br Methods The prevalence of various fractionation schedules
Methods The prevalence of various fractionation schedules was extracted from each of the final articles included in the review. Other relevant information, such as significant predictive factors for the use of single fraction herpes simplex virus type 1 therapy, changes in the prevalence of fractionation schedules over time, and types of bone metastases irradiated, was also included. The flow chart describing the inclusion process for the articles can be found in Fig. 1.
Discussion The majority of advanced cancer patients will develop bone metastases at some point in their illness [1,2]. As such, optimal management of bone metastases is central to patient care. Optimal management involves considering all risks and costs of treatment with appropriate goals of care in mind. In advanced cancer patients, these goals of care are palliative in intent and should be centered on improving pain and QOL . A recent systematic review on randomized control trials investigating the efficacy of various dose fractionation schedules was published by Chow et al. in 2012 . The authors identified 25 RCTs and concluded that both SFRT and MFRT were equally efficacious in providing pain relief. Retreatment rates were greater in patients treated with a single fraction; however, this may be a product of the increased likelihood for physicians to offer re-irradiation to patients who have been treated with lower overall doses . Other meta-analyses [41,42] have been previously published, concluding similar results to Chow et al. Different trials have been conducted to evaluate dose fractionation schedules in complicated bone metastases, such as those presenting with neuropathic pain, at risk of fracture, and spinal cord compression. In these circumstances, multiple fractions may have increased efficacy, especially in those with greater prognosis [8,9,43]. As expected, treatments of a single fraction are more cost effective compared to multiple treatments. Konski et al.  conducted an economic analysis on the Radiation Therapy and Oncology Group (RTOG) 97-14 trial, which investigated the efficacy of single versus multiple fractions in pain relief caused by bone metastases from breast and prostate cancer. The authors concluded that, even with the potential for greater re-treatments with SFRT, a single treatment is still more cost effective when compared to multiple. This study did not factor in patient cost of travel and lost productivity, which would further confirm SFRT as cost effective as less patient visits are required . Findings were similar in a study by van den Hout et al. , who found that the cost of SFRT and MFRT was $2438 and $3311, respectively. These figures include potential re-treatments in both groups. When the authors included societal costs, the estimated expenses increased to $4700 for SFRT and $6453 for MFRT . Again, this study clearly favours single fraction treatments as more cost effective when compared to protracted radiotherapy courses. In light of the various published randomized control trials and meta-analyses, guidelines regarding appropriate dose fractionation schedules have been released by several cancer organizations. Cancer Care Ontario (CCO) is a predominant cancer organization in Ontario, Canada, and went through an extensive process with radiation oncologists across the province to develop a guideline for appropriate dose fractionation schedules. The ultimate recommendation of this 2004 guideline was the use of a single 8Gy RT course to palliate symptomatic uncomplicated bone metastases . The American College of Radiology (ACR) most recently in 2009, on recommendation of an expert panel, stated that a single fraction was just as efficacious as multiple fractions in the relief of uncomplicated bone pain. Furthermore, they concluded that SFRT is likely more desirable in patients with poor prognosis and that SFRT is more cost effective when compared to MFRT . A similar evidence based guideline was released in 2011 by ASTRO and reinforced the recommendation that a single 8Gy be used to palliate uncomplicated bone metastases . Overall, although there has been some increase in the prescription of SFRT seen in this review, the guidelines and meta-analyses have not had a significant impact on international patterns of practice to date.