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Published in: Tumor Biology 1/2016

01-01-2016 | Original Article

Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases

Authors: Arife Ulas, Ahmet Bilici, Ayse Durnali, Saadet Tokluoglu, Sema Akinci, Kamile Silay, Berna Oksuzoglu, Necati Alkis

Published in: Tumor Biology | Issue 1/2016

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Abstract

Skeletal-related events (SREs) for nonsmall cell lung cancer (NSCLC) patients with bone metastasis lead to serious morbidity. The aim of this study was to determine risk factors for SREs in NSCLC patients with bone metastasis and the factors influencing SRE-free survival and overall survival (OS). From 2000 to 2012, we evaluated retrospectively 835 NSCLC patients. Three hundred and thirty-five of them with bone metastasis were included in the study. SREs and the other prognostic factors were evaluated by univariate and multivariate analysis for SRE-free survival and OS. SREs were detected in 244 patients (72.8 %). The most common SREs were the need for radiotherapy (43.2 %) and malignant hypercalcemia (17.6 %). The median time to first SRE was 3.5 months at the median follow-up of 17 months. A multivariate analysis showed that the presence of bone metastasis at diagnosis (p < 0.001), the number of bone metastasis (p = 0.001), baseline hypercalcemia (p = 0.004), and the presence of palliative radiotherapy (p = 0.04) were independent prognostic factors for SRE-free survival. A logistic regression analysis identified that the presence of bone metastasis at diagnosis [odds ratio (OR), 12.6], number of bone metastasis (OR, 3.05), and baseline hypercalcemia (OR, 0.33) were found to be predictive factors in the developing of SRE. The median OS time for patients with SRE was worse than that for patients without SRE (7 vs 12 months, respectively). For OS, male gender, ECOG performance status (PS), high lactate dehydrogenase (LDH) level, hypoalbuminemia, the presence of bone metastasis at diagnosis, the number of bone metastasis, the presence of SREs, the presence of bisphosphonate therapy, and palliative radiotherapy were independent prognostic indicators for OS by the multivariate analysis. Our results indicated that the frequency of SREs was high and the presence of bone metastasis at the time of diagnosis, baseline hypercalcemia, and multiple bone metastases were significant factors predicting the occurrence of SREs. If bone metastases diagnose earlier, treatments for the prevention of SREs may be initiated earlier; thus, the deterioration of quality of life may be preserved.
Literature
1.
go back to reference Brenner H, Francisci S, de Angelis R, et al. Long-term survival expectations of cancer patients in Europe in 2000–2002. Eur J Cancer. 2009;45:1028–41.CrossRefPubMed Brenner H, Francisci S, de Angelis R, et al. Long-term survival expectations of cancer patients in Europe in 2000–2002. Eur J Cancer. 2009;45:1028–41.CrossRefPubMed
2.
go back to reference Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The Evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:5311–20.CrossRefPubMed Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The Evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:5311–20.CrossRefPubMed
3.
go back to reference Price N. Bisphosphonates to prevent skeletal morbidity in patients with lung cancer with bone metastases. Clin Lung Cancer. 2004;5:267–9.CrossRefPubMed Price N. Bisphosphonates to prevent skeletal morbidity in patients with lung cancer with bone metastases. Clin Lung Cancer. 2004;5:267–9.CrossRefPubMed
4.
go back to reference Qu X, Huang X, Yan W, Wu L, Dai K. A meta-analysis of FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. Eur J Radiol. 2012;81:1007–15.CrossRefPubMed Qu X, Huang X, Yan W, Wu L, Dai K. A meta-analysis of FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. Eur J Radiol. 2012;81:1007–15.CrossRefPubMed
7.
go back to reference Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21:3150–7.CrossRefPubMed Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21:3150–7.CrossRefPubMed
8.
go back to reference Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer. 2004;100:2613–21.CrossRefPubMed Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer. 2004;100:2613–21.CrossRefPubMed
9.
go back to reference Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366:1527–37.CrossRefPubMed Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366:1527–37.CrossRefPubMed
10.
go back to reference Ou SH. Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond. Drug Des Devel Ther. 2011;5:471–85.CrossRefPubMedPubMedCentral Ou SH. Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond. Drug Des Devel Ther. 2011;5:471–85.CrossRefPubMedPubMedCentral
11.
go back to reference Delea TE, McKiernan J, Brandman J, et al. Impact of skeletal complications on total medical care costs among patients with bone metastases of lung cancer. J Thorac Oncol. 2006;1:571–6.CrossRefPubMed Delea TE, McKiernan J, Brandman J, et al. Impact of skeletal complications on total medical care costs among patients with bone metastases of lung cancer. J Thorac Oncol. 2006;1:571–6.CrossRefPubMed
12.
go back to reference Hirsh V, Tchekmedyian NS, Rosen LS, et al. Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: analysis based on history of skeletal complications. Clin Lung Cancer. 2004;6:170–4.CrossRefPubMed Hirsh V, Tchekmedyian NS, Rosen LS, et al. Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: analysis based on history of skeletal complications. Clin Lung Cancer. 2004;6:170–4.CrossRefPubMed
13.
go back to reference Bae HM, Lee SH, Kim TM, Kim DW, Yang SC, Wu HG, et al. Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. Lung Cancer. 2012;77:572–7.CrossRefPubMed Bae HM, Lee SH, Kim TM, Kim DW, Yang SC, Wu HG, et al. Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. Lung Cancer. 2012;77:572–7.CrossRefPubMed
14.
go back to reference Hirsh V, Major PP, Lipton A, et al. Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity. J Thorac Oncol. 2008;3:228–36.CrossRefPubMed Hirsh V, Major PP, Lipton A, et al. Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity. J Thorac Oncol. 2008;3:228–36.CrossRefPubMed
15.
go back to reference Kohno N, Aogi K, Minami H, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2005;23:3314–21.CrossRefPubMed Kohno N, Aogi K, Minami H, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2005;23:3314–21.CrossRefPubMed
16.
go back to reference Rusch VW, Asamura H, Watanabe H, Members of IASLC Staging Committee, et al. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4:568–77.CrossRefPubMed Rusch VW, Asamura H, Watanabe H, Members of IASLC Staging Committee, et al. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4:568–77.CrossRefPubMed
17.
go back to reference Tsuya A, Kurata T, Tamura K, Fukuoka M. Skeletal metastases in non small cell lung cancer: a retrospective study. Lung Cancer. 2007;57:229–32.CrossRefPubMed Tsuya A, Kurata T, Tamura K, Fukuoka M. Skeletal metastases in non small cell lung cancer: a retrospective study. Lung Cancer. 2007;57:229–32.CrossRefPubMed
18.
go back to reference Sekine I, Nokihara H, Yamamoto N, et al. Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy. Lung Cancer. 2009;65:219–22.CrossRefPubMed Sekine I, Nokihara H, Yamamoto N, et al. Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy. Lung Cancer. 2009;65:219–22.CrossRefPubMed
19.
go back to reference Sun JM, Ahn JS, Lee S, et al. Predictors of skeletal-related events in non-small cell lung cancer patients with bone metastases. Lung Cancer. 2011;71:89–93.CrossRefPubMed Sun JM, Ahn JS, Lee S, et al. Predictors of skeletal-related events in non-small cell lung cancer patients with bone metastases. Lung Cancer. 2011;71:89–93.CrossRefPubMed
20.
go back to reference Sathiakumar N, Delzell E, Morrisey MA, et al. Mortality following bone metastasis and skeletal-related events among patients 65 years and above with lung cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999–2006. Lung India. 2013;30:20–6.CrossRefPubMedPubMedCentral Sathiakumar N, Delzell E, Morrisey MA, et al. Mortality following bone metastasis and skeletal-related events among patients 65 years and above with lung cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999–2006. Lung India. 2013;30:20–6.CrossRefPubMedPubMedCentral
21.
go back to reference Cetin K, Christiansen CF, Jacobsen JB, et al. Bone metastasis, skeletal-related events, and mortality in lung cancer patients: a Danish population-based cohort study. Lung Cancer. 2014;86:247–54.CrossRefPubMed Cetin K, Christiansen CF, Jacobsen JB, et al. Bone metastasis, skeletal-related events, and mortality in lung cancer patients: a Danish population-based cohort study. Lung Cancer. 2014;86:247–54.CrossRefPubMed
22.
go back to reference Janjan N, Lutz ST, Bedwinek JM, et al. Therapeutic guidelines for the treatment of bone metastasis: a report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology. J Palliat Med. 2009;12:417–26.CrossRefPubMed Janjan N, Lutz ST, Bedwinek JM, et al. Therapeutic guidelines for the treatment of bone metastasis: a report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology. J Palliat Med. 2009;12:417–26.CrossRefPubMed
23.
go back to reference Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage nonsmall- cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol. 1991;9:1618–26.CrossRefPubMed Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage nonsmall- cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol. 1991;9:1618–26.CrossRefPubMed
24.
go back to reference Paesmans M, Sculier JP, Libert P, et al. Prognostic factors for survival in advanced nonsmall- cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party. J Clin Oncol. 1995;13:1221–30.CrossRefPubMed Paesmans M, Sculier JP, Libert P, et al. Prognostic factors for survival in advanced nonsmall- cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party. J Clin Oncol. 1995;13:1221–30.CrossRefPubMed
25.
go back to reference Ferrigno D, Buccheri G. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients. Monaldi Arch Chest Dis. 2003;59:193–8.PubMed Ferrigno D, Buccheri G. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients. Monaldi Arch Chest Dis. 2003;59:193–8.PubMed
26.
go back to reference Katakami N, Kunikane H, Takeda K, et al. Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13. J Thorac Oncol. 2014;9(2):231–8.CrossRefPubMedPubMedCentral Katakami N, Kunikane H, Takeda K, et al. Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13. J Thorac Oncol. 2014;9(2):231–8.CrossRefPubMedPubMedCentral
27.
go back to reference Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89:877–85.CrossRefPubMedPubMedCentral Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89:877–85.CrossRefPubMedPubMedCentral
28.
go back to reference Danner BC, Didilis VN, Wiemeyer S. Long-term survival is linked to serum LDH and partly to tumour LDH-5 in NSCLC. Anticancer Res. 2010;30:1347–51.PubMed Danner BC, Didilis VN, Wiemeyer S. Long-term survival is linked to serum LDH and partly to tumour LDH-5 in NSCLC. Anticancer Res. 2010;30:1347–51.PubMed
29.
go back to reference Jafri SH, Shi R, Mills G. Advance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective review. BMC Cancer. 2013;13:158–67.CrossRefPubMedPubMedCentral Jafri SH, Shi R, Mills G. Advance lung cancer inflammation index (ALI) at diagnosis is a prognostic marker in patients with metastatic non-small cell lung cancer (NSCLC): a retrospective review. BMC Cancer. 2013;13:158–67.CrossRefPubMedPubMedCentral
30.
go back to reference Forrest LM, McMillan DC, McArdle CS. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89:1028–30.CrossRefPubMedPubMedCentral Forrest LM, McMillan DC, McArdle CS. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89:1028–30.CrossRefPubMedPubMedCentral
32.
go back to reference Trinkaus M, Simmons C, Myers J. Skeletal-related events (SREs) in breast cancer patients with bone metastases treated in the nontrial setting. Support Care Cancer. 2010;18:197–203.CrossRefPubMed Trinkaus M, Simmons C, Myers J. Skeletal-related events (SREs) in breast cancer patients with bone metastases treated in the nontrial setting. Support Care Cancer. 2010;18:197–203.CrossRefPubMed
33.
go back to reference De Marinis F, Eberhardt W, Harper PG. Bisphosphonate use in patients with lung cancer and bone metastases: recommendations of a European expert panel. J Thorac Oncol. 2009;4:1280–8.CrossRefPubMed De Marinis F, Eberhardt W, Harper PG. Bisphosphonate use in patients with lung cancer and bone metastases: recommendations of a European expert panel. J Thorac Oncol. 2009;4:1280–8.CrossRefPubMed
34.
go back to reference Song Z, Zhang Y. Zoledronic acid treatment in advanced non-small cell lung cancer patients with bone metastases. Med Oncol. 2014;31:898–906.CrossRefPubMed Song Z, Zhang Y. Zoledronic acid treatment in advanced non-small cell lung cancer patients with bone metastases. Med Oncol. 2014;31:898–906.CrossRefPubMed
35.
go back to reference Hu X, Zou Q, Jin C. Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30:1343–6 (Abstract).PubMed Hu X, Zou Q, Jin C. Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30:1343–6 (Abstract).PubMed
Metadata
Title
Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases
Authors
Arife Ulas
Ahmet Bilici
Ayse Durnali
Saadet Tokluoglu
Sema Akinci
Kamile Silay
Berna Oksuzoglu
Necati Alkis
Publication date
01-01-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3907-z

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