Cindy Walker-Dilks

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.

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.

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

PurposeThis systematic review outlines current evidence regarding the effectiveness of intraspinal techniques for cancer pain and addresses practical implementation issues.MethodsA 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 resultsThree 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.ConclusionsIntraspinal techniques monitored by an interprofessional health care team should be included as part of a comprehensive cancer pain management program.

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.

Systemic Therapy in Men with Metastatic Castration-resistant Prostate Cancer: A Systematic Review

AIMS Since 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC. MATERIALS AND METHODS Searches were carried out in MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. Eligible articles included RCTs comparing systemic therapy or combination (excluding primary or secondary androgen deprivation therapy, bone protective agents or radionuclides) with placebo or other agents in men with mCRPC. RESULTS Twenty-five RCTs met the selection criteria. In chemotherapy-naive patients, targeted therapy with tasquinimod conferred a benefit in progression-free survival. Immunotherapy with sipuleucel-T extended overall survival and was well tolerated, but had no effect on the time to disease progression. Hypercastration with abiraterone extended progression-free survival, whereas overall survival was improved but not statistically proven. In the chemotherapy setting, updated and new trials of docetaxel alone confirmed the survival benefit seen in previous studies. A survival benefit with the addition of estramustine to docetaxel shown in a previous study did not lead to an improvement in pain palliation or quality of life. Trials of combining targeted therapies with docetaxel generally did not extend survival. The addition of bevacizumab improved progression-free survival, but not overall survival. The addition of GVAX immunotherapy or calcitriol was harmful. In the post-chemotherapy setting, progression-free and overall survival benefits were detected with cabazitaxel, abiraterone and enzalutamide. Cabazitaxel was associated with greater toxicity, whereas abiraterone and enzalutamide had less severe adverse effects. Satraplatin and sunitinib both extended progression-free survival, but did not improve overall survival. CONCLUSION Docetaxel-based chemotherapy remains the standard of care in men with mCRPC who are candidates for palliative systemic therapy. Promising results are emerging with sipuleucel-T and abiraterone in the pre-docetaxel setting and cabazitaxel, abiraterone and enzalutamide in patients who progress on or after docetaxel. Further research to determine the optimal choice, sequence or even the combination of these agents is necessary.

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.

Contribution of the Cochrane Library to the evidence-based journals.

Systematic reviews, particularly those published in the Cochrane Library , now form a substantial part of the content of ACP Journal Club , Evidence-Based Medicine , Evidence-Based Nursing , and Evidence-Based Mental Health . This contribution has grown steadily since the first publication of the Cochrane Library . What makes the systematic reviews published in the Cochrane Library so amenable to the evidence-based journals? Up to the end of 2002, 4 evidence-based abstract journals were produced by the Health Information Research Unit (HIRU) at McMaster University in Hamilton, Ontario, Canada. The first was ACP J Club , begun in 1991. Published bimonthly by the American College of Physicians (ACP), each issue contains 25 research abstracts with clinical commentaries on internal medicine topics. Evidence-Based Medicine , published bimonthly by the BMJ Publishing Group starting in …

How to search for and find evidence about therapy

Health professionals need to keep up with generic advances in medicine and to track down valid evidence with which to solve specific patient problems. Various tools exist for helping clinicians with the task of keeping current, and Evidence-Based Medicine is one of them. It often will not include, however, evidence for solving the specific patient problem you are facing today. Accordingly, this EBM Note is the first of a set that will show you how to effectively and efficiently search for and find ready-for-clinical-application evidence from the medical literature. It will help you find the best evidence about therapy.

Bone Health and Bone-targeted Therapies for Prostate Cancer: a Programme in Evidence-based Care — Cancer Care Ontario Clinical Practice Guideline

AIMS To make recommendations with respect to bone health and bone-targeted therapies in men with prostate cancer. MATERIALS AND METHODS A systematic review was carried out by searching MEDLINE, EMBASE and the Cochrane Library from inception to January 2016. Systematic reviews and randomised-controlled trials were considered for inclusion if they involved therapies directed at improving bone health or outcomes such as skeletal-related events, pain and quality of life in patients with prostate cancer either with or without metastases to bone. Therapies included medications, supplements or lifestyle modifications alone or in combination and were compared with placebo, no treatment or other agents. Disease-targeted agents such as androgen receptor-targeted and chemotherapeutic agents were excluded. Recommendations were reviewed by internal and external review groups. RESULTS In men with prostate cancer receiving androgen deprivation therapy, baseline bone mineral density testing is encouraged. Denosumab should be considered for reducing the risk of fracture in men on androgen deprivation therapy with an increased fracture risk. Bisphosphonates were effective in improving bone mineral density, but the effect on fracture was inconclusive. No medication is recommended to prevent the development of first bone metastasis. Denosumab and zoledronic acid are recommended for preventing or delaying skeletal-related events in men with metastatic castration-resistant prostate cancer. Radium-223 is recommended for reducing symptomatic skeletal events and prolonging survival in men with symptomatic metastatic castration-resistant prostate cancer. CONCLUSIONS The recommendations represent a current standard of care that is feasible to implement, with outcomes valued by clinicians and patients.

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.