Feasibility of removable balloon implant for simultaneous magnetic nanoparticle heating and HDR brachytherapy of brain tumor resection cavities.

AIM: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant. METHODS: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated with temperature dependent brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to produce rapid heating (>0.2°C/s) of MNP-filled balloons in brain tissue-equivalent phantoms by absorbing 0.5 W/ml from a 5.7 kA/m field at 133 kHz. RESULTS: Simulated treatment plans demonstrate the ability to heat at-risk tissue around a brain tumor resection cavity between 40-48°C for 2-5cm diameter balloons. Experimental thermal dosimetry verifies the expected rapid and spherically symmetric heating of brain phantom around the MNP-filled balloon at a magnetic field strength that has proven safe in previous clinical studies. CONCLUSIONS: These preclinical results demonstrate the feasibility of using a TBT balloon to deliver heat simultaneously with HDR brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme.

Hyperthermia and immunotherapy: clinical opportunities.

Hyperthermia holds great promise to advance immunotherapy in the treatment of cancer. Multiple trials have demonstrated benefit with the addition of hyperthermia to radiation or chemotherapy in the treatment of wide-ranging malignancies. Similarly, pre-clinical studies have demonstrated the ability of hyperthermia to enhance each of the 8 steps in the cancer-immunotherapy cycle including stimulation of tumor-specific immunity. While there has been an extensive recent focus on augmenting immunotherapy with radiation, surprisingly to date, there have been no clinical trials assessing the combination of hyperthermia with immunotherapy. The study of hyperthermia with immunotherapy is particularly compelling when considered in the context of a new treatment paradigm for this anti-neoplastic modality. Novel concepts include ease of treatment including elicitation of the tumor-specific response of not requiring whole tumor heating, potentially shorter treatment time, better treatment tolerance as opposed to other multi-agent approaches to immunotherapy and the ability to apply heat repeatedly with immunotherapies, unlike ionizing radiation. Several questions remained with regard to clinical integration which can be readily addressed with thoughtful clinical trial design building upon lessons learned at the bench and from clinical trials combining radiation and immunotherapy. Examples of promising avenues for clinical investigation of hyperthermia and immunotherapy including melanoma, bladder, and head and neck cancers are reviewed. In summary, there is a present convergence of factors in oncology that compel further investigation of the integration of hyperthermia with immunotherapy for the benefit of cancer patients.

End-of-life care in an Australian acute hospital: a retrospective observational study.

BACKGROUND: There is a gap in knowledge about the kind and quality of care experienced by hospital patients at the end of their lives. AIMS: To document and compare the patterns in end-of-life care for patients dying across a range of different medical units in an acute care hospital. METHODS: A retrospective observational study of consecutive adult inpatient deaths between 1 July 2010 and 30 June 2014 in four different medical units of an Australian tertiary referral hospital was performed. Units were selected on the basis of highest inpatient death rates and included medical oncology, respiratory medicine, cardiology and gastroenterology/hepatology. RESULTS: Overall, 41% of patients died with active medical treatment plans, but significantly more respiratory and cardiology patients died with ongoing treatment (46 and 75% respectively) than medical oncology and gastroenterology patients (each 27%, P < 0.05). More medical oncology and gastroenterology patients were recognised as dying (92 and 88%) compared with 72% of respiratory and only 38% of cardiology patients (P < 0.001). Significantly, more medical oncology patients were referred to palliative care and received comfort care plans than all other patient groups. However, the rate of non-palliative interventions given in the final 48 h was not significantly different between all four groups. CONCLUSIONS: There were differences in managing the dying process between all disciplines. A possible solution to these discrepancies would be to create an integrated palliative care approach across the hospital. Improving and reducing interdisciplinary practice variations will allow more patients to have a high-quality and safe death in acute hospitals.

Long-term outcomes of partial prostate treatment with magnetic resonance imaging-guided brachytherapy for patients with favorable-risk prostate cancer.

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.

Decision Support and Shared Decision Making About Active Surveillance Versus Active Treatment Among Men Diagnosed with Low-Risk Prostate Cancer: a Pilot Study.

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.

Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: Results of NRG Oncology/RTOG study 0621.

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined. METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes. RESULTS: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy. CONCLUSIONS: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.

Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Sleep apnea prevalence in chronic kidney disease - association with total body water and symptoms.

BACKGROUND: Sleep apnea is common and associated with poor outcome in severe chronic kidney disease, but validated screening tools are not available. Our objectives were to determine the prevalence of sleep apnea in this population, to assess the validity of screening for sleep apnea using an ApneaLink device and to investigate the relationship of sleep apnea to; symptoms, spirometry and body water. METHODS: Patients with glomerular filtration rate ≤30 mL/min/1.73 m2, whether or not they were receiving haemodialysis, were eligible for enrolment. Participants completed symptom questionnaires, performed an ApneaLink recording and had total body water measured using bioimpedance. This was followed by a multi-channel polysomnography recording which is the gold-standard diagnostic test for sleep apnea. RESULTS: Fifty-seven participants were enrolled and had baseline data collected, of whom only 2 did not have sleep apnea. An apnea hypopnea index ≥30/h was found in 66% of haemodialysis and 54% of non-dialysis participants. A central apnea index ≥5/h was present in 11 patients, with only one dialysis patient having predominantly central sleep apnea. ApneaLink underestimated sleep apnea severity, particularly in the non-dialysis group. Neither total body water corrected for body size, spirometry, subjective sleepiness nor overall symptom scores were associated with sleep apnea severity. CONCLUSIONS: This study demonstrates a very high prevalence of severe sleep apnea in patients with chronic kidney disease. Sleep apnea severity was not associated with quality of life or sleepiness scores and was unrelated to total body water corrected for body size. Routine identification of sleep apnea with polysomnography rather than screening is more appropriate in this group due to the high prevalence.

The epidemiology of tuberculosis in the Australia Capital Territory, 2006-2015.

AIM: To review the epidemiology of tuberculosis (TB) in the Australian Capital Territory (ACT) over a 10 year period. Methods: A retrospective analysis of the ACT TB notification data from 1 January 2006 to 31 December 2015 was conducted. RESULTS: Over the 10 year study period there were 171 TB notifications in the ACT, with an increasing trend in the number of notifications over time. The median age of cases was 36 years (range 14 to 91 years) and 53.8% of cases were male. Most TB cases (84.2%) were born overseas. Among Australian-born cases the most common risk factor for acquiring TB was close/household contact with a known case of TB (30.8%). The most common risk factor in the overseas-born population was past travel or residence in a high-risk country (86.9%). Of all the TB cases notified, 82.4% successfully completed treatment. CONCLUSION: There was an increasing trend in the number of TB notifications in the ACT over the study period. The highest rate of TB notifications remained in the overseas-born population; with other studies suggesting this is commonly due to reactivation of latent tuberculosis infection (LTBI). As Australia starts working towards TB elimination, options for the screening and management of LTBI, especially in high risk populations, need to be explored.

Focused ultrasound for treatment of bone tumours.

PURPOSE: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. METHODS: A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. RESULTS: Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastatic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. CONCLUSIONS: Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours.

International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions.

Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

The quality frontier.

Quality is gaining increased attention in medicine including oncology. This heightened focus on quality is long overdue, as noted by the Institute of Medicine over a decade ago. Unfortunately, medical practice including the numerous disciplines of oncology continues to fall short of its 'quality frontier', an analogous concept to the productivity frontier in business. Diverse but inter-related forces including culture, transparency, personalized medicine, economics and informatics are together driving the practice of oncology closer to its quality frontier. Examples of initial progress in relation to each of these forces are reviewed and their implications for future impact on quality discussed.

A paradigm shift from anatomic to functional and molecular imaging in the detection of recurrent prostate cancer.

Approximately a third of men with localized prostate cancer who are treated with external beam radiation therapy (EBRT) or radical prostatectomy (RP) develop biochemical failure (BF). Presumably, BF will progress to distant metastasis and prostate cancer-specific mortality in some patients over subsequent years. Accurate detection of recurrent disease is important because it allows for appropriate treatment selection (e.g., local vs systemic therapy) and early delivery of therapy (e.g., salvage EBRT), which affect patient outcome. In this article, we discuss the paradigm shift in imaging technology in the detection of recurrent prostate cancer. First, we discuss the commonly used morphological and anatomical imaging modalities and their role in the post-RP and post-EBRT settings of BF. Second, we discuss the accuracy of functional and molecular imaging techniques, many of which are under investigation. Further studies are needed to establish the role of imaging techniques for detection of cancer recurrence and clinical decision-making.

Components of a hyperthermia clinic: recommendations for staffing, equipment, and treatment monitoring.

Like other technically sophisticated medical endeavours, a hyperthermia clinic relies on skilled staffing. Physicians, physicists and technologists perform multiple tasks to ensure properly functioning equipment, appropriate patient selection, and to plan and administer this treatment. This paper reviews the competencies and tasks that are used in a hyperthermia clinic.

Predictors of Interest in Radiation Oncology: The Effect of Race, Ethnicity, Gender, and Other Diversity Measures.

Purpose: The presence of women and people underrepresented in medicine (URiM) continues to be lower in radiation oncology (RO) than within the United States population, medical school graduates, and oncology fellowship applicants. The objective of this study was to identify demographics of matriculating medical students who are inclined to consider pursuing a residency in RO and identify barriers to entry that students may perceive before medical school training. Methods and Materials: A survey of incoming medical students at New York Medical College was distributed via e-mail and assessed demographic background information, interest in and awareness of oncologic subspecialties, and perceived barriers to RO. Results: Students of the incoming class of 2026 had a complete response rate of 72% (155 complete responses and 8 incomplete responses of 214 class members). Two-thirds of participants had prior awareness of RO, and half have considered pursuing an oncologic subspecialty, but less than one-fourth have ever previously considered a career in RO. Students responded that they need more education, clinical exposure, and mentorship to increase their chance of choosing RO. Male participants had 3.4 times the odds of having an acquaintance in the community tell them about the specialty and also had significantly greater interest in using advanced technologies. There were no URiM participants who had personal relationships with an RO physician compared with 6 (4.5%) non-URiM participants. The average response to "What is the likelihood that you will pursue a career in RO?" showed no significant difference between genders. Conclusions: All races and ethnicities scored a similar likelihood of pursuing a career in RO, which differs greatly from the current RO workforce. Responses emphasized the importance of education, mentorship, and exposure to RO. This study demonstrates the need for support of female and URiM students during medical school.

ACR-ARS Practice Parameter on Informed Consent Radiation Oncology.

OBJECTIVES: Consent is a communication process between the patient and a health care provider, in which both parties have the opportunity to ask questions and exchange information relevant to the patient's diagnosis and treatment. The process of informed consent is designed to protect a patient's autonomy in their medical decision-making in the context of an asymmetric relationship with the health care system. A proper consent process assures a patient's individual autonomy, reduces the opportunity for abusive conduct or conflicts of interest, and raises trust levels among participants. This document was developed as an educational tool to facilitate these goals. METHODS: This practice parameter was produced according to the process described under the heading "The Process for Developing ACR Practice Parameters and Technical Standards" on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Committee members were charged with reviewing the prior version of the informed consent practice parameter published in 2017 and recommending additions, modifications, or deletions. The committee met through remote access and subsequently through an online exchange to facilitate the development of the revised document. Focus was given on identifying new considerations and challenges with informed consent given the evolution of the practice of radiation oncology in part driven by the COVID-19 pandemic and other external factors. RESULTS: A review of the practice parameter published in 2017 confirmed the ongoing relevance of recommendations made at that time. In addition, the evolution of the practice of radiation oncology since the publication of the prior document resulted in the need for new topics to be addressed. These topics include remote consent either through telehealth or telephone and with the patient or their health care proxy. CONCLUSIONS: Informed consent is an essential process in the care of radiation oncology patients. This practice parameter serves as an educational tool designed to assist practitioners in optimizing this process for the benefit of all involved parties.

Evaluation of a Balloon Implant for Simultaneous Magnetic Nanoparticle Hyperthermia and High-Dose-Rate Brachytherapy of Brain Tumor Resection Cavities.

Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs energy, thereby generating heat, while an HDR source travels to the center of the balloon via a catheter to deliver the radiation dose. A 3D-printed human skull model was filled with brain-tissue-equivalent gel for in-phantom heating and radiation measurements around four 3 cm balloons. For the in vivo experiments, a 1 cm diameter balloon was surgically implanted in the brains of three living pigs (40-50 kg). The durability and robustness of TBT balloon implants, as well as the compatibility of their heat and radiation delivery components, were demonstrated in laboratory studies. The presence of the nanofluid, magnetic field, and heating up to 77 °C did not affect the radiation dose significantly. Thermal mapping and 2D infrared images demonstrated spherically symmetric heating in phantom as well as in brain tissue. In vivo pig experiments showed the ability to heat well-perfused brain tissue to hyperthermic levels (≥40 °C) at a 5 mm distance from the 60 °C balloon surface.

Updated results of magnetic resonance imaging guided partial prostate brachytherapy for favorable risk prostate cancer: implications for focal therapy.

PURPOSE: We report updated results of magnetic resonance imaging guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy. MATERIALS AND METHODS: From 1997 to 2007, 318 men with cT1c, prostate specific antigen less than 15 ng/ml, Gleason 3 + 4 or less prostate cancer received magnetic resonance imaging guided brachytherapy in which only the peripheral zone was targeted. To exclude benign prostate specific antigen increases due to prostatic hyperplasia, we investigated the usefulness of defining prostate specific antigen failure as nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. Cox regression was used to determine the factors associated with prostate specific antigen failure. RESULTS: Median followup was 5.1 years (maximum 12.1). While 36 patients met the nadir +2 criteria, 16 of 17 biopsy proven local recurrences were among the 26 men who also had a prostate specific antigen velocity greater than 0.75 ng/ml per year (16 of 26 vs 1 of 10, p = 0.008). Using the nadir +2 definition, prostate specific antigen failure-free survival for low risk cases at 5 and 8 years was 95.1% (91.0-97.3) and 80.4% (70.7-87.1), respectively. This rate improved to 95.6% (91.6-97.7) and 90.0% (82.6-94.3) using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. For intermediate risk cases survival was 73.0% (55.0-84.8) at 5 years and 66.4% (44.8-81.1) at 8 years (the same values as using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year). CONCLUSIONS: Requiring a prostate specific antigen velocity greater than 0.75 ng/ml per year in addition to nadir +2 appears to better predict clinical failure after therapies that target less than the whole gland. Further followup will determine whether magnetic resonance imaging guided brachytherapy targeting the peripheral zone produces comparable cancer control to whole gland treatment in men with low risk disease. However, at this time it does not appear adequate for men with even favorable intermediate risk disease.

Anticholinergic therapy for acute asthma in children.

BACKGROUND: Inhaled anticholinergics as single agent bronchodilators (or in combination with beta(2)-agonists) are one of the several medications available for the treatment of acute asthma in children. OBJECTIVES: To determine the effectiveness of only inhaled anticholinergic drugs (i.e. administered alone), compared to a control in children over the age of two years with acute asthma. SEARCH METHODS: The Cochrane Register of Controlled Trials (CENTRAL), and the Cochrane Airways Group Register of trials were searched by the Cochrane Airways Group. The latest search was performed in April 2011. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in which inhaled anticholinergics were given as single therapy and compared with placebo or any other drug or drug combinations for children over the age of two years with acute asthma. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data and assessed trial quality. MAIN RESULTS: Six studies met the inclusion criteria but were limited by small sample sizes, various treatment regimes used and outcomes assessed. The studies were overall of unclear quality. Data could only be pooled for the outcomes of treatment failure and hospitalisation. Other data could not be combined due to divergent outcome measurements. Meta-analysis revealed that children who received anticholinergics alone were significantly more likely to have treatment failure compared to those who received beta(2)-agonists from four trials on 171 children (odds ratio (OR) 2.27; 95% CI 1.08 to 4.75). Also, treatment failure on anticholinergics alone was more likely than when anticholinergics were combined with beta(2)-agonists from four trials on 173 children (OR 2.65; 95% CI 1.2 to 5.88). Data on clinical scores/symptoms that were measured on different scales were conflicting. Individual trials reported that lung function was superior in the combination group when compared with anticholinergic agents used alone. The use of anticholinergics was not found to be associated with significant side effects. AUTHORS' CONCLUSIONS: In children over the age of two years with acute asthma exacerbations, inhaled anticholinergics as single agent bronchodilators were less efficacious than beta(2)-agonists. Inhaled anticholinergics were also less efficacious than inhaled anticholinergics combined with beta(2)-agonists. Inhaled anticholinergic drugs alone are not appropriate for use as a single agent in children with acute asthma exacerbations.