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

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

Systematic review of patient reported quality of life following stereotactic ablative radiotherapy for primary and metastatic liver cancer.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is a safe and effective modality in patients with liver cancer who are ineligible for other local therapies. However SABR is not current standard of practice and requires further validation. Patient reported quality of life (QOL) is key to this validation, yet no systematic reviews to date have been performed to analyse QOL following liver SABR. QOL is a critical part of therapy evaluation, particularly in disease states with short life expectancy. The purpose of this study was to conduct a systematic review of QOL outcomes for liver SABR. MATERIALS AND METHODS: MEDLINE and EMBASE databases from 1996 to October 2015 were queried to obtain English language studies analysing QOL following liver SABR. Included studies described patient-reported QOL as either a primary or secondary endpoint, and analysed QOL change over time. Studies were screened, and relevant data were abstracted and analysed. RESULTS: Of 2181 initially screened studies, 5 met all inclusion criteria. Extracted studies included a total of 392 eligible patients with hepatocellular carcinoma, liver metastases and intrahepatic cholangiocarcinoma. Four studies were prospective in design, and only one study was a conference abstract. Extracted studies were heterogeneous in dose prescription used (11-70 Gy in 3-30 fractions), in addition to reported QOL metrics (EORTC QLQ C-15 PAL,/C-30/LM-21, EuroQol 5D, FACT-Hep, FLIC) and final endpoints (range 6 weeks to 12 months). Despite this there were few statistically significant declines in QOL scores following SABR. Four studies demonstrated transient fatigue in the first 1-4 weeks, while 2 studies showed transient worsening of appetite at 1 month. In all but one instance (loss of appetite at 6 weeks), levels returned to insignificant difference baseline by the final endpoints. All studies showed no significant QOL decline in any domain at their respective endpoints. In studies with overlapping QOL tools, estimates of 3-month post SABR global QOL were similar. CONCLUSION: Results of this systematic review demonstrate well-preserved post liver SABR QOL. These findings strengthen the argument for liver SABR, and should aim to support future comparative effectiveness trials with other local modalities including surgery, chemoembolization and radiofrequency ablation, with a focus on QOL outcomes as an important endpoint.

Ablative Therapies in Metastatic Breast Cancer: A Systematic Review.

PURPOSE: Patients with oligometastatic breast cancer are being increasingly offered ablative therapies, yet it is unclear which subpopulations may derive long-term benefit. This study sought to explore factors that could define a clinically relevant oligometastatic breast cancer population that benefits from ablative therapies. METHODS: A systematic review using MEDLINE for English language articles published between 1985 and April 2014 was undertaken. Criteria for review included studies that reported overall survival (OS) or progression-free survival (PFS) in breast cancer patients with distant metastases which also: quantified the extent of disease, had metachronous presentation of metastases, and reported on at least 5 patients. RESULTS: Of 59 674 screened studies, 41 studies of 1813 individual patients were identified. All studies were observational cohort studies (level 2B or 4 evidence) and underwent critical review. All outcomes pertaining to OS and PFS were extracted. Extracted data were too heterogeneous to facilitate a meta-analysis. The only factor that suggested worse outcomes was positive margins post-metastasectomy. There was no clear signal for improved outcomes in regards to age, disease extent, disease-free interval, or receptor status. CONCLUSION: Existing evidence does not provide meaningful direction on which metastatic breast cancer patients should have ablation of their residual disease due to heterogeneous reporting of disease factors, patient factors, and outcomes. Thorough demonstration of the absence of high- or moderate-level evidence and the absence of clinical data to guide patient selection suggests that metastatic breast cancer patients being treated with ablative modalities should be placed on clinical trial.

Systemic therapy in men with metastatic castration-resistant prostate cancer:American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline.

PURPOSE: To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). METHODS: The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. RESULTS: When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 ((223)Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. RECOMMENDATIONS: Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or (223)Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to evaluate optimal sequences or combinations of therapies. Palliative care should be offered to all patients.

Screening high-risk populations for lung cancer: guideline recommendations.

INTRODUCTION: The aim of this practice guideline was to develop evidence-based recommendations for screening high-risk populations for lung cancer. METHODS: The guideline was developed using the methods of Cancer Care Ontario's Program in Evidence-Based Care. The core methodology of the Program in Evidence-Based Care's guideline development process is systematic review. A systematic review had recently been completed by a collaboration of the American Cancer Society, the American College of Chest Physicians, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. The evidence from that systematic review formed the basis of the recommendations, which were reviewed, and amended where necessary, by clinical experts in the fields of medical and radiation oncology, radiology, lung disease, and population health. RESULTS: The systematic review included eight randomized controlled trials and 13 single-arm studies evaluating screening with low-dose computed tomography (LDCT) in patients at risk for lung cancer. One large randomized trial reported a statistically significant reduction in lung cancer mortality with LDCT at 6 years compared with chest radiography. The practice guideline recommendations generally align with the parameters of the National Lung Screening Study. Deviations were described and justified by the guideline working group. The recommendations support screening persons at high-risk for lung cancer with advice for determining a positive result on LDCT, appropriate follow-up, and optimal screening interval. CONCLUSION: The benefits of screening high-risk populations for lung cancer with LDCT outweigh the harms if screening is implemented in a strictly controlled manner.

Intraspinal techniques for pain management in cancer patients: a systematic review.

PURPOSE: This systematic review outlines current evidence regarding the effectiveness of intraspinal techniques for cancer pain and addresses practical implementation issues. METHODS: A search of electronic databases identified systematic reviews and randomized controlled trials (RCTs) evaluating the effectiveness of intraspinal techniques in the setting of cancer pain. An environmental scan was completed via the internet to identify practice guidelines and resource documents addressing organizational and implementation issues in the delivery of intraspinal analgesia. Elements reviewed included patient selection, contraindications, monitoring, aftercare, follow-up, hospital discharge equipment, health personnel, patient education, and safety. MAIN RESULTS: Three systematic reviews, three consensus conferences, and 12 RCTs met the inclusion criteria for evidence of effectiveness. No single systematic review or consensus conference included all relevant RCTs or specifically addressed the use of intraspinal techniques for cancer pain. Six RCTs compared intraspinal techniques alone or combined with other interventions alone or in combination, four compared different intraspinal medications, and two compared different intraspinal techniques. In general, the evidence supported the use of intraspinal techniques for cancer pain management. The two main indications consistently identified were intractable pain not controlled by other conventional medical routes and/or side effects from conventional pain management strategies preventing dose escalation. Reports indicate intraspinal analgesia is equally or more effective than conventional medical management and often associated with fewer side effects. Thirteen resource documents addressed issues surrounding the delivery of intraspinal analgesia and program implementation. CONCLUSIONS: Intraspinal techniques monitored by an interprofessional health care team should be included as part of a comprehensive cancer pain management program.

Cumulative Index to Nursing and Allied Health Literature search strategies for identifying methodologically sound causation and prognosis studies.

We developed search strategies for detecting sound articles on causation and prognosis in Cumulative Index to Nursing and Allied Health Literature (CINAHL) in the year 2000. An analytic survey was conducted, comparing hand searches of 75 journals with retrievals from CINAHL for 5,020 search terms and 11,784 combinations for causation and 9,946 combinations for prognosis. For detecting sound causation studies, a three-term strategy maximized sensitivity at 97.0% with a specificity of 52.3%. For detecting sound prognosis studies, a three-term strategy maximized sensitivity at 92.2% with a specificity of 50.0%. These search filters will enhance the searching efforts of clinicians and researchers.

Age-specific search strategies for Medline.

BACKGROUND: Many clinicians and researchers are interested in patients of a specific age (childhood, geriatrics, and so on). Searching for age-specific publications in large bibliographic databases such as Medline is problematic because of inconsistencies in indexing, overlapping age categories, and the spread of the relevant literature over many journals. To our knowledge, no empirically tested age-specific search strategies exist for Medline. OBJECTIVE: We sought to determine the retrieval characteristics of age-specific terms in Medline for identifying studies relevant for five clinical specialties: adult medicine, geriatric medicine, pediatric medicine, neonatal medicine, and obstetrics. METHODS: We compared age-specific search terms and phrases for the retrieval of citations in Medline with a manual hand search of the literature for 161 core health care journals. Six experienced research assistants who were trained and intensively calibrated read all issues of 161 journals for the publishing year 2000. In addition to classifying all articles for purpose and quality, study participants' ages were also recorded. Outcome measures were sensitivity, specificity, precision, and accuracy of single and combination search terms. RESULTS: When maximizing sensitivity, the best sensitivity and specificity achieved with combination terms were 98% and 81.2%, respectively, for pediatric medicine, 96.4% and 55.9% for geriatric medicine, 95.3% and 83.6% for neonatal medicine, 94.9% and 64.5% for adult medicine, and 82% and 97.1% for obstetrics. When specificity was maximized, all disciplines had an expected decrease in sensitivity and an increase in precision. Highest values for optimizing best sensitivity and specificity were achieved in neonatal medicine, 92.5% and 92.6%, respectively. CONCLUSION: Selected single terms and combinations of MeSH terms and textwords can reliably retrieve age-specific studies cited in Medline.

Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus colonization.

BACKGROUND: Eradication strategies for methicillin-resistant Staphylococcus aureus (MRSA) are variable. We sought to summarize the evidence for use of antimicrobial agents to eradicate MRSA. OBJECTIVES: To describe the effects of topical and systemic antimicrobial agents on nasal and extra-nasal MRSA carriage, adverse events, and incidence of subsequent MRSA infections. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trials register (August 2003), the Cochrane Central Register of Controlled Trials (Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1988 to 2003), handsearched relevant literature, and contacted MRSA experts and the manufacturer of mupirocin. SELECTION CRITERIA: Randomized controlled trials of patients colonized with MRSA comparing topical or systemic antimicrobials to placebo or no treatment, and trials comparing various combinations of topical or systemic agents to no treatment, placebo, or to topical or systemic agents. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial methodological quality, and extracted data. Primary outcomes included eradication of MRSA, infection due to MRSA, and adverse events. MAIN RESULTS: Six trials (384 participants) met the inclusion criteria. No difference in MRSA eradication was detected in four studies: one that compared mupirocin to placebo, two that compared one systemic agent to no treatment (fusidic acid in one and rifampin or minocycline in the other) and one that compared mupirocin to topical fusidic acid and oral trimethoprim-sulfamethoxazole, examining nasal MRSA eradication as an outcome. One study compared minocycline to rifampin, with rifampicin being more effective in relation to eradication of MRSA from all sites at day 30 (relative risk 0.16; 95% confidence intervals 0.02 to 1.00), but the difference at 90 days was not statistically significant (n = 18). Two studies (one testing novobiocin and rifampin, the other ciprofloxacin and rifampin, versus trimethoprim-sulfamethoxazole and rifampin) did not demonstrate a difference in eradication of MRSA at all sites (n = 94). Adverse events with systemic agents occurred in up to 20% of participants, however reporting was sporadic and denominators small. All trials reported development of resistance to antimicrobial agents used. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support use of topical or systemic antimicrobial therapy for eradicating nasal or extra-nasal MRSA. There is no demonstrated superiority of either topical or systemic therapy, or of combinations of these agents. Potentially serious adverse events and development of antimicrobial resistance can result from therapy.

Interventions to prevent aspiration pneumonia in older adults: a systematic review.

A systematic review was conducted to assess the effectiveness of the following interventions for prevention of aspiration pneumonia (AP) in older adults: compensatory strategy/positioning changes, dietary interventions, pharmacologic therapies, oral hygiene, and tube feeding. Data sources included a key word search of the MEDLINE, EMBASE, Cochrane Library, CINAHL, and HealthSTAR databases and hand searches of six journals. Reference lists of relevant primary and review articles were searched. Studies included were randomized, controlled trials (RCTs) enrolling adults aged 65 and older at risk of and assessed for AP. Two investigators extracted data on population, intervention, outcomes, and methodological quality. Of the 17 identified RCTs, eight met the selection criteria, two addressed dietary management or compensatory swallowing, two assessed pharmacological therapies, one assessed oral hygiene, and three assessed tube feeding. None of the eight trials reported use of blinding, and allocation concealment was unclear in five. Use of amantadine prevented pneumonia in one trial of nursing home residents. The antithrombotic agent cilostazol prevented AP in another trial but resulted in excessive bleeding. Insufficient data exist to determine the effectiveness of positioning strategies, modified diets, oral hygiene, feeding tube placement, or delivery of food in preventing AP. Considering how common the problem of AP is in older adults, larger, high-quality RCTs on the effectiveness of preventive interventions are warranted.