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      Natural History of Malignant Bone Disease in Gastric Cancer: Final Results of a Multicenter Bone Metastasis Survey

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          Abstract

          Background

          Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available.

          Patients and Methods

          Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed.

          Results

          Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005).

          Conclusions

          To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients.

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          Most cited references15

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          Gastric cancer epidemiology and risk factors.

          Gastric cancer is a prevalent yet heterogeneous disease. From diet and lifestyle to genetics and ethnicity, our appreciation of the complexity of gastric cancer has evolved. This review will discuss the epidemiology of gastric cancer focusing on trends across various risk categories. We realize that gastric cancer is not merely a single disease, but rather individual diseases within a single organ-a distinction that will aid our understanding of disease heterogeneity and its significance. Copyright © 2012 Wiley Periodicals, Inc.
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            Metastases in carcinoma; analysis of 1000 autopsied cases.

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              Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group.

              Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                28 October 2013
                : 8
                : 10
                : e74402
                Affiliations
                [1 ]Medical Oncology Unit, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari, Italy
                [2 ]Medical Oncology Unit, University Campus Bio-Medico, Roma, Italy
                [3 ]Osteoncology and Rare Tumors Center, IRCCS -Romagnolo Scientific Institute for the Study and Treatment of Cancer, Meldola, Italy
                [4 ]Medical Oncology Unit, Hospital of Frosinone, Frosinone, Italy
                [5 ]Medical Oncology Unit, II University of Naples, Naples, Italy
                [6 ]Medical Oncology Unit, Hospital of Latina, Latina, Italy
                [7 ]Department of Oncology-Hematology, Hospital of Pavia, Pavia, Italy
                [8 ]Division of Medical Oncology, Treviglio-Caravaggio Hospital, Treviglio, Italy
                [9 ]Operative Unit of Oncology - IRCCS Fondazione Maugeri, Pavia, Italy
                [10 ]Medical Oncology Unit, Hospital of Benevento, Benevento, Italy
                [11 ]Department of Medical Oncology, San Giovanni Battista Hospital, Turin, Italy
                [12 ]Department of Medical Oncology, Fondazione Poliambulanza of Brescia, Brescia, Italy
                [13 ]Medical Oncology Unit, Hospital of Pesaro, Pesaro, Italy
                [14 ]Medical Oncology Unit, Hospital Careggi, Florence, Italy
                [15 ]Department of Oncology, Gradenigo Hospital and Gruppo Piemontese Sarcomi, Turin, Italy
                [16 ]Medical Oncology Unit, Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
                [17 ]Medical Oncology Unit, Hospital “Cardarelli”, Naples, Italy
                [18 ]Medical Oncology Unit, Hospital of Barletta, Barletta, Italy
                [19 ]Medical Oncology Unit, Hospital of Aosta, Aosta, Italy
                [20 ]Medical Oncology Unit, University of Ancona, Ancona, Italy
                [21 ]Medical Oncology Unit, Hospital of Lecce, Lecce, Italy
                [22 ]Medical Oncology Unit, Hospital of Sondrio, Sondrio, Italy
                [23 ]Medical Oncology Unit, Hospital Regina Apostolorum, Albano Laziale, Italy
                [24 ]Medical Oncology Department & Breast Unit – Hospital of Brindisi and Medical Oncology Department – European Institute of Oncology, Milan, Italy
                [25 ]Medical Oncology Unit, University of Palermo, Palermo, Italy
                [26 ]Medical Oncology Departement Hospital of Taranto, Taranto, Italy
                [27 ]Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Bari, Italy
                Shanghai Jiao Tong University School of Medicine, China
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: NS DS. Performed the experiments: FP. Analyzed the data: FP DS NS. Contributed reagents/materials/analysis tools: TI TG FDV TDP PP SB AF MAS PB VC EG AC EM FR RF AT RB SL AB FA SC AR SP AEB. Wrote the paper: NS DS. Helped to draft and revise the manuscript: AA.

                Article
                PONE-D-13-06610
                10.1371/journal.pone.0074402
                3810275
                24204569
                c7f276f4-7dd8-4f42-b80e-6742bf8b7427
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 February 2013
                : 1 August 2013
                Page count
                Pages: 8
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article

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