Carmel Jacobs

Clinical Practice Guidelines and Consensus Statements in Oncology – An Assessment of Their Methodological Quality

Background Consensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine’s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicines standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents. Findings Thirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal’s consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases. Conclusion Guidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor’s product to enhance transparency.

Are adjuvant bisphosphonates now standard of care of women with early stage breast cancer? A debate from the Canadian Bone and the Oncologist New Updates meeting.

The 9th Bone and the Oncologist New Updates conference was held in Ottawa, Canada during 2014. This annual meeting focuses on innovative research into the mechanisms and consequences of treatment-induced and metastatic bone disease. Given the recent presentation of the Oxford overviews “Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomized trials” at the San Antonio Breast Cancer Symposium, a debate as to the pros and cons of adjuvant bisphosphonate use in early stage breast cancer was undertaken. As bisphosphonate treatment in post-menopausal women appeared to demonstrate a similar magnitude of benefit to that of other commonly used adjuvant strategies the debate assessed whether or not there was sufficient data to incorporate adjuvant bisphosphonates into standard practice and if so, in which patient populations.

Pharmacotherapy of bone metastases in breast cancer patients – an update

Introduction: Bone metastases in breast cancer patients are a common clinical problem and pose a threat to the quality of life of such patients. Multiple randomized trials have demonstrated the benefit of both bisphosphonates and denosumab in reducing the incidence and delaying the onset of skeletal related events (SREs) in breast cancer patients with bone metastases. Areas covered: We review the current literature on the use of bisphosphonates and denosumab along with strategies to maximize benefit and minimize risk of these agents. We also review potential future targets. Expert opinion: Despite the potent osteoclast inhibiting effects of the bone-targeted agents in current clinical use, we have likely maximized their ability to inhibit SREs and must in turn focus on minimizing their potential toxicity. The future will likely involve more novel treatment strategies as well as the development of new agents. The current ‘one size fits all’ approach for the management of breast cancer bone metastases will be replaced by ‘tailored’ treatment for each individual patient as we usher in the era of ‘personalized medicine.’ In addition, new bone-targeted agents (e.g., sclerostin inhibitors) and combinations will continue to be explored, as will the evaluation of the bone-targeting properties of more conventional non-osteoclast targeting therapies.

Definition and consequences of locally advanced breast cancer.

Purpose of reviewLocally advanced breast cancer (LABC) represents the most advanced stage breast cancer that is still potentially curable with surgery, radiation, and systemic therapy. The purpose of this review is to discuss LABC in the context of modern practice with a focus on its definition and potential consequences. Recent findingsThere is no one encompassing definition for this disease, but in general cancers of the breast are considered to be locally advanced if they are large and/or have infiltrated into adjacent tissues (the overlying skin or underlying muscles) and/or are found to have extensive locoregional lymph node involvement. It is not surprising, therefore, that LABC can cause significant morbidity and mortality. SummaryRecent advances in our understanding of the biology of breast cancer have made it clear that LABC does not represent a single clinical entity but rather a heterogeneous group of breast tumors that share a common theme of extensive locoregional spread without overt evidence of distant metastatic disease. Despite advances in breast cancer screening and treatment LABC remains a significant global healthcare issue.

Bone-targeted therapy use in patients with bone metastases from lung cancer: A systematic review of randomized controlled trials

BACKGROUND Patients with advanced lung cancer commonly have bone metastases. Compared with other malignancies, the use of bone-targeted agents (e.g. bisphosphonates and denosumab) is less common in lung cancer patients. This may be due to the perception that bone-targeted agents are less effective in this population. OBJECTIVE To perform a systematic review to evaluate data from randomized trials of bone-targeted agents in lung cancer patients with bone metastases. METHODS A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials through May 2015 was performed. Randomized trials of bone-targeted therapies in lung cancer patients with bone metastases were sought. Outcomes studied included skeletal related events (SREs), pain, quality of life, progression-free survival and overall survival. Random effects meta-analyses were planned if studies were judged homogeneous. RESULTS Of 632 abstracts, 17 publications describing 13 studies were included. Sample sizes ranged between 50 and 1776. Of 3379 patients, 1903 had lung cancer, with subgroup data available for 8 of 13 studies. Patient demographics were comparable, but enrollment criteria and endpoints were heterogeneous across studies, precluding meta-analysis. Study-specific results suggested that bone-modifying agents reduce the incidence of SREs and bone pain in lung cancer patients. Three studies suggested a survival benefit. CONCLUSION Data from included trials suggests benefit of bone-targeted agents in lung cancer for the prevention of SREs and bone pain. There is a trend toward improvement in overall survival and progression-free survival, although further research is needed. Impact on quality of life and key subgroups for benefit both require future research.

Lost in Transition? Thoughts on Retirement—“Will You Still Need Me, Will You Still Feed Me, When I'm Sixty-Four?”

Oncologists should plan for a future beyond full-time oncology, but there is little practical guidance for a successful transition into retirement. This paper provides strategies for various aspects of retirement planning and transitioning. More prospective information is needed.

Long-term benefits versus side-effects from bone-targeted therapies for cancer patients: minimizing risk while maximizing benefits.

Purpose of reviewBone-targeted therapies such as bisphosphonates and denosumab are established in the treatment of cancer patients to prevent or delay skeletal-related events and improve quality of life. Along with these benefits of bone-targeted therapies, there are also known risks and adverse effects. Recent findingsAlthough historically bone-targeted therapy use has been limited to palliation in patients with bone metastases, recent evidence suggests that these agents may also have anti-cancer effects. This will likely lead to the greater use of these agents in patients with earlier-stage disease. Increased use will lead to more adverse effects. In particular, the risk of rare but severe toxicities will become important. SummaryThis article explores strategies to maximize the clinical benefit of such therapy while minimizing associated risks.

Publishing clinical research: ten pearls for oncology trainees and junior oncologists

The old adage of “publish or perish” bears some truth. As the lines between “academic” and “community” practice blur, more physicians are expected to participate in “scholarly activities.” Such activities will be required regardless of career path in clinical care, education, research, or administration. A successful research project can set oncology hopefuls apart from other applicants and can drive conversations at interviews. Research can also provide opportunities to attend conferences, where networking with other researchers is critical to one’s work and general career development. For oncologists, peer-reviewed publications are an objective indicator of productivity, an important component of annual assessments, and an integral component of university promotion processes. Although research is not for everyone, seeing a project through to peer-reviewed publication carries great merit because of the effort and persistence it requires. Previous publications have outlined how to conduct research1,2 and the importance of having a good mentor3–6. We hope that the present article, with its 10 pragmatic tips, will help junior researchers ultimately to publish their work. Although not every point is supported by a peer-reviewed publication (or at times by specific evidence), our tips are derived from conversations with other researchers and from our own experiences with editing, publishing, and (we must admit) countless rejections. As authors, we reflect all stages of training—university graduate (SM), resident (MF), research fellow (CJ), junior faculty (AA), and old-timer (MC)—and we hope that the “pearls,” while not telling the whole story, will at least provoke lively debate.

A Systematic Review of the Incidence and Risk Factors for Taxane Acute Pain Syndrome in Patients Receiving Taxane-Based Chemotherapy for Prostate Cancer

&NA; Taxane acute pain syndrome (TAPS) is characterized by myalgia and arthralgia starting 24 to 48 hours after taxane‐based chemotherapy and lasting ≤ 7 days. Little is known about its incidence and predisposing factors in patients with prostate cancer. A systematic review was performed to identify studies reporting the incidence and risk factors for TAPS in patients receiving taxane‐based chemotherapy for prostate cancer. Embase, Ovid Medline, and other nonindexed citations were searched from 1947 to July 7, 2015. Randomized trials and prospective observational studies reporting the outcomes for prostate cancer patients who had received taxane‐based chemotherapy were assessed. Four reviewers independently screened the citations and full text reports for data collection. Of 980 citations, 5 studies (2710 patients) met the eligibility criteria. The incidence of myalgia and arthralgia was reported in 4 trials (14%, [29% and 38%], 44.2%, and 46%). TAPS was not reported with cabazitaxel chemotherapy. Clinical risk factors were identified in 4 studies, suggesting that TAPS was numerically more common in the castrate‐resistant setting and when concurrent medications (eg, corticosteroids) were not used. Although the TAPS incidence has been poorly reported in clinical practice, the results of the present study suggest that arthralgia and myalgia are a common toxicity in patients with prostate cancer. An improved and universal definition of TAPS, patient‐directed reporting of TAPS, and improved standardized assessments are needed to better identify patients at the greatest risk of experiencing TAPS and improving patient care.

Enhancing accrual to chemotherapy trials for patients with early stage triple-negative breast cancer: a survey of physicians and patients

PurposeThe optimal chemotherapy regimen for patients with early stage triple-negative breast cancer (TNBC) remains unknown. The purpose of the study is to survey physicians and breast cancer patients about preferred chemotherapy regimens for early stage TNBC and clinical trial strategies.MethodsA standardised online questionnaire was developed and circulated to medical oncologists known to treat breast cancer. A separate questionnaire was given to patients who had received chemotherapy for breast cancer.ResultsThe questionnaire was completed by 41/84 medical oncologists (48.8% response rate) and 74 patients. The most commonly used neoadjuvant and adjuvant chemotherapy regimens for TNBC were dose-dense doxorubicin and cyclophosphamide (AC)–paclitaxel (P), dose-dense AC followed by weekly P and fluorouracil, epirubicin, cyclophosphamide–docetaxel (FEC-D). The majority of medical oncologists (80%) would be willing to enrol patients in trials evaluating the most effective chemotherapy regimen for TNBC. Oncologists favoured a three arm trial design comparing currently available standard of care treatments (36%) and trials of novel or non-standard of care agents 22% (9/41). Sixty percent (41/74) of patients indicated that they would be willing to be enrolled in trials evaluating various adjuvant regimens for TNBC. Both oncologists and patients were interested in novel consent approaches such as using the integrated consent model.ConclusionOptimisation of chemotherapy for TNBC is an important and unmet clinical need. It is apparent that various chemotherapy regimens are used for patients with early stage TNBC. The majority of medical oncologists and patients are interested in entering trials to optimise chemotherapy choices.