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      Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data

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          Abstract

          Background. Serum alkaline phosphatase (SALP) is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs) and relative risks (RRs) with corresponding confidence intervals (CIs) were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients' overall survival (OS) (HR = 1.82; 95% CI: 1.61–2.06; p < 0.001) and event-free survival (EFS) (HR = 1.97; 95% CI: 1.61–2.42; p < 0.001). Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p = 0.006). No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

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          Most cited references53

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            Osteosarcoma.

            The successful treatment of patients with osteosarcoma requires close cooperation within an experienced multidisciplinary team including pediatric or medical oncologists, surgeons, pathologists and radiologists. Therefore, therapy should be performed in specialized centers able to provide access to the full spectrum of care. As in other rare malignancies, treatment should be administered within prospective multicenter trials. Therapy must include complete surgical removal of all detectable tumor sites as well as multiagent chemotherapy. The chemotherapy regimen should include several or all of the following four drugs: doxorubicin, high-dose methotrexate with leukovorin-rescue, cisplatin and ifosfamide. Preoperative (neoadjuvant) plus postoperative (adjuvant) polychemotherapy should be preferred, because it allows preparation for safe surgery and preparation of the appropriate prosthesis for the individual patient. The choice of the postponed definitive surgical procedure should be influenced by the anatomical site of the primary tumor, its relationship to neighboring structures, such as vessels and nerves, age and growth potential of the patient, and probably also by the response of the tumor to preoperative chemotherapy. A major, as yet unsolved, problem is the dismal prognosis for patients with unresectable or relapsed osteosarcomas. Novel approaches are needed in order to improve their prognosis.
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              A Meta-Analysis of Osteosarcoma Outcomes in the Modern Medical Era

              Four decades ago, specialized chemotherapy regimens turned osteosarcoma, once considered a uniformly fatal disease, into a disease in which a majority of patients survive. Though significant survival gains were made from the 1960s to the 1980s, further outcome improvements appear to have plateaued. This study aims to comprehensively review all significant, published data regarding osteosarcoma and outcome in the modern medical era in order to gauge treatment progress. Our results indicate that published survival improved dramatically from 1960s to 1980s and then leveled, or in some measures decreased. Recurrence rates decreased in the 1970s and then leveled. In contrast, published limb salvage rates have increased significantly every recent decade until the present. Though significant gains have been made in the past, no improvement in published osteosarcoma survival has been seen since 1980, highlighting the importance of a new strategy in the systemic management of this still very lethal condition.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2015
                4 November 2015
                : 2015
                : 160835
                Affiliations
                Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China
                Author notes

                Academic Editor: Dominic Fan

                Article
                10.1155/2015/160835
                4649087
                26618165
                cdc604b4-6113-4a1d-936c-8130bb1bddbb
                Copyright © 2015 Hai-Yong Ren et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 July 2015
                : 12 October 2015
                Categories
                Review Article

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