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Introduction: The prevalence of hearing loss in Canada is high, with many patients requiring implantable hearing devices (IHDs) as treatment for their disease severity. Despite this need, many eligible patients do not pursue these interventions. The objective of this study was to examine rates of IHD based on geographic location to understand locoregional variation in access to care. Study Design: This was a retrospective population-based cohort study. Setting: All hospitals in the Canadian province of Ontario. Methods: Of all patients with IHD between April 1, 1992, and March 31, 2021, cochlear implants (CIs) (4,720) and bone-anchored hearing aids (BAHA) (1,125) cohorts were constructed. Place of residence was categorized based on Local Health Integrated Network (LHIN). Summary statistics for place of surgical institution based on LHIN at first surgery, name of institution of first surgery and "as the crow flies" distance (in km) between place of residence and surgical institution were calculated. Rate of implantations was calculated for LHIN regions based on number of surgeries per 1,000,000 persons/years. Results: Toronto Central, Central, Central East, and Champlain regions had >10% of patients undergoing BAHA and CI. 1,019 (90.6%) and 4,232 (89.7%) of patients receiving BAHA and CI, respectively, resided in urban/suburban regions and 94 patients (8.4%) and 436 (9.2%) resided in rural regions. The median distance between residential location and the institution was 46.4 km (interquartile range [IQR], 18.9–103.6) and 44.7 km (IQR, 15.7–96.9) for BAHA and CI, respectively. From 1992 to 2021, the number of CI and BAHA performed across Ontario increased by 17 folds and 6 folds, respectively. Conclusion: This large comprehensive population study provides longitudinal insight into the access to care of IHD based on geographic factors. Our findings of the present population-based study indicate an overall increase in access to devices with disproportionate access to care based on geographic locations. Further work is needed to characterize barriers to IHD access to align with demands. [ABSTRACT FROM AUTHOR]

Background and Aim: Cytomegalovirus (CMV) colitis is associated with negative outcomes in inflammatory bowel disease (IBD) and immunosuppressed cohorts and therefore requires timely recognition for appropriate management. We aimed to evaluate the diagnostic tools for CMV colitis and their associations with clinical outcomes. Methods: A retrospective cohort study of patients in a metropolitan health service with colonic samples analysed for CMV between 2012 and 2022, stratified into IBD and non‐IBD groups, was performed. The main outcome measures were the prevalence of positive and negative results for each CMV test, as well as need for colectomy, use of antiviral and hospital length of stay. Results: Five hundred eighty‐two biopsies from 418 patients were included; the median age was 36 years (interquartile range, 24–52 years) and 223 (53.3%) were men. Four hundred sixty‐one (79.2%) biopsies were from patients with IBD and 121 (20.8%) were from those without IBD. There were similar proportions of positive CMV histology (IBD 5.9% and non‐IBD 7.4%) and tissue CMV polymerase chain reaction (PCR) in the two groups (IBD 5.6% and non‐IBD 5.0%), but within each group, results were discordant. Positive CMV histology was significantly associated with need for colectomy in the IBD group, while positive tissue CMV PCR was not. Positive CMV histology, and tissue and serum CMV PCR were all significantly associated with antiviral use. Positive serum CMV PCR was significantly associated with colectomy. Conclusions: Histopathology remains the most predictive tool in assessing CMV colitis, while qualitative tissue CMV PCR was found to have limited utility. Quantitative serum CMV PCR may be useful but requires further evaluation. [ABSTRACT FROM AUTHOR]

Decipher is a genomic classifier (GC) prospectively validated postprostatectomy. We validated the performance of the GC in pretreatment biopsy samples within the context of 3 randomized phase 3 high-risk definitive radiation therapy trials. A prespecified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled in the NRG/Radiation Therapy Oncology Group (RTOG) 9202, 9413, and 9902 phase 3 randomized trials. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays and GC scores were obtained. The primary objective was to validate the independent prognostic ability for the GC for distant metastases (DM), and secondary for prostate cancer–specific mortality (PCSM) and overall survival (OS) with Cox univariable and multivariable analyses. GC scores were obtained on 385 samples, of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9-13). In the pooled cohort, on univariable analysis, the GC was shown to be a prognostic factor for DM (per 0.1 unit; subdistribution hazard ratio [sHR], 1.29; 95% confidence interval [CI], 1.18-1.41; P <.001), PCSM (sHR, 1.28; 95% CI, 1.16-1.41; P <.001), and OS (hazard ratio [HR], 1.16; 95% CI, 1.08-1.22; P <.001). On multivariable analyses, the GC (per 0.1 unit) was independently associated with DM (sHR, 1.22; 95% CI, 1.09-1.36), PCSM (sHR, 1.23; 95% CI, 1.09-1.39), and OS (HR, 1.12; 95% CI, 1.05-1.20) after adjusting for age, Prostate Specific Antigen, Gleason score, cT stage, trial, and randomized treatment arm. GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy, but the absolute improvement in outcome varied by GC risk. This is the first validation of a gene expression biomarker on pretreatment prostate cancer biopsy samples from prospective randomized trials and demonstrates an independent association of GC score with DM, PCSM, and OS. High-risk prostate cancer is a heterogeneous disease state, and GC can improve risk stratification to help personalize shared decision making. [ABSTRACT FROM AUTHOR]

Introduction: Hearing loss (HL) is considered a potentially modifiable risk factor for dementia. We aimed to examine the relationship between HL and incident dementia diagnosis in a province-wide population-based cohort study with matched controls. Methods: Administrative healthcare databases were linked to generate a cohort of patients who were aged ≥40 years at their first claimed hearing amplification devices (HAD) between April 2007 and March 2016 through the Assistive Devices Program (ADP) (257,285 with claims and 1,005,010 controls). The main outcome was incident dementia diagnosis, ascertained using validated algorithms. Dementia incidence was compared between cases and controls using Cox regression. Patient, disease, and other risk factors were examined. Results: Dementia incidence rates (per 1,000 person-years) were 19.51 (95% confidence interval [CI]: 19.26–19.77) and 14.15 (95% CI: 14.04–14.26) for the ADP claimants and matched controls, respectively. In adjusted analyses, risk of dementia was higher in ADP claimants compared with controls (hazard ratio [HR]: 1.10 [95% CI: 1.09–1.12, p < 0.001]). Subgroup analyses showed a dose-response gradient, with risk of dementia higher among patients with bilateral HADs (HR: 1.12 [95% CI: 1.10–1.14, p < 0.001]), and an exposure-response gradient, with increasing risk over time from April 2007-March 2010 (HR: 1.03 [95% CI: 1.01–1.06, p = 0.014]), April 2010-March 2013 (HR: 1.12 [95% CI: 1.09–1.15, p < 0.001]), and April 2013-March 2016 (HR: 1.19 [95% CI: 1.16–1.23, p < 0.001]). Conclusion: In this population-based study, adults with HL had an increased risk of being diagnosed with dementia. Given the implications of HL on dementia risk, understanding the effect of hearing interventions merits further investigation. [ABSTRACT FROM AUTHOR]

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: The 8th edition UICC/AJCC TNM8 (Tumour, Nodes, Metastasis) melanoma staging system introduced several modifications from the 7th edition (TNM7), resulting in changes in survival and subgroup composition. We set out to address the limited validation of TNM8 (stages I-IV) in large population-based datasets.Methods: This retrospective cohort-study included 6,414 patients from the population-based Ontario Cancer Registry diagnosed with cutaneous melanoma between January 1, 2007 and December 31, 2012. Kaplan-Meier curves estimated the melanoma-specific survival (MSS) and overall survival (OS). Cox proportional hazard models were used to estimate adjusted hazard ratios for MSS and OS across stage groups. The Schemper-Henderson measure was used to assess the variance explained in the Cox regression.Results: In our sample, 21.3% of patients were reclassified with TNM8 from TNM7; reclassifications in stage II were uncommon, and 44.1% of patients in stage III were reclassified to a higher subgroup. Minimal changes in MSS curves were observed between editions, but the stage IIB curve decreased and the stage IIIC curve increased. For TNM8, Stage I (n = 4,556), II (n = 1,206), III (n = 598), and IV (n = 54) had an estimated 5-year MSS of 98.4%, 82.5%, 66.4%, and 14.4%, respectively. Within stage III, IIIA 5-year MSS was 91.7% while stage IIID was 23.5%. HRs indicated that TNM8 more evenly separates subgroups once adjusted for patient- and disease-characteristics. The variance in MSS explained by TNM7 and TNM8 is 18.9% and 19.7%, respectively.Conclusion: TNM8 performed well in our sample, with more even separation of stage subgroups and a modest improvement in predictive ability compared to TNM7. [ABSTRACT FROM AUTHOR]

Background: Continuous quality improvement is important for cancer systems. However, collecting and compiling quality indicator data can be time-consuming and resource-intensive. Here we explore the utility and feasibility of linked routinely collected health data to capture key elements of quality of care for melanoma in a single-payer, universal health care setting. Method: This pilot study utilized a retrospective population-based cohort from a previously developed linked administrative data set, with a 65% random sample of all invasive cutaneous melanoma cases diagnosed 2007–2012 in the province of Ontario. Data from the Ontario Cancer Registry was utilized, supplemented with linked pathology report data from Cancer Care Ontario, and other linked administrative data describing health care utilization. Quality indicators identified through provincial guidelines and international consensus were evaluated for potential collection with administrative data and measured where possible. Results: A total of 7,654 cases of melanoma were evaluated. Ten of 25 (40%) candidate quality indicators were feasible to be collected with the available administrative data. Many indicators (8/25) could not be measured due to unavailable clinical information (e.g. width of clinical margins). Insufficient pathology information (6/25) or health structure information (1/25) were less common reasons. Reporting of recommended variables in pathology reports varied from 65.2% (satellitosis) to 99.6% (body location). For stage IB-II or T1b-T4a melanoma patients where SLNB should be discussed, approximately two-thirds met with a surgeon experienced in SLNB. Of patients undergoing full lymph node dissection, 76.2% had adequate evaluation of the basin. Conclusions: We found that use of linked administrative data sources is feasible for measurement of melanoma quality in some cases. In those cases, findings suggest opportunities for quality improvement. Consultation with surgeons offering SLNB was limited, and pathology report completeness was sub-optimal, but was prior to routine synoptic reporting. However, to measure more quality indicators, text-based data sources will require alternative approaches to manual collection such as natural language processing or standardized collection. We recommend development of robust data platforms to support continuous re-evaluation of melanoma quality indicators, with the goal of optimizing quality of care for melanoma patients on an ongoing basis. [ABSTRACT FROM AUTHOR]

Radiation therapy with androgen deprivation therapy (ADT) has historically been one of the mainstays of treatment for intermediate- and high-risk prostate cancer. The benefit of ADT likely derives from both enhancing local control and inhibiting micrometastatic disease. While level 1 evidence has demonstrated the benefits of 4-6 months of ADT for all men with intermediate-risk disease, further stratification of intermediate-risk prostate cancer into favorable and unfavorable subgroups indicates that ADT may not be necessary for favorable intermediate-risk disease but likely still provides a survival advantage for unfavorable intermediate-risk disease, even in the dose escalation era. Long-course ADT, consisting of 2-3 years of treatment, is the standard of care for high-risk prostate cancer managed with RT based on phase III trials. However, emerging data from a randomized trial raises the possibility that 18 months of ADT could be sufficient for select high-risk patients. The desire to minimize exposure to ADT lies in its many adverse effects, including the potential for cardiovascular harm in certain patients with significant coexisting comorbidity, possibly increased risk for neurocognitive and psychiatric events, and the well-documented metabolic changes. Providers need to carefully weigh these potential risks with the known survival benefits of ADT in aggressive localized and locally advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Literature regarding trends of incidence, mortality, and complications of acute exacerbation of chronic obstructive pulmonary disease (COPD) in the emergency departments (ED) is limited. What are trends of COPD exacerbation in ED? Data were obtained from the Nationwide Emergency Department Sample (NEDS) that constitutes a 20% sample of hospital-owned EDs and inpatient sample in the US. All ED encounters were included in the analysis. Complications of AECOPD were obtained by using ICD codes. Out of 1.082 billion ED encounters, 5,295,408 (mean age 63.31 ± 12.63 years, females 55%) presented with COPD exacerbation. Among these patients, 353,563(6.7%) had AECOPD-plus (features of pulmonary embolism, acute heart failure and/or pneumonia) while 4,941,845 (93.3%) had exacerbation without associated features or precipitating factors which we grouped as AECOPD. The AECOPD-plus group was associated with statistically significantly higher proportion of cardiovascular complications including AF (5.6% vs 3.5%; p < 0.001), VT/VF (0.14% vs 0.06%; p < 0.001), STEMI (0.22% vs 0.11%; p < 0.001) and NSTEMI (0.65% vs 0.2%; p < 0.001). The in-hospital mortality rates were greater in the AECOPD-plus population (0.7% vs 0.1%; p < 0.001). The incidence of both AECOPD and AECOPD-plus had worsened (p-trend 0.004 and 0.0003) and the trend of mortality had improved (p-trend 0.0055 and 0.003, respectively). The prevalence of smoking for among all COPD patients had increased (p-value 0.004), however, the prevalence trend of smoking among AECOPD groups was static over the years 2010–2018. There was an increasing trend of COPD exacerbation in conjunction with smoking; however, mortality trends improved significantly. Moreover, the rising burden of AECOPD would suggest improvement in diagnostics and policy making regarding management. [ABSTRACT FROM AUTHOR]

Ensuring high quality end of life (EOL) care is necessary for people with advanced non-small-cell lung cancer (NSCLC), given its high incidence, mortality and symptom burden. Aggressive EOL care can adversely affect the quality of life of NSCLC patients without providing meaningful oncologic benefit. Objectives: (1) To describe EOL health services quality indicators and timing of palliative care consultation provided to patients dying of NSCLC. (2) To examine associations between aggressive and supportive care and patient, disease and treatment characteristics. Methods: This retrospective population-based cohort study describes those who died of NSCLC in Ontario, Canada from 2009–2017. Socio-demographic, patient, disease and treatment characteristics as well as EOL health service quality and use of palliative care consultation were investigated. Multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. Results: Aggressive care quality indicators were present in 50.3% and supportive care indicators in 60.3% of the cohort (N = 37,203). Aggressive care indicators decreased between 2009 and 2017 (57.4% to 45.3%) and increased for supportive care (54.2% to 67.5%). Benchmarks were not met by 2017 in 3 of 4 cases. Male sex and greater comorbidity were associated with more aggressive EOL care and less supportive care. Older age was negatively associated and rurality positively associated with aggressive care. No palliative care consultation occurred in 56.0%. Conclusions: While improvements in the use of supportive rather than aggressive care were noted, established Canadian benchmarks were not met. Moreover, there is variation in EOL quality between groups and use of earlier palliative care must improve. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has been unprecedented and has led to drastic reductions in non-urgent medical visits. Deferral of these visits may have critical health impact, including delayed diagnosis for melanoma and other skin cancers. We examined the influence of the pandemic on skin biopsy rates in a large population-based cohort. Methods: Using a universal health care claims dataset from Ontario, we examined skin biopsies from January 6, 2020 to September 27, 2020, and compared these to the same period for 2019. Those diagnosed with anogenital cancers, younger than 20 years, residing out-of-province and with lapses in coverage were excluded. The sensitivity and specificity of claims diagnoses compared to a validated algorithm to identify keratinocyte carcinoma (KC), or to the cancer registry for melanoma was evaluated. Factors associated with biopsy during the early pandemic were investigated with modified Poisson regression. Results: A precipitous drop in total skin biopsies (15% of expected), biopsies for KC (18%) and melanoma (27%) was seen with the onset of COVID-19 cases (p<0.01). Claims diagnoses were of high specificity for KC (99%), and for melanoma (98%), though sensitivity was less (61%, 28% respectively). In adjusted analysis, the elderly (80+ years), females and residents of certain regions were less likely to be biopsied during the pandemic. Subsequently, there were substantial improvements in biopsy rates over 10 weeks. However, compared to 2019, a large backlog of expected cases still remained 28 weeks after lockdown (45,710 all biopsy, 9,104 KC, 595 melanoma). Interpretation: A drastic reduction in skin biopsies is noted early in the COVID-19 pandemic; this disproportionately affected the elderly, females and certain geographic regions. Though biopsies subsequently increased, a large backlog of cases remained after almost half a year. This will have implications for downstream care of skin cancer. Efforts should be made to limit diagnostic delay. [ABSTRACT FROM AUTHOR]

Arcobacter species are gram-negative rods that have been implicated in food- and waterborne illness. Although various cultural isolation methods have been proposed, the current procedures are unable to fully suppress the growth of background microbiota present in food samples, which inhibits Arcobacter isolation. The purpose of this study was to develop a selective enrichment broth and chromogenic plating medium to detect three Arcobacter species that have been recognized as emerging foodborne pathogens: Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii. The developed Nguyen- Restaino-Juárez (NRJ) Arcobacter detection system consists of a selective enrichment broth (NRJ-B) and a selective-differential plating medium (NRJ-M). The protocol of the detection method was determined by evaluating the growth of A. butzleri, A. cryaerophilus, and A. skirrowii under various temperatures (30, 35, and 428C) and incubation (aerobic, microaerophilic, and anaerobic) conditions. Additionally, 47 Arcobacter strains and 39 non-Arcobacter strains were tested in inclusivity and exclusivity evaluations of NRJ-B and NRJ-M. Overall, the study determined that the optimal growth conditions of Arcobacter species using the NRJ Arcobacter detection system were aerobic incubation at 308C. NRJ-B supported good growth of A. butzleri, A. cryaerophilus, and A. skirrowii while effectively suppressing the growth of non-Arcobacter strains after 48 h. Furthermore, NRJ-M yielded 97.8% inclusivity and 100.0% exclusivity using the tested strains and resulted in salmonpigmented Arcobacter colonies (1.0 to 1.5 mm in diameter) after 72 h. The novel protocol is the first to develop a chromogenic plating medium for the isolation of Arcobacter species. This simple and accurate test method would greatly contribute to understanding the distribution of pathogenic Arcobacter species in food samples. [ABSTRACT FROM AUTHOR]

PURPOSE: Trial economic analyses, such as cost-effectiveness analysis, often rely on trial-collected data, which are burdensome and expensive to collect and may be incomplete. In contrast, administrative databases systematically collect health system encounters. We investigated whether administrative data could improve the performance of cancer trial economic analysis. METHODS: Health administrative data were probabilistically linked to Ontario patient data from the Canadian Cancer Trials Group CO.17 trial (n = 572), which evaluated cetuximab plus best supportive care (75 linked Ontario patients) versus best supportive care alone (73 patients) in previously treated metastatic colorectal cancer. Trial-collected resource utilization data and vital status were compared with administrative data. Cost effectiveness in 2007 Canadian dollars was determined with bootstrap incremental cost-effectiveness ratio (ICER) CIs. RESULTS: Up to trial date of last contact, administrative data vital status was concordant in more than 96%. Twenty-nine subsequent deaths occurred. Up to trial last contact, there were 50 net additional hospitalizations in administrative data and 33 net additional emergency department visits. Total costs were $3,023,034 for the cetuximab group and $1,191,118 for the control group up to trial last contact. The ICER was $211,128 per life-year gained (90% CI, $101,396 to $694,950) up to trial last contact and $164,378 (90% CI, −$138,260 to $644,555) up to administrative data last contact. ICER estimates were similar to the analysis using trial-collected data. CONCLUSION: Administrative data were more complete than trial data for hospital encounters, a key cost driver in economic analysis. There was a longer follow-up. This demonstrates the potential of administrative data to relieve the burden of collecting key data in cancer trials, which represents a considerable effort and expense. [ABSTRACT FROM AUTHOR]

Background: Hypercoagulation is one of the striking features of COVID-19. Patients hospitalized with COVID-19 are at high risk for venous thromboembolism. However, it is unknown if the risk for venous thromboembolism persists after discharge. Case Summary: We report a case with pulmonary embolism 5 months after COVID-19. No risk factors for venous thrombosis have been identified. Conclusion: In COVID-19 related hospitalization, large studies are needed to identify the risk of venous thromboembolism after discharge. [ABSTRACT FROM AUTHOR]

Background: Hypercoagulation is one of the striking features of COVID-19. Patients hospitalized with COVID-19 are at high risk for venous thromboembolism. However, it is unknown if the risk for venous thromboembolism persists after discharge. Case Summary: We report a case with pulmonary embolism 5 months after COVID-19. No risk factors for venous thrombosis have been identified. Conclusion: In COVID-19 related hospitalization, large studies are needed to identify the risk of venous thromboembolism after discharge. [ABSTRACT FROM AUTHOR]

• ILC and Th17 cell populations are enriched at mucosal surfaces. • IL-17 and IL-22 are signature ILC3 and Th17 cytokines. • IL-17 and IL-22 are implicated in colorectal cancer progression. • The relative contribution of ILC and Th17-type cytokines to cancer needs to be defined. Innate lymphoid cells (ILCs) contribute to the regulation of gastrointestinal (GI) homeostasis. Over the past 15 years, there has been a large effort to dissect the mechanisms required for GI homeostasis, with a major focus on different immune cell populations and the cytokines that they produce. In contrast to T-helper (Th) cells, ILCs respond rapidly to cytokines in their microenvironment in the absence of specific antigens; however, once activated both cell populations have similar effector functions. Two effector cytokines produced by both ILC3 and Th17 cell populations, Interleukin (IL)-17 and IL-22, have taken center stage for their ability to signal directly to GI epithelial cells and promote epithelial cell survival. In this review, we outline our current understanding of ILCs in the GI tract, and focus on GI cancers associated with aberrant production of IL-17 and IL-22. We highlight evidence from both mouse and patient-based analyses and discuss how tumor cells may hijack the potential evolutionary redundancy of these two cell populations. [ABSTRACT FROM AUTHOR]

• Gastric cancer is a leading cause of cancer related deaths. • A common feature of gastric cancers is an inflammatory microenvironment. • Cytokines are produced in gastric tumours by a range of cell populations. • IL-17 and IL-18 associated cytokines may represent a new therapeutic opportunity. Chronic inflammation is recognized as a key tumor-promoting factor in a number of epithelial cancers, including gastric cancer (GC). The production of pro-inflammatory cytokines in the tumor microenvironment by both the innate and the adaptive immune response can activate signaling pathways that are associated with increased cell survival and proliferation of cancer cells. Among the cytokines that have most commonly been linked to inflammation-associated cancers, are the Th17 cell-associated cytokines IL-17A, IL-23, IL-22, and the IL-1 family members IL-1β and IL-18. However, whether their contribution to inflammation-associated cancers is universal, or specific to individual types of cancers, remains to be elucidated. This review will explore our current understanding of the known roles of these cytokines in gastritis and discuss how their therapeutic inhibition may be useful for GC. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-11 belongs to the IL-6 family of cytokines, discovered over 30 years ago. While early studies focused on the ability of IL-11 to stimulate megakaryocytopoiesis, the importance of this cytokine to inflammatory disease and cancers is only just beginning to be uncovered. This review outlines recent advances in our understanding of IL-11 biology, and highlights the development of novel therapeutics with the potential for clinical targeting of signaling by this cytokine in multiple diseases. [ABSTRACT FROM AUTHOR]

Abstract Purpose Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy. Methods Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir + 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were associated with metastasis and PCSM. Results The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5–9.7). Seventeen patients developed metastases, and five experienced PCSM. On multivariate analysis, PSA velocity ≥3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p < 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p < 0.001) were significantly associated with metastasis. PSA velocity ≥3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p = 0.012) on univariate analysis. Conclusions Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes. [ABSTRACT FROM AUTHOR]

Primary Objective: Closed brain injuries are a common danger in contact sports and motorized vehicular collisions. Mild closed brain injuries, such as concussions, are not easily visualized by computed imaging or scans. Having a comprehensive head/brain model and using fluid-structure interaction (FSI) simulations enable us to see the exact movement of the cerebrospinal fluid (CSF) under such conditions and to identify the areas of brain most affected. Research Design: The presented work is based on the first FSI model capable of simulating the interaction between the CSF flow and brain. Methods and Procedures: FSI analysis combining smoothed-particle hydrodynamics and high-order finite-element method is used. Main Outcomes and Results: The interaction between the CSF and brain under rapid acceleration and deceleration is demonstrated. The cushioning effect of the fluid and its effect on brain are shown. Conclusions: The capability to locate areas (down to the exact gyri and sulci) of the brain the most affected under given loading conditions, and therefore assess the possible damage to the brain and consequently predict the symptoms, is shown. [ABSTRACT FROM AUTHOR]

Background: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort.Methods: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis.Results: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis.Conclusions: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort. [ABSTRACT FROM AUTHOR]

Purpose: Although level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy.Methods and Materials: We identified 46,325 men in the National Cancer Database with a diagnosis of high-risk prostate cancer (Gleason score 8-10, clinical stage T3-T4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT from 2004 through 2011. Multivariable Cox regression analysis adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival.Results: The median follow-up period was 48.6 and 59.2 months for patients treated with EBRT only and combined modality RT, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort who underwent EBRT alone (adjusted hazard ratio 0.91, P=.001) but not for patients treated with combined modality RT (adjusted hazard ratio 1.05, P=.496), with a significant interaction (Pinteraction=.036).Conclusions: In contrast to the known survival benefit when ADT is given with EBRT, our results suggest that ADT might not improve survival for high-risk patients who undergo combined EBRT and brachytherapy. Given the significant adverse effects of ADT, in particular, with long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a noninferiority design should be undertaken. [ABSTRACT FROM AUTHOR]

Background Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP). Objective To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT). Design, setting, and participants Two hundred and thirty-five patients treated with either RP ( n = 105) or RT ± androgen deprivation therapy ( n = 130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers. The highest-grade core was sampled and Decipher was calculated based on a locked random forest model. Outcome measurements and statistical analysis Metastasis and PCSM were the primary and secondary outcomes of the study, respectively. Cox analysis and c-index were used to evaluate the performance of Decipher. Results and limitations With a median follow-up of 6 yr among censored patients, 34 patients developed metastases and 11 died of prostate cancer. On multivariable analysis, biopsy Decipher remained a significant predictor of metastasis (hazard ratio: 1.37 per 10% increase in score, 95% confidence interval [CI]: 1.06–1.78, p = 0.018) after adjusting for clinical variables. For predicting metastasis 5-yr post-biopsy, Cancer of the Prostate Risk Assessment score had a c-index of 0.60 (95% CI: 0.50–0.69), while Cancer of the Prostate Risk Assessment plus biopsy Decipher had a c-index of 0.71 (95% CI: 0.60–0.82). National Comprehensive Cancer Network risk group had a c-index of 0.66 (95% CI: 0.53–0.77), while National Comprehensive Cancer Network plus biopsy Decipher had a c-index of 0.74 (95% CI: 0.66–0.82). Biopsy Decipher was a significant predictor of PCSM (hazard ratio: 1.57 per 10% increase in score, 95% CI: 1.03–2.48, p = 0.037), with a 5-yr PCSM rate of 0%, 0%, and 9.4% for Decipher low, intermediate, and high, respectively. Conclusions Biopsy Decipher predicted metastasis and PCSM from diagnostic biopsy specimens of primarily intermediate- and high-risk men treated with first-line RT or RP. Patient summary Biopsy Decipher predicted metastasis and prostate cancer-specific mortality risk from diagnostic biopsy specimens. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that elderly patients might have age-specific genetic abnormalities yet be underrepresented in currently available sequencing repositories, which could limit the effect of sequencing efforts for this population.Methods and Materials: Leveraging The Cancer Genome Atlas (TCGA) data portal, 9 tumor types were analyzed. The frequency distribution of cancer by age was determined and compared with Surveillance, Epidemiology, and End Results data. Using the estimated median somatic mutational frequency of each tumor type, the samples needed beyond TCGA to detect a 10% mutational frequency were calculated. Microarray data from a separate prospective cohort were obtained from primary prostatectomy samples to determine whether elderly-specific transcriptomic alterations could be identified.Results: Of the 5236 TCGA samples, 73% were from patients aged <70 years. Comparing the distribution of TCGA samples by age to the Surveillance, Epidemiology, and End Results data, patients <70 years were well represented across most tumor types, but patients aged 80 to 99 years were underrepresented in all cancers (median TCGA underrepresentation of 167%). All cancers (except for colorectal) contained enough samples to detect a 10% mutational frequency in patients aged <60 years. In contrast, no cancer type had enough samples for which a 10% mutational frequency could be detected in patients aged ≥80 years. To further interrogate whether elderly patients with cancer were likely to harbor age-specific molecular abnormalities, we accessed transcriptomic data from a separate, larger database of >2000 prostate cancer samples. That analysis revealed significant differences in the expression of 10 genes in patients aged ≥70 years compared with those <70 years, of which 7 are involved in androgen signaling and/or DNA repair.Conclusions: Elderly patients have been underrepresented in genomic sequencing studies. Our data suggest the presence of elderly-specific molecular alterations. Further dedicated efforts to understand the biology of cancer among the elderly will be important moving forward. [ABSTRACT FROM AUTHOR]

Objectives: Prostate cancer is a common diagnosis with several treatment options for the newly diagnosed patient, including radiation, surgery, active surveillance, and watchful waiting. Although tailoring of treatment to individual patient needs is an important goal, the recent passage of the Affordable Care Act has placed renewed interest in cost containment and cost-effectiveness. We sought to conduct a literature review of recent US-based studies to analyze the cost-effectiveness of initial local treatments for localized prostate cancer.Methods: We conducted a systematic literature search through PubMed, the Cost-Effectiveness Analysis Registry, and manual cross-referencing of articles. We identified US-based studies with cost analyses starting in 2005 that studied the cost-effectiveness of initial local treatments for localized prostate cancer (surgery, radiation, or observation).Results: There were eight studies that met our inclusion and exclusion criteria. Most studies took the cost perspective of Medicare, and two studies also considered the societal cost in terms of lost patient time. Most studies also used a Markov model with inputs based on the available literature for the effectiveness and toxicity of the different treatment options. The radiation-focused studies tended to find brachytherapy (BT) or stereotactic body radiation therapy (SBRT) to be more cost-effective than intensity-modulated radiation therapy or proton beam therapy. These findings were primarily based on the lower cost of SBRT or BT with roughly equal efficacy and toxicity. The two studies focused on surgery found surgery to be more cost effective than intensity-modulated radiation therapy, at least for low-risk disease, and one study found BT to be more cost-effective than surgery, and watchful waiting to be the most cost-effective option overall.Conclusion: Cost-effectiveness analysis is important because it helps patients, physicians, and policymakers make quantitatively-based decisions, which balance treatment efficacy, toxicity, and costs. Significant methodological heterogeneity in the studies we found limit the ability to compare their results directly, but most found that for favorable-risk prostate cancer, shorter or simpler treatments tended to be more cost-effective, including no treatment (watchful waiting) in one study. [ABSTRACT FROM AUTHOR]

Purpose: The use of prostate brachytherapy has continued to decline in the United States. We examined the national practice patterns of both academic and nonacademic practices performing prostate brachytherapy by case volume per year to further characterize the decline and postulate the effect this trend might have on training the next generation of residents.Methods and Materials: Men diagnosed with prostate cancer who had undergone radiation therapy in 2004 to 2012 were identified. The annual brachytherapy case volume at each facility was determined and further categorized into ≤12 cases per year (ie, an average of ≤1 cases per month), 13 to 52 cases per year, and ≥53 cases per year (ie, an average of ≥1 cases per week) in academic practices versus nonacademic practices.Results: In 2004 to 2012, academic practices performing an average of ≤1 brachytherapy cases per month increased from 56.4% to 73.7%. In nonacademic practices, this percentage increased from 60.2% to 77.4% (P<.0001 for both). Practices performing an average of ≥1 cases per week decreased among both academic practices (from 6.7% to 1.5%) and nonacademic practices (from 4.5% to 2.7%).Conclusions: Both academic and nonacademic radiation oncology practices have demonstrated a significant reduction in the use of prostate brachytherapy from 2004 to 2012. With the case volume continuing to decline, it is unclear whether we are prepared to train the next generation of residents in this critical modality. [ABSTRACT FROM AUTHOR]

Purpose The Canadian Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized trial showed that brachytherapy boost reduces recurrence by 50% compared to dose-escalated radiation. We examined how men with identical inclusion criteria to the ASCENDE-RT trial were being treated in the United States. Methods and Materials We used the National Cancer Database to identify prostate cancer patients treated with radiation from 2004 through 2012 who met the inclusion criteria of the ASCENDE-RT trial (intermediate-/high-risk prostate cancer, excluding patients with prostate-specific antigen >40 or tumor stage T3b/T4). The Mantel–Haenszel test was used to investigate the trend for type of radiation modality used over the study period. Results A cohort of 156,411 patients was identified. Of those, 103,188 men (66%) were treated with external beam radiation therapy (EBRT) alone, 31,129 (20%) with brachytherapy alone, and 22,094 (14%) with EBRT plus brachytherapy. EBRT plus a brachytherapy boost demonstrated a significant decrease in utilization from 2004 to 2012 in both academic and nonacademic centers, declining from 15% to 8% in academic centers and from 19% to 11% in nonacademic centers ( p -Value for trend <0.0001 for both). Academic centers were significantly less likely to use brachytherapy boost than nonacademic centers (adjusted odds ratio: 0.68; 95% confidence interval: 0.66–0.70; p -Value: <0.0001). Conclusions Radiation oncology practices have demonstrated a significant reduction in the use of brachytherapy boost from 2004 to 2012, and the lowest utilization was in academic centers. In light of the superior results demonstrated for brachytherapy boost by the ASCENDE-RT trial, it is unclear whether academic centers are prepared to train the next generation of residents in this critical modality. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of recent relocation prior to a cancer diagnosis on cancer-specific outcomes.Methods: We identified 272,718 patients with two different entries in the Surveillance, Epidemiology, and End Results database within 3years of each other. Those who had relocated to a different county between entries were identified and we determined the risk of stage IV disease or cancer-specific mortality among relocators and non-relocators after adjusting for other patient-specific demographic and clinical factors.Results: A total of 4639 (1.7%) patients relocated to a new county within 3years prior to a second cancer diagnosis and 268,079 (98.3%) patients did not. Patients who had relocated to a new area were more likely to be diagnosed with stage IV cancer (25.2% vs. 20.8%; adjusted odds ratio=1.27; 95% confidence interval [CI], 1.18-1.37; P<0.001), and had an increased risk of 10-year cancer-specific mortality (20.9% vs. 17.9%; adjusted hazard ratio 1.26; 95% CI, 1.17-1.36; P<0.001).Conclusion: These results suggest that recent relocation to a new county prior to a cancer diagnosis is associated with an increased risk of late-stage presentation and worse cancer-specific mortality. [ABSTRACT FROM AUTHOR]

Our model of care recruited harm reduction staff to test for hepatitis C, and psychiatrists to prescribe DAAs, and resulted in high rates of treatment uptake. Keywords: care cascade; community treatment; hepatitis C; models of care; people who inject drugs EN care cascade community treatment hepatitis C models of care people who inject drugs 1763 1764 2 11/18/21 20211201 NES 211201 AUTHOR CONTRIBUTIONS AW has previously received funding from AbbVie for investigator-initiated research. Increasing points of access for hepatitis C testing by training healthcare workers, and creating interdisciplinary hepatitis C services by recruiting DAA prescribers that interface with priority populations, is critical to achieving health service equity. [Extracted from the article]

Background: We sought to determine whether patients with high-volume, low-risk prostate cancer are suitable candidates for ultrasound-guided brachytherapy, monotherapy alone, without supplemental external beam radiation.Materials and Methods: The study cohort comprised 200 consecutive patients who received ultrasound.guided monotherapy from November 02, 1998 to March 26, 2010. Real.time intraoperative treatment planning was performed for all patients. 145. Gy with I125 was prescribed to the prostate with no margin. The primary endpoint was time to prostate-specific antigen. (PSA) failure using the phoenix definition. Cox multivariable regression analysis was used to determine the factors significantly associated with time to PSA failure.Results: Median follow-up was 59 months (range 1.2-146.8 months). The median PSA was 5.0 ng/ml. For the overall cohort, both 5- and 8-year PSA failure-free survival was 92.3% (95% confidence interval [95% CI]: 86.5-95.7%). Low-risk patients per the NCCN criteria had 5- and 8-year PSA failure-free survival of 93.6%. On cox multivariable analysis, only baseline PSA (adjusted hazard ratio: 1.29 [95% CI: 1.02-1.65], P = 0.036) was associated with outcome. Among patients with Conclusions: Our analysis indicates that patients with a high number of cores positive for cancer can be adequately treated with modern brachytherapy as monotherapy and be spared the additional morbidity and cost of supplemental external beam radiation or androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Purpose A randomized trial recently found that adding brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical recurrence-free survival but not prostate cancer–specific mortality (PCSM). We investigated the relationship between BT boost and PCSM in a modern cohort from a large population-based database. Methods and Materials We conducted an analysis of patients in Surveillance, Epidemiology, and End Results diagnosed with intermediate- or high-risk prostate cancer in 2004–2011, treated with EBRT only or EBRT + BT. The cumulative incidence of PCSM was evaluated in the presence of other-cause mortality as a competing risk. Propensity score matching and multivariable Fine and Gray proportional hazard models were used to evaluate the association of combined modality RT on PCSM. Results A total of 52,535 patients were identified, of which 19.6% were treated with EBRT + BT. One-third of cases were high-risk. On multivariable analysis, the adjusted hazard ratio (AHR) of PCSM for EBRT + BT vs. EBRT alone was 0.69 (95% confidence interval [CI], 0.55–0.87, p = 0.002), and the adjusted incidence of PCSM was 1.8% vs. 2.7% at 8 years, respectively. In subgroup analyses, the AHR for PCSM was also significantly reduced with EBRT + BT for high-risk disease (AHR 0.70; 95% CI, 0.52–0.94, p = 0.02; adjusted incidence of PCSM at 8 years, 5.4% vs. 7.6%), but not for intermediate-risk disease. Conclusions BT boost was associated with a moderate reduction to PCSM in men with localized unfavorable-risk prostate cancer. Those most likely to benefit are younger patients with high-risk disease. [ABSTRACT FROM AUTHOR]

Objective To evaluate how a genomic classifier (GC) that predicts the risk of metastasis after prostatectomy would impact adjuvant treatment recommendations made by radiation oncologists and urologists. The 2 specialties often disagree about postprostatectomy adjuvant treatment recommendations. Materials and Methods Twenty-six radiation oncologists and 20 urologists with genitourinary oncology expertise reviewed de-identified clinical results from 11 patients after radical prostatectomy and made adjuvant treatment recommendations. The same cases were later randomized and reassigned, and treatment recommendations were made using the clinical information and GC test results together. Results Using clinical information alone, observation was recommended in 42% of decisions made by urologists vs 23% by radiation oncologists ( P < .0001). The GC test results altered 35% and 45% of treatment recommendations made by radiation oncologists and urologists, respectively. Multivariate analysis showed GC risk was the strongest factor influencing treatment recommendations by both specialties, with an adjusted odds ratio of 4.17 (95% confidence interval [CI], 2.26-7.70) and 6.51 (95% CI, 4.29-9.88) for radiation oncologists and urologists, respectively. GC results indicating high metastatic risk resulted in intensification of treatment, whereas low metastatic risk resulted in less aggressive recommendations. The GC results increased interdisciplinary agreement in treatment recommendations, as the odds of a recommendation for adjuvant treatment by urologists vs radiation oncologists increased from 0.27 (95% CI, 0.17-0.44) to 0.46 (95% CI, 0.29-0.75) after results of the GC test were available. Conclusion The GC test significantly influenced adjuvant postprostatectomy treatment recommendations, reduced disagreement between radiation oncologists and urologists, and has the potential to enhance personalization of postprostatectomy care. [ABSTRACT FROM AUTHOR]

Background: Racial disparities in cancer survival outcomes have been primarily attributed to underlying biologic mechanisms and the quality of cancer care received. Because prior literature shows little difference exists in the socioeconomic status of non-Hispanic whites and Asian Americans, any difference in cancer survival is less likely to be attributable to inequalities of care. We sought to examine differences in cancer-specific survival between whites and Asian Americans. Methods: The Surveillance, Epidemiology, and End Results Program was used to identify patients with lung (n = 130 852 [16.9%]), breast (n = 313 977 [40.4%]), prostate (n = 166 529 [21.4%]), or colorectal (n = 165 140 [21.3%]) cancer (the three leading causes of cancer-related mortality within each sex) diagnosed between 1991 and 2007. Fine and Gray's competing risks regression compared the cancer-specific mortality (CSM) of eight Asian American groups (Chinese, Filipino, Hawaiian/ Pacific Islander, Japanese, Korean, other Asian, South Asian [Indian/Pakistani], and Vietnamese) to non-Hispanic white patients. All P values were two-sided. Results: In competing risks regression, the receipt of definitive treatment was an independent predictor of CSM (hazard ratio [HR] = 0.37, 95% confidence interval [CI] = 0.35 to 0.40; HR = 0.55, 95% CI = 0.53 to 0.58; HR = 0.61, 95% CI = 0.60 to 0.62; and HR = 0.27, 95% CI = 0.25 to 0.29) for prostate, breast, lung, and colorectal cancers respectively, all P < .001). In adjusted analyses, most Asian subgroups (except Hawaiians and Koreans) had lower CSM relative to white patients, with hazard ratios ranging from 0.54 (95% CI = 0.38 to 0.78) to 0.88 (95% CI = 0.84 to 0.93) for Japanese patients with prostate and Chinese patients with lung cancer, respectively. Conclusions: Despite adjustment for potential confounders, including the receipt of definitive treatment and tumor characteristics, most Asian subgroups had better CSM than non-Hispanic white patients. These findings suggest that underlying genetic/biological differences, along with potential cultural variations, may impact survival in Asian American cancer patients. [ABSTRACT FROM AUTHOR]

Context Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition. Objective To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. Evidence acquisition The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. Evidence synthesis Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). Conclusions ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. Patient summary Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is lined by a single layer of epithelial cells that secrete mucus toward the lumen, which collectively separates the immune sentinels in the underlying lamina propria from the intestinal microflora to prevent aberrant immune responses. Inflammatory bowel disease (IBD) describes a group of autoimmune diseases that arise from defects in epithelial barrier function and, as a consequence, aberrant production of inflammatory cytokines. Among these, interleukin (IL)-6, IL-11, and IL-22 are elevated in human IBD patients and corresponding mouse models and, through activation of the JAK/STAT3 pathway, can both propagate and ameliorate disease. In particular, cytokine-mediated activation of STAT3 in the epithelial lining cells affords cellular protection, survival, and proliferation, thereby affording therapeutic opportunities for the prevention and treatment of colitis. In this review, we focus on recent insights gained from therapeutic modulation of the activities of IL-6, IL-11, and IL-22 in models of IBD and advocate a cautionary approach with these cytokines to minimize their tumor-promoting activities on neoplastic epithelium. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We sought to determine whether placing empty catheters within the prostate and then inverse planning iodine-125 seed locations within those catheters (High Dose Rate-Emulating Low Dose Rate Prostate Brachytherapy [HELP] technique) would improve concordance between planned and achieved dosimetry compared with a standard intraoperative technique. Methods and Materials: We examined 30 consecutive low dose rate prostate cases performed by standard intraoperative technique of planning followed by needle placement/seed deposition and compared them to 30 consecutive low dose rate prostate cases performed by the HELP technique. The primary endpoint was concordance between planned percentage of the clinical target volume that receives at least 100% of the prescribed dose/dose that covers 90% of the volume of the clinical target volume (V 100/D 90) and the actual V 100/D 90 achieved at Postoperative Day 1. Results: The HELP technique had superior concordance between the planned target dosimetry and what was actually achieved at Day 1 and Day 30. Specifically, target D 90 at Day 1 was on average 33.7 Gy less than planned for the standard intraoperative technique but was only 10.5 Gy less than planned for the HELP technique (p < 0.001). Day 30 values were 16.6 Gy less vs. 2.2 Gy more than planned, respectively (p = 0.028). Day 1 target V 100 was 6.3% less than planned with standard vs. 2.8% less for HELP (p < 0.001). There was no significant difference between the urethral and rectal concordance (all p > 0.05). Conclusions: Placing empty needles first and optimizing the plan to the known positions of the needles resulted in improved concordance between the planned and the achieved dosimetry to the target, possibly because of elimination of errors in needle placement. [Copyright &y& Elsevier]

Abstract: Purpose: To describe the use of a temporary spacer to reduce rectal dose prior to prostate radiation in a man with prior pelvic radiotherapy and review the relevant literature. Methods and Materials: A healthy 57-year-old man presented with high-risk prostate cancer (Gleason score of 8, prostate-specific antigen level [PSA] 12.6 ng/mL, T3a by magnetic resonance imaging [MRI]), only 2.5 years after a low anterior resection followed by pelvic chemo-radiotherapy to 50.4 Gy for a locally advanced rectal cancer. Due to the prior radiation, he was not felt to be a candidate for surgery or external beam radiation, so he chose long-term androgen deprivation therapy (ADT) plus high-dose-rate brachytherapy to 36 Gy in 6 fractions. To reduce the radiation dose to the anterior rectal wall, 10 mL of a polyethylene glycol hydrogel spacer was injected between the prostate and rectum and created between 1.4 and 1.5 cm of separation along the length of the prostate. Results: Two randomized trials demonstrating that local therapy plus ADT improves overall survival compared to ADT alone provided the rationale for additional prostate radiotherapy in this otherwise healthy patient. Salvage brachytherapy is associated with a 3.4% rate of rectal fistula among the 251 cases reported in the literature from 2000–2007, with rates as high as 12% in one series. The spacer allowed the rectal dose constraint goals to be easily met. Conclusions: Injecting an absorbable polyethylene glycol hydrogel to separate the prostate and rectum appears to be associated with decreased maximum and mean rectal doses, and may have particular utility in previously irradiated patients. [Copyright &y& Elsevier]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Treatment regret can have an adverse impact on a patient's overall outlook and has been associated with a poorer global quality of life. Understanding predictors of regret can help clinicians better counsel patients about their treatments so that later regret can be avoided. In previous studies, regret has been associated with lesser educational attainment, non-White race, greater post-treatment declines in sexual function and systemic symptoms. The present study found that, among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to regret their treatment choice than men without cardiovascular comorbidity. This study highlights the growing importance of considering comorbidity when counselling patients about prostate cancer treatment options, and provides a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer. OBJECTIVE To determine whether cardiovascular comorbidity is associated with increased treatment regret among men with recurrent prostate cancer., METHODS The study cohort comprised 795 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical recurrence at a median (interquartile range) of 5.5 (2.8-9.1) years after prostatectomy ( n= 410), external beam radiation therapy ( n= 237), brachytherapy ( n= 124) or primary androgen deprivation therapy ( n= 24)., Multivariable logistic regression analysis was used to determine whether cardiovascular comorbidity was associated with treatment regret., Cardiovascular comorbidity, which included myocardial infarction, congestive heart failure, angina, diabetes, stroke or circulation problems, was defined using a validated two-question screening process after adjusting for sociodemographic and treatment factors and post-treatment bladder and bowel toxicity., RESULTS Of 795 men, 14.8% reported regret., Men with cardiovascular comorbidity were more likely to experience post-therapy bowel toxicity ( P= 0.022)., In the adjusted multivariable model, the factors associated with increased treatment regret were: cardiovascular comorbidity (adjusted odds ratio [AOR]= 1.52 [95% CI:1.00-2.31], P= 0.048); younger age (AOR: 0.97 [95% CI 0.94-0.99] per year increase in age, P= 0.019); and bowel toxicity after treatment (AOR 1.58 [95% CI 1.03-2.43], P= 0.038)., CONCLUSIONS Among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to experience treatment regret than men without cardiovascular comorbidity., These data provide a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c–T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32–2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17–5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13–2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96–2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT. [ABSTRACT FROM AUTHOR]

The article presents a study on the association of androgen deprivation therapy (ADT) with cardiovascular death in prostate cancer patients. The researchers reviewed EMBASE and MEDLINE citations between January 1, 1966 and April 11, 2011 as well as the Cochrane Central Register of Controlled Trials database through April 11, 2011. They also used the Cochran Q statistic to assess the statistical heterogeneity among trials included in the meta-analysis. They found that ADT is associated with improved prostate cancer-specific survival and overall survival.

Purpose: To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and setup approaches employed in proton therapy. Methods: We used series of computed tomography data, which included the pretreatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription isodose were evaluated. Results: In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7–3.6 mm for individual patients, variations of >5 mm from the planning computed tomography observed in all series), and femur rotation angle (standard deviation between 1.3° and 4.8°, with the maximum excursion exceeding 10° in 6 of 10 datasets). Shifts in the position of treated volume (98% isodose) were correlated with the variations in the lateral tissue thickness. Conclusions: Analysis suggests that, combined with image-guided setup verification, the range compensator expansion technique prevents loss of dose to target from femur rotation and soft-tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background: In several human cancers, overexpression of Skp2 (S-phase kinase associated protein 2), which targets p27 for degradation, portends a poorer prognosis. We examined whether Skp2 overexpression is associated with recurrence following radical prostatectomy (RP) for prostate cancer. Methods: Immunohistochemical staining for Skp2, p27, and MIB-1 was performed on 109 men with node-negative prostate cancer surgically managed from 1985–1996. Associations between the stains were tested and Cox regression was used to determine the association between Skp2 expression and time to biochemical recurrence following RP. Results: The 12 tumors (11%) with Skp2 overexpression all had correspondingly low p27 expression (P = 0.006), and a similar inverse Skp2/p27 relationship was seen in vitro in LNCap cells. Skp2 overexpression in tissue was associated with higher Gleason score (P = 0.002), more advanced pathological stage (P = 0.01), and higher MIB-1 index (P = 0.03), but a more favorable PSA profile (P = 0.04). Five men received a TURP. Among 104 who received RP, median follow-up was 67 months (range: 0.2–218). After adjusting for PSA, pathologic stage, and Gleason score, Skp2 overexpression remained significantly associated with a shorter time to biochemical recurrence (adjusted hazard ratio 4.8 (95% C.I. 1.6–14, P = 0.004)). The median time to recurrence with high vs. low Skp2 was 4 vs. 54 months. Conclusions: Skp2 overexpression was seen in a significant minority of surgically-managed men and was independently associated with a higher risk of recurrence, raising the possibility that Skp2 could be useful as a prognostic biomarker and as a potential molecular target for novel systemic agents in prostate cancer. [Copyright &y& Elsevier]

Background: Brachytherapy for prostate cancer can be technically challenging in men with small prostates (≤20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. Methods and Materials: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray''s regression were used to determine whether volume ≤20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer–specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. Results: 443 patients (6.9%) had a prostate volume ≤20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06–4.79), volume ≤20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08–1.65], p = 0.0085) with 3-year estimates of ACM for ≤20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). Conclusion: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume ≤20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding. [Copyright &y& Elsevier]

BACKGROUND: A study was undertaken to determine the impact of prior coronary revascularization (angioplasty, stent, or coronary artery bypass graft) on the risk of all-cause mortality after neoadjuvant hormonal therapy (HT) for prostate cancer (PC) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (Ml). METHODS: Among 7839 men who received radiation with or without a median of 4 months of HT for PC from 1991 to 2006, 495 (6.3%) had CAD-induced CHF or Ml and formed the study cohort. Of these men, 250 (50.5%) had been revascularized before treatment for PC. Cox regression was used to determine whether HT increased the risk of all-cause mortality, and whether revascularization altered this risk, after adjusting for known PC prognostic factors and a propensity score for revascularization. RESULTS: Median follow-up was 4.1 years. Neoadjuvant HT was associated with an increased risk of all-cause mortality (28.9% vs 15.7% at 5 years; adjusted hazard ratio [HR], 1.73; 95% confidence interval [Cl], 1.13-2.64; P = .01). Men who received HT without revascularization had the highest risk of all-cause mortality (33.3%; adjusted HR, 1.48; 95% Cl, 1.01-2.18; P = .047), whereas men who were revascularized and did not receive HT had the lowest risk of all-cause mortality (9.4%; adjusted HR, 0.51; 95% Cl, 0.28-0.93; P = .028). The reference group had an intermediate risk of all-cause mortality (23.4%) and was comprised of men in whom HT use and revascularization were either both given or both withheld. CONCLUSIONS: In men with a history of CAD-induced CHF or Ml, neoadjuvant HT is associated with an excess risk of mortality, which appears to be reduced but not eliminated by prior revascularization. [ABSTRACT FROM AUTHOR]

Purpose: We examined whether rectal dose–volume histogram (DVH) parameters were associated with long-term patient-reported gastrointestinal (GI) quality of life (QOL) after conventional (70.2 GyE) or high-dose (79.2 GyE) radiation for prostate cancer. Methods and Materials: Of 64 men with localized prostate cancer alive with a minimum 7-year follow-up after treatment as part of a randomized trial with either 70.2 GyE or 79.2 GyE of external beam radiation at Massachusetts General Hospital, 56 men (88%) returned a QOL questionnaire, and 50 of those men had DVH information. The DVH parameters of the anterior rectal wall were correlated with patient-reported long-term GI QOL using Pearson correlation and t tests. Results: There was a trend toward an association between increased long-term GI dysfunction and higher V60 (p = 0.07), V65 (p = 0.06), V70 (p = 0.09), and V75 (p = 0.09). When dichotomized by their medians, a V60 > 54% (p = 0.04), V70 > 44% (p = 0.06), and V75 > 39% (p = 0.06) were associated with increased long-term GI dysfunction. There was no difference in long-term GI dysfunction between men on the conventional vs. high-dose arms (p = 0.49). Conclusions: Dose–volume histogram parameters of the anterior rectal wall were associated with long-term patient-reported GI QOL after prostate radiation, whereas the dose prescribed to the prostate was not, suggesting that DVH constraints, rather than total prescribed dose, may have the greatest impact on long-term bowel dysfunction, and therefore that continued dose escalation may be feasible if appropriate dose–volume constraints are met. [ABSTRACT FROM AUTHOR]