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      Incidence and predictors of Bone Metastases (BM) and Skeletal-Related Events (SREs) in Small Cell Lung Cancer (SCLC): A Swiss patient cohort

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          Abstract

          Objectives: Bone metastases (BM) and skeletal-related events (SREs) are frequent complications in patients with lung cancer. Whereas in non-small-cell lung cancer (NSCLC) incidence, prognostic impact, and risk factors are well established, there is only little knowledge in patients with small cell lung cancer (SCLC). We retrospectively evaluated the incidence of BM, SRE and their treatment in a SCLC patient cohort treated at our hospital. We further assessed the role of Lactate Dehydrogenase (LDH), a possible predictor of BM development in SCLC patients.

          Materials and Methods: We retrospectively analyzed patients with the diagnosis of SCLC for BM, SRE, overall treatment patterns, outcome and established prognostic parameters by record review. The prognostic role of LDH was tested using univariate longitudinal regression analysis.

          Results: We identified 92 consecutive patients with SCLC diagnosed between 2000 and 2010 at our institution. Overall, 36.9% presented with BM at first diagnosis. Median time to BM from first diagnosis was 14.8 months (range) in limited disease (LD) and 0.9 months (range) in extensive disease (ED). The overall incidence of SRE was 18.4%. Only 19.6% of patients with BM were initially treated with bisphosphonates.

          Conclusions: Elevated LDH, as well as age ≥75 years were independent predictors for BM development in SCLC patients. Although SREs are relevant complications in SCLC, early antiresorptive treatment of BM to reduce the risk of SREs was rare. LDH served as a predictive factor for BM development in our SCLC cohort and therefore should be taken into account in future randomized controlled trials.

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          Most cited references19

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          Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study.

          Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma. Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC. Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA. In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.
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            Skeletal metastases in non-small cell lung cancer: a retrospective study.

            The skeleton is one of the most common sites of metastasis in patients with advanced cancer. Bone metastases often cause SREs (skeletal-related events). Despite advances in the treatment of primary lung cancer, SREs still affect many patients. Therefore, we planned a retrospective study to investigate the clinical impact of SREs, and to compare differences in the therapeutic outcome between patients with and without skeletal metastases or SRE. We retrospectively investigated the charts of all 259 patients with non-small cell lung cancer (NSCLC) who consulted the Department of Medical Oncology at Kinki University School of Medicine between February 2002 and January 2005. We assessed their TNM stage, presence of skeletal metastases (on bone scintigraphy, MRI, and plain X-ray films), and outcome parameters such as SREs, analgesic use, and survival. A total of 70 patients (30.4%) were found to have skeletal metastases during their clinical course and 35 patients (50%) out of all 70 patients had SREs. Among 135 stage IV patients, a total of 56 (41%) had skeletal metastases, and 25 of these 56 patients (45%) had SREs. The most common SREs were the need for radiotherapy (34.3%) and hypercalcemia (20%). Patients with SREs tended to have worse survival, while no significant difference of survival was observed between patients with and without skeletal metastases. It seems to be important to prevent SREs during the treatment of NSCLC, so further studies evaluating bisphosphonates in combination with chemotherapy are warranted.
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              Bone metastasis, skeletal-related events, and mortality in lung cancer patients: a Danish population-based cohort study.

              To estimate the incidence rate of bone metastasis and subsequent skeletal-related events (SREs) (radiation to bone, spinal cord compression, fracture, and surgery to bone) in lung cancer patients and to quantify their impact on mortality.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2016
                23 October 2016
                : 7
                : 14
                : 2110-2116
                Affiliations
                [1 ]Department of Internal Medicine, Medical Oncology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
                [2 ]Lung Tumor Center, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
                Author notes
                ✉ Corresponding author: Katrin Conen, MD, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland, katrin.conen@ 123456gmx.ch

                Conflicts of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Only the authors had access to the data used. Analysis, presentation and interpretation of the results are solely the responsibility of the authors.

                Article
                jcav07p2110
                10.7150/jca.16211
                5118675
                27877227
                e73baaba-9fb0-4eaa-8d74-dd4e7fad3c08
                © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                : 18 May 2016
                : 14 August 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                bone metastases,skeletal-related event,small cell lung cancer,ldh,predictive factor

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