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  • br Conclusion The mm Jamshidi is feasible practical

    2019-04-26


    Conclusion The 2mm Jamshidi is feasible, practical, and yields an adequate sample to assess bone structure and quality using microCT and histomorphometry in breast cancer patients. Additional samples are required to assess reproducibility, effect of bisphosphonates on bone quality and novel information on bone/tumor interaction. Further research is required to determine whether this technique may be to longitudinally assess bone quality in cancer patients on long-term bone-targeted therapies.
    Acknowledgments We acknowledge support from Renee Amours-Ouellette and her family and “Tina and her Angels of Hope Fund” (MC). This research was also supported by grants from Canadian Institutes for Health Research(CIHR) MOP-10839 and the Susan G Komen Foundation grant KG 100766(to RK).
    Introduction Metastatic disease in advanced cancer most commonly manifests itself in bone. Of all advanced breast or prostate cancer, 65% to 75% of patients develop metastases to bone, while in patients with other solid tumours 30% to 40% of patients will develop bone metastases [1]. Patients with bone metastases are at a high risk of developing SREs (such as bone pain requiring analgesics or palliative ST 2825 therapy, spinal cord compressions (SCC), pathological fractures, hypercalcemia, or a need for surgery), which can greatly reduce quality of life (QOL) [3]. Retrospective analyses of several tumour types have demonstrated that patients with bone metastases who experience an SRE are more likely to experience subsequent SREs [2]. SREs undermine patients’ functioning, beget significant morbidity, and reduce patients’ survival. As treatment intent for patients with advanced cancers shifts from survival to the preservation of QOL, the principal objective becomes the management and prevention of SREs secondary to bone metastases. “Skeletal-related complications” as a quantifiable clinical end point were first defined as pathologic fractures, irradiation of or surgery on bone, spinal cord compression, or hypercalcemia of malignancy (HCM); they were first applied to studies assessing pamidronate in women with bone metastases from breast cancer [3]. In the past, HCM was highly prevalent in breast cancer patients with bone metastases [3]; but today, it is a condition that is rarely seen due to a better understanding of the disease and the frequent use of anti-resorptive therapies. Therefore, in more recent studies, HCM has been excluded in the standard SRE definition. This is appropriate, as comparisons of HCM rates reported in studies performed in the 1990s show significantly lower rates of HCM than those conducted in the 1970s and 1980s [4]. In a retrospective analysis of patients with breast cancer from 1975 to 1984 who had first recurrence of disease in the bone, 17% developed hypercalcemia [5]. In the placebo arm of a study evaluating the safety of cyclic pamidronate in breast cancer patients, where study enrolment began in 1990, the incidence of hypercalcemia in patients with lytic bone disease was 13%, compared with 6% in the pamidronate arm [4]. The introduction of bone targeting agents to patients’ treatment has been shown to be beneficial in preventing SREs and reducing pain in large phase III trials. Bone targeted therapies have been found to prolong the time to first SRE and reduce the rate of SREs [6]. The introduction of new anti-resorptive therapies into clinical practice, such as the nitrogen-containing IV bisphosphonate pamidronate early in the 1990s, zoledronic acid from 2000, and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab in 2010 is accompanied by increased disease state awareness. Consequently, general standards of care in the skeletal health of cancer patients have improved. Nonetheless, SREs remain a common problem for patients with bone metastases from advanced cancer. As such, curtailing SREs will have benefits for the healthcare system in terms of reduced patient morbidity and lower healthcare costs [7]. The skeletal morbidity rate (SMR) is defined as the ratio of the number of SREs for each subject divided by the subject’s time at risk in years. For example, if a study follows 1000 patients for one year and among those 1000 patients 350 SREs occur, then the SMR value would be 0.35 SREs/year. If multiple events are experienced within a year these values are included within the ratio.