Risk Factors For Bone Metastasis In Patients With Primary Lung Cancer: Systematic Review

Background:The skeleton is a common site for bone metastasis for lung cancer patients. Roughly 30%-40% of these patients develop bone metastases during the course of lung cancer. Skeletal metastases may grow to cause weakness and skeletal complications, referred to as skeletal- related events, such as pathological fractures, spinal cord compression, hypercalcemia and severe skeletal pain requiring palliative radiotherapy. Bone metastasis carries a risk of paralysis of body structures below the level of co mpression, compromising limb movement and bladder, bowel and sexual functioning. Each of these complications may result in rising cost of healthcare and reducing the quality of life. Skeletal metastases account for 350000 deaths of cancer patients each yea r. It poses a great threat to human health.Early treatment might prevent and reduce serious outcomes. Diagnostic methods include plain radiography, myelography, magnetic resonance imaging(MRI), computerised tomography(CT), radionuclide bone scanning, single-photon emission CTand positron emission tomography(PET). There have been some studies of risk factors of bone metastasis in breast and prostate cancers. But for lung cancers, it is still hard to identify and recognize who are at early stage of bone metastasis. According to previous studies, we found histology of tumour may change the risk of bone metastasis. For clinical application, the purpose of this systematic review was to identify studies investigating the risk factors of bone metastasis for pa tients who suffer from primary lung cancer, to evaluate the risk of bias or the included studies, to provide recommendations for managing to prevent lung cancer patients from having bone metastases(or skeletal-related events)Objective:To identify studies investigating the risk factors of bone metastasis, to use predefined protocol to run searches and provide a synthesis of potential risk factors for bone metastasis or skeletal-related events among lung cancers. To recognize related risk factors and identify who are the high-risk patients from considerable amount of patients.Methods:The systematic review protocol is registered with the PROSPERO International Prospective Register of Systematic Review(http://www.crd.york.ac.uk/prospero)(registration number: CRD42013003744) and reported by using the Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA) guidelines. We applied Pub Med, MEDLINE, Web of Science, EMBASE, the Cochrane Library(Cochrane Database of Systematic Reviews) and the Cochrane Central Register of Controlled Trials(CENTRAL)(until June 2014) to search the relevant literature. We followed inclusion/exclusion criteria to select studies and collect data for systematic review.We also searched for articles from references of included articles(from January 1990 to June 2014). We ran a second search at the beginning of writing this review for systematic search. Primary and secondary outcomes were bone metastase s and skeletal-related events. The heterogeneity of study outcomes and designs not fit for a meta-analysis. Therefore, this study is to provide a synthesis of potential risk factors for bone metastases or skeletal- related events among patients of lung cancer and to evaluate the overall level of evidence.Results:By systematic searches, we obtained 1615 publications without duplicates. The remaining references were retrieved as full-text for detailed assessment. O f them, 7 fulfilled the established inclusio n criteria. At the beginning of writing this report, we ran a second search for new articles, and then we included a new article. From 8 studies(6 foreign studies), we included 5 risk factors for bone metastases, and 9 risk factors for skeletal-related events.Conclusion:We found that T4 staging, N3 staging, and BSP positive expression were associated with development of bone metastasis in lung cancer patients. Furthermore, our data showed that ever-smoking and multiple bone metastases were significantly associated with higher risk of skeletal-related events in lung cancer patients with bone metastases.