Experience Questionnaire. Patients completed the questionnaires at baseline and at 2 points following randomization. Patients in the treatment phase completed follow-up questionnaires at 1 month and at either 4 months (patients with prostate cancer) or 6 months following randomization (patients with breast cancer). Patients in the survivorship phase completed follow-up questionnaires at 6 months and at 12 months following randomization. RESULTS: The results did not show an intervention effect on the primary outcome of team and cross-boundary continuity of care or on the secondary outcomes of depression and patient experience with their health care. However, there was an intervention effect on anxiety. In the treatment phase, there was a statistically significant difference in the change score from baseline to the 1-month follow-up for GAD-7 (mean difference -2.3; P=.03). In the survivorship phase, there was a statistically significant difference in the change score for GAD-7 between baseline and the 6-month follow-up (mean difference -1.7; P=.03) and between baseline and the 12-month follow-up (mean difference -2.4; P=.004). CONCLUSIONS: PCPs' and cancer specialists' access to eOncoNote is not significantly associated with patient-reported continuity of care. However, PCPs' and cancer specialists' access to the eOncoNote intervention may be a factor in reducing patient anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT03333785; https://clinicaltrials.gov/ct2/show/NCT03333785.

5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

Cancer specialist perspectives on implementing an online communication system with primary care providers.

Context: The Canadian Team to Improve Community-Based Cancer Care along the Continuum (CanIMPACT) is a group of researchers, primary care providers (PCPs), cancer specialists, patients and caregivers working to improve cancer care coordination between PCPs and cancer specialists. Previous research by CanIMPACT and others has identified problems related to communication, coordination, and continuity of care. Objective: Describe findings from qualitative interviews with cancer specialists on implementation of an online communication system with PCPs. Study Design: Hybrid type I effectiveness-implementation study that included a qualitative research component and a pragmatic RCT. Setting: Ottawa Hospital Cancer Program and primary care practices in the Champlain region. Population Studied: Cancer specialists (nurses, medical and radiation oncologists, program administrators). Interviews conducted with 12 cancer specialists. Intervention: Cancer-specific adaptation of Champlain BASE™ eConsult, an online communication system for PCPs and cancer specialists called "eOncoNote". For patients receiving treatment for prostate or breast cancer, cancer specialists had an opportunity to participate in eOncoNote discussion with PCP for 4-6 months; for breast and colorectal cancer survivors, the eOncoNote discussion lasted for 1 year post discharge to the patient's PCP. Results: Cancer specialists described limited PCP involvement in cancer care while patients received active treatment, with one-way communication and notes being "sent into a vacuum". There was more communication with PCPs regarding patients with metastatic disease, comorbid conditions, after patients have completed treatment, or during palliative care. Patients and caregivers play a critical role in coordinating cancer care, helping to facilitate coordination. Lack of access to the same electronic medical record (EMR) among healthcare providers poses a barrier to cancer care coordination. eOncoNote had the potential to be useful tool but it was not used extensively. Conclusions: Accessing eOncoNote as a separate system was challenging to incorporate into the workflow, and cancer specialists highlighted the need for integration with their EMR. eOncoNote did not affect information sharing with PCPs, as there was limited uptake within primary care.

Transformation of Chlorofluorocarbons Investigated via Stable Carbon Compound-Specific Isotope Analysis.

Compound-specific isotope analysis (CSIA) is a valuable tool in contaminant remediation studies. Chlorofluorocarbons (CFCs) are ozone-depleting substances previously thought to be persistent in groundwater under most geochemical conditions but more recently have been found to (bio)transform in some laboratory experiments. To date, limited applications of CSIA to CFCs have been undertaken. Here, biotransformation-associated carbon isotope enrichment factors, εC,bulk for CFC-113 (εC,bulk = -8.5 ± 0.4‰) and CFC-11 (εC,bulk = -14.5 ± 1.9‰), were determined. δ13C signatures of pure-phase CFCs and hydrochlorofluorocarbons were measured to establish source signatures. These findings were applied to investigate potential in situ CFC transformation in groundwater at a field site, where carbon isotope fractionation of CFC-11 suggests naturally occurring biotransformation by indigenous microorganisms. The maximum extent of CFC-11 transformation is estimated to be up to 86% by an approximate calculation using the Rayleigh concept. CFC-113 δ13C values in contrast were not resolvably different from pure-phase sources measured to date, demonstrating that CSIA can aid in identifying which compounds may, or may not, be undergoing reactive processes at field sites. Science and public attention remains focused on CFCs, as unexplained source inputs to the atmosphere have been recently reported, and the potential for CFC biotransformation in surface and groundwaters remains unclear. This study proposes δ13C CSIA as a novel application to study the fate of CFCs in groundwater.

Nerve Grafting in Head and Neck Reconstruction.

In head and neck reconstructive surgery, especially of the mandible, the long-span processed nerve allograft (PNA) is a technological advancement that provides improved quality of life for patients who require ablative surgery by allowing for functional sensory recovery (FSR) in the majority of patients treated with immediate reconstruction. Recently published clinical prospective and retrospective multisite controlled cohort studies of immediate nerve reconstruction at the time of ablative surgery, including pediatric patient populations, were reviewed for valid and predictable outcomes of FSR following the reconstruction of the inferior alveolar nerve using > 5-cm PNA allografts. Both adult and pediatric patients demonstrate high percentages of FSR within 1 year. Pediatric patients demonstrate robust recovery with 100% reaching FSR within 1 year, whereas 89% of adults achieved FSR during the same time span; the pediatric patient population reached FSR earlier when compared with adults. Control, nonallograft nerve repair patients never achieved FSR, reaching only S2 levels in both adults and pediatric groups. There were no adverse events; in fact, no patients demonstrated the occurrence of neuropathic pain when the nerve repair was performed immediately in contrast to delayed repair states. Long-span (> 5-cm) nerve allografts provide FSR in pediatric patients and the majority of adult patients and should be used in patients who require ablation of the mandible for head and neck reconstruction.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline.

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Hypofractionated Radiotherapy for Localized Prostate Cancer: When and for Whom?

PURPOSE OF REVIEW: To summarize recent evidence concerning the use of moderately hypofractionated external beam radiotherapy, defined as 2.4-3.4 Gy per fraction, and ultrahypofractionated external beam radiotherapy (also known as stereotactic body radiotherapy [SBRT]), defined as at least 5 Gy per fraction, in men with localized prostate cancer. RECENT FINDINGS: Taken together, a number of recently completed randomized trials show that moderately hypofractionated radiotherapy confers similar biochemical control compared to conventionally fractionated radiotherapy without increasing late toxicity. These effects appear to extend across all baseline clinical risk groups. Several single-arm phase II studies, as well as a recently published large-scale randomized trial comparing SBRT with conventional fractionation, show very promising biochemical control and favorable acute and late treatment-related morbidity with the use of SBRT in predominantly low- and intermediate-risk prostate cancer. As it is associated with similar prostate cancer control and toxicity while improving patient convenience and reducing cost, moderate hypofractionation is a preferred alternative to conventional fractionation in a majority of men with localized prostate cancer choosing radiotherapy as their primary treatment modality. To date, studies conducted largely in low- and intermediate-risk prostate cancer report encouraging oncologic outcomes and acceptable toxicity with SBRT. Mature results of phase III trials evaluating five-fraction SBRT regimens are eagerly awaited.

Diagnostic accuracy of magnetic resonance imaging for tumour staging of bladder cancer: systematic review and meta-analysis.

The purpose of this study is to evaluate accuracy of magnetic resonance imaging (MRI) for local staging of bladder cancer for four clinical scenarios (T-stage thresholds) considered against current standards for clinical staging and secondarily to identify sources for variability in accuracy. Systematic review of patients with bladder cancer undergoing T-staging MRI to evaluate the diagnostic accuracy using bivariate random-effects meta-analysis. Sub-group analysis was done to explore variability; risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. The search identified 30 studies (5156 patients). Pooled accuracy at multiple T-stage thresholds: ≤T1 vs ≥T2 = sensitivity 87% (95% confidence interval [CI] 82-91), specificity 79% (95% CI 72-85); T-any vs T0 = sensitivity 65% (95% CI 23-92), specificity 90% (95% CI 83-94); ≤T2 vs ≥T3 = sensitivity 83% (95% CI 75-88), specificity 87% (95% CI 78-93); and

Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Bone health is a significant concern in men with prostate cancer. PURPOSE: To evaluate the effectiveness of drug, supplement, and lifestyle interventions aimed at preventing fracture, improving bone mineral density (BMD), or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer. DATA SOURCES: Ovid MEDLINE (1946 to 19 January 2017), EMBASE (1980 to 18 January 2017), and the Cochrane Database of Systematic Reviews (19 January 2017). STUDY SELECTION: Randomized trials and systematic reviews of trials that were published in English; involved men with nonmetastatic prostate cancer; and compared bone-targeted therapies with placebo, usual care, or other active treatments. DATA EXTRACTION: Two reviewers independently extracted study characteristics and assessed study risk of bias for each outcome. DATA SYNTHESIS: Two systematic reviews and 28 reports of 27 trials met inclusion criteria. All trials focused on men with nonmetastatic prostate cancer who were initiating or continuing androgen deprivation therapy (ADT). Bisphosphonates were effective in increasing BMD, but no trial was sufficiently powered to detect reduction in fractures. Denosumab improved BMD and reduced the incidence of new radiographic vertebral fractures in 1 high-quality trial. No trials compared calcium or vitamin D versus placebo. Three lifestyle intervention trials did not show a statistically significant difference in change in BMD between exercise and usual care. LIMITATIONS: Most trials were of moderate quality. Only 2 randomized controlled trials were designed to examine fracture outcomes. Potential harms of treatments were not evaluated. CONCLUSION: Both bisphosphonates and denosumab improve BMD in men with nonmetastatic prostate cancer who are receiving ADT. Denosumab also reduces risk for radiographic vertebral fractures, based on 1 trial. More trials studying fracture outcomes are needed in this population. PRIMARY FUNDING SOURCE: Program in Evidence-Based Care.

Sediment Monitored Natural Recovery Evidenced by Compound Specific Isotope Analysis and High-Resolution Pore Water Sampling.

Monitoring natural recovery of contaminated sediments requires the use of techniques that can provide definitive evidence of in situ contaminant degradation. In this study, a passive diffusion sampler, called "peeper", was combined with Compound Specific Isotope Analysis to determine benzene and monochlorobenzene (MCB) stable carbon isotope values at a fine vertical resolution (3 cm) across the sediment water interface at a contaminated site. Results indicated significant decrease in concentrations of MCB from the bottom to the top layers of the sediment over 25 cm, and a 3.5 ‰ enrichment in δ13C values of MCB over that distance. Benzene was always at lower concentrations than MCB, with consistently more depleted δ13C values than MCB. The redox conditions were dominated by iron reduction along most of the sediment profile. These results provide multiple lines of evidence for in situ reductive dechlorination of MCB to benzene. Stable isotope analysis of contaminants in pore water is a valuable method to demonstrate in situ natural recovery of contaminated sediments. This novel high-resolution approach is critical to deciphering the combined effects of parent contaminant (e.g., MCB) degradation and both production and simultaneous degradation of daughter products, especially benzene.

Radiation Therapy Summary of the AUA/ASTRO Guideline on Clinically Localized Prostate Cancer.

PURPOSE: Our purpose was to develop a summary of recommendations regarding the management of patients with clinically localized prostate cancer based on the American Urologic Association/ ASTRO Guideline on Clinically Localized Prostate Cancer. METHODS: The American Urologic Association and ASTRO convened a multidisciplinary, expert panel to develop recommendations based on a systematic literature review using an a priori defined consensus-building methodology. The topics covered were risk assessment, staging, risk-based management, principles of management including active surveillance, surgery, radiation, and follow-up after treatment. Presented are recommendations from the guideline most pertinent to radiation oncologists with an additional statement on health equity, diversity, and inclusion related to guideline panel composition and the topic of clinically localized prostate cancer. SUMMARY: Staging, risk assessment, and management options in prostate cancer have advanced over the last decade and significantly affect shared decision-making for treatment management. Current advancements and controversies discussed to guide staging, risk assessment, and treatment recommendations include the use of advanced imaging and tumor genomic profiling. An essential active surveillance strategy includes prostate-specific antigen monitoring and periodic digital rectal examination with changes triggering magnetic resonance imaging and possible biopsy thereafter and histologic progression or greater tumor volume prompting consideration of definitive local treatment. The panel recommends against routine use of adjuvant radiation therapy (RT) for patients with prostate cancer after prostatectomy with negative nodes and an undetectable prostate-specific antigen, while acknowledging that patients at highest risk of recurrence were relatively poorly represented in the 3 largest randomized trials comparing adjuvant RT to early salvage and that a role may exist for adjuvant RT in selected patients at highest risk. RT for clinically localized prostate cancer has evolved rapidly, with new trial results, therapeutic combinations, and technological advances. The recommendation of moderately hypofractionated RT has not changed, and the updated guideline incorporates a conditional recommendation for the use of ultrahypofractionated treatment. Health disparities and inequities exist in the management of clinically localized prostate cancer across the continuum of care that can influence guideline concordance.

Emergent radiotherapy for pelvic malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Patients with primary genitourinary (GU), gynecologic (GYN) and gastrointestinal (GI) cancers can develop life-threatening or critical function-threatening symptoms that necessitate emergent intervention with palliative radiotherapy (RT). Unfortunately, research describing the use of RT in this critical setting is lacking. We aimed to review literature describing emergent palliative RT for primary pelvic malignancies and provide a narrative synthesis of relevant studies. METHODS: A medical librarian searched Ovid MEDLINE, Embase Classic, and Embase databases for relevant English language references from 1946-2022. No restrictions were placed on study type, publication type or date. References for GU, GYN and GI cancers were grouped and synthesized separately. KEY CONTENT AND FINDINGS: The treatment of bleeding from primary pelvic tumors was the only indication for emergent RT identified, however, no references reported dedicated cohorts of patients treated for bleeding in the emergent setting. Most references were retrospective single institution studies describing various dose fractionation schemes for non-emergent palliative RT. Outcome measures and response assessment times varied. The latency to hemostasis after RT commencement was not well described; most studies reported outcomes captured weeks or months following treatment. In general, high rates of hemostasis for GU, GYN and GI tumors have been reported following RT schedules ranging from a single fraction to many weeks of fractionated treatments. Bleeding seems to respond more favorably than other symptoms including pain and obstruction. CONCLUSIONS: Managing bleeding was the only indication for emergent RT identified in our search. Scant data exist that describe the latency to a hemostatic response following RT. This is an important knowledge gap in the literature given how commonly patients are affected by this complication of primary pelvic malignancies.

Comparing the prevalence and association between anxiety, depression and gastrointestinal symptoms in gastroparesis versus functional dyspepsia: A systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence and associations between anxiety/depression, and gastrointestinal (GI) symptoms across gastroparesis and functional dyspepsia. METHODS: Twenty adult studies were identified through systematic searches of three databases (PubMed, CINAHL and PsycINFO) in September 2023. Meta-analysis was performed to estimate the pooled prevalence rates of anxiety and depression across gastroparesis and functional dyspepsia, and to determine whether the associations of anxiety/depression and gastrointestinal (GI) symptoms differ in gastroparesis versus functional dyspepsia. RESULTS: The overall pooled prevalence rate for anxiety was similar (χ2(1) = 2.45, p = .12) in gastroparesis (49%) and functional dyspepsia (29%). The overall pooled prevalence rate for depression in gastroparesis (39%), and functional dyspepsia (32%) was also similar (χ2(1) = 0.81, p = .37). No significant relationship between anxiety and GI symptoms (r = 0.11) or depression and GI symptoms (r = 0.16) was found in gastroparesis, whilst significant, though weak, positive relationships between anxiety and GI symptoms (r = 0.30) and depression and GI symptoms (r = 0.32) were found in functional dyspepsia. The association between GI symptoms and anxiety, but not depression, across gastroparesis and functional dyspepsia was found to be significant (χ2(1) = 5.22, p = .02). CONCLUSION: Contributing to ongoing debate as to whether gastroparesis and functional dyspepsia are interchangeable syndromes, this review found that anxiety and depression prevalence was similar in both conditions. Psychological assessment and the utilisation of effective and holistic care in both conditions is therefore warranted.

Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study.

PURPOSE: It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs). METHODS: We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa. We focused on 7 commonly prescribed classes of medications: metformin, statins, proton pump inhibitors (PPIs), cyclooxygenase 2 (COX-2) inhibitors, aspirin, acetaminophen, and NSAIDs (nonselective COX inhibitors). To account for multiple testing, a two-sided p < 0.0024 was set as the threshold for statistical significance. RESULTS: Overall, 1135 patients were eligible. There was some evidence of a differential treatment effect from abiraterone among patients who received concomitant NSAIDs (hazard ratio [HR] for OS: 0.54; 95% CI: 0.42-0.70) versus those who did not (HR: 0.74; 95% CI: 0.60-0.91), though this did not reach significance (interaction p = 0.05). A similar non-significant finding of heterogeneity of effect from abiraterone was noted among patients who received concomitant aspirin (HR for OS: 0.93 [0.63-1.36]) versus those who did not (HR: 0.61 [0.51-0.73]) (interaction p = 0.04). Receipt of NSAIDs was independently associated with a significantly inferior OS (HR: 1.37 [1.15-1.62]; p < 0.001) and higher relative incidence of PCSM (sHR: 1.47 [1.21-1.78]; p < 0.001). CONCLUSIONS: This exploratory analysis did not find statistically significant evidence of differences in treatment effects from ADT plus abiraterone in de novo high-risk mPCa based on the receipt of concurrent medications. The receipt of NSAIDs was independently associated with increased PCSM and inferior OS.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

BACKGROUND: As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario. METHODOLOGY:  Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death. RESULTS: We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7) or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period. CONCLUSIONS: We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on income or distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population.

Effect of Pelvic External Beam Radiation Therapy on Bone Mineral Density: A Secondary Analysis of a Phase 3 Randomized Controlled Trial.

PURPOSE: Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-masked, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT. METHODS AND MATERIALS: Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < -1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years. BMD was measured at baseline and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed-effects models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the 2 treatment arms. RESULTS: Among 1407 eligible patients, 31% (n = 447) received prior pelvic XRT. There was no significant difference in any clinical fractures among patients with (5.8%, 26 of 447) or without (5.2%, 50 of 960) prior pelvic XRT (P = .42). Prior pelvic XRT was associated with a significant (0.54%) improvement in BMD (95% CI, 0.05-1.02) in the placebo group and a nonsignificant (0.04%) decline in BMD (95% CI, -0.47 to -0.35) in the denosumab group (interaction P = .007). There was no significant difference in pelvic XRT effect on percent BMD change in the lumbar spine (P = .65) or total hip (P = .39) between the 2 treatment groups. CONCLUSIONS: We did not find sufficient evidence to suggest any detrimental effect of pelvic XRT on the treatment effect from denosumab on percent BMD change, with only an approximately 5% incidence of clinical fractures.