Data on cumulative scores for

Data on cumulative scores for both BPI and FACT-BP have been reported elsewhere [7]. Here, we also assessed item-level scores such as average pain over the past 7 days, worst pain over the past 7 days, and pain right now.
Results A total of 38 patients were randomized with 19 patients in each arm, and 29 patients completed FACT-BP and BPI at baseline. At week 12, data was available for correlation of pain scores with bone turnover marker levels for 22 patients, 11 patients completed questionnaires at week 48 (Table 2).
Conclusion Despite skeletal morbidity being associated with reduced quality of life and shortened survival, a reduction in the rate of skeletal related events (SREs) with bone-targeted agents has not shown any improvement in global quality of life scores or survival [8–12]. This raises a question regarding the sole use of SREs as clinically relevant endpoints. Bone pain is usually the earliest and most common symptom in patients developing skeletal metastases. Patient-reported bone pain reflects an individual patient\'s experience regarding pain severity and its impact on functioning and QoL. Bone pain is a logical candidate for evaluating treatment efficacy. Several groups have therefore been developing scores that are meaningful, valid, easy and fast to complete and assess. Matza and colleagues measured bone pain in oncology trials, and concluded that most approaches used simple assessment of general bodily pain, often with single items [2]. They recommended that bone pain assessment tools be validated within the target e1 activating enzyme (i.e., people with bone pain), and have sufficient content validity to represent the important concerns and specific impact of this unique pain experience. The Functional Assessment of Cancer Therapy-Bone Pain (FACT-BP) was developed in 2004 and published in 2009 [5], to provide such a tool. Similarly, others have tried to link biomarkers of bone turnover with a range of other pertinent surrogates [13]. The current results show that FACT-BP and BPI correlated well with each other over time. In addition, using either of these methods of assessment of pain, no differences were observed between the pain scores in the two study arms. While interestingly, we acknowledge the limitations of the current study. REFORM was a small randomized pilot study, thus it remains possible that the small number of patients analyzed presently could impact the present results. However, our findings support the use of FACT-BP in larger cohorts assessing bone targeted trials, particularly those focused on patients considered to be at low risk, as levels of the standard bone turnover biomarkers CTx and BSAP may not truly reflect the impact of the disease on a patient\'s well being. Our reasoning for this choice is that it correlates quite well with the most commonly-used pain instrument in prior bone pain trials, the BPI, and yet it introduces a wider variety of content which enhances the validity and applicability of the assessment to patients\' lives [2]. We thus plan to incorporate FACT-BP in larger bone-targeted trials for further evaluation of its validity.
Conflict of interest statement
Acknowledgments Funded by the Division of Medical Oncology at Princess Margaret Hospital, Toronto, Canada. No pharmaceutical company funding was received. The authors acknowledge the roles of Esther Lee and Tazmin Usmani in trial coordination and Dr. Ranjeeta Mallick for statistical analysis.
Introduction The skeleton is a common site of metastatic disease, affecting a large number of patients with advanced cancer [1]. Around 70% of patients who die of prostate and breast cancer concurrently experience bone metastasis and the incidence in kidney, thyroid and bronchus carcinomas reported to be around 30–40%. In contrast, tumours of the gastrointestinal tract rarely metastasise to the skeleton (∼5%) [2]. Metastasis to bone usually signifies an increased morbidity due to skeletal-related events, including bone pain, nerve and spinal cord compression syndrome, hypercalcaemia and pathologic fractures. As a result, the quality of life of the affected individuals may be greatly diminished [1]. Despite significant improvements in the outcome of patients with organ-confined cancer, patients with metastatic disease have not shared the same advances [3]. In an effort to maintain quality of life, improve survival as well as increase therapeutic options available for patients with bone metastasis, the underlying mechanisms should be investigated and understood. A number of complex steps are involved in the formation of bone metastasis, involving a myriad of interactions between different cell types in conjunction with a large number of soluble factors, extracellular matrix components, hormones, physical properties [3]. Increasing evidence suggest that macrophages contribute both to primary tumour growth and to the subsequent development of metastasis [4]. However, there is very limited evidence for a specific role of macrophages in development and progression of bone metastasis. In this review we will give a brief overview of the current understanding of the contribution of macrophages to cancer metastasis, with particular emphasis on the involvement in tumour spread to the skeleton.