Risk Factors for Skeletal-related Events in Non-small Cell Lung Cancer Patients Treated with Bone-modifying Agents

Overview

Journal Support Care Cancer

Specialties Critical Care
Oncology

Date 2021 Jan 6

PMID 33404803

Citations 3

Authors

Go Saito

Takahiro Ebata

Tsukasa Ishiwata

Shunichiro Iwasawa

Ichiro Yoshino

Yuichi Takiguchi

Koichiro Tatsumi

Affiliations

Soon will be listed here.

Abstract

Purpose: The risk factors for skeletal-related events (SREs) among non-small cell lung cancer (NSCLC) patients during treatment with bone-modifying agents (BMAs) are not yet well-understood.

Methods: The medical records of 238 consecutive NSCLC patients treated with BMAs, including zoledronic acid and denosumab, at the Chiba University Hospital from 2012 to 2016 were reviewed in the present study. SREs were defined as either pathologic fractures, spinal cord compression, the need for bone irradiation or surgery, or hypercalcemia. The risk factors for earlier occurrence of the first SRE from the time of the first bone metastasis diagnosis after the initiation of BMA treatment were identified.

Results: Of the 238 included patients, 92% (n = 220) had a performance status (PS) of 0-2 at diagnosis of bone metastasis. Forty-eight (20%) patients developed at least one SRE. The most common first SRE was the need for bone irradiation surgery (n = 27, 56%). Significant risk factors included poor PS (hazard ratio [HR]: 4.36; p = .024), male sex (HR: 2.17; p = .022), and the use of zoledronic acid (HR: 1.91; p = .032). The overall survival (OS) from the first bone metastasis diagnosis was 394 days (95% confidence interval [CI]: 331-465). The OS of patients with PS 3 and 4 at the diagnosis of bone metastasis (median: 36 days; 95% CI: 13-50) was significantly (p < 0.0001) shorter than that of patients with PS 0-2 (median: 411 days; 95% CI: 354-558) (HR: 4.53; 95% CI: 2.62-7.35).

Conclusions: Careful observation is needed for patients with the identified risk factors, which include poor PS and male sex, despite the BMA treatment.

Citing Articles

Pulmonary Rehabilitation in Patients with Operable Non-Small Cell Lung Cancer.

Zhong J, Trinh I, Raju S, Hsu M J Clin Med. 2025; 14(3).

PMID: 39941440 PMC: 11818806. DOI: 10.3390/jcm14030770.

Prognostic factors in patients with bone metastasis of lung cancer after immune checkpoint inhibitors: A retrospective study.

Ishibashi Y, Kobayashi H, Ando T, Okajima K, Oki T, Tsuda Y World J Orthop. 2025; 15(12):1155-1163.

PMID: 39744733 PMC: 11686526. DOI: 10.5312/wjo.v15.i12.1155.

Analysis of the Mechanism and Safety of Bisphosphonates in Patients with Lung Cancer and Bone Metastases.

Zhang G, Gong H, Xu H Comput Math Methods Med. 2021; 2021:5343104.

PMID: 34938354 PMC: 8687786. DOI: 10.1155/2021/5343104.

Risk evaluation of denosumab and zoledronic acid for medication-related osteonecrosis of the jaw in patients with bone metastases: a propensity score-matched analysis.

Ikesue H, Doi K, Morimoto M, Hirabatake M, Muroi N, Yamamoto S Support Care Cancer. 2021; 30(3):2341-2348.

PMID: 34738163 PMC: 8794983. DOI: 10.1007/s00520-021-06634-7.

References

Xu Z, Yang Q, Chen X, Zheng L, Zhang L, Yu Y . Clinical associations and prognostic value of site-specific metastases in non-small cell lung cancer: A population-based study. Oncol Lett. 2019; 17(6):5590-5600. PMC: 6507334. DOI: 10.3892/ol.2019.10225. View

Tamura T, Kurishima K, Nakazawa K, Kagohashi K, Ishikawa H, Satoh H . Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol. 2014; 3(1):217-221. PMC: 4251107. DOI: 10.3892/mco.2014.410. View

Kuchuk M, Kuchuk I, Sabri E, Hutton B, Clemons M, Wheatley-Price P . The incidence and clinical impact of bone metastases in non-small cell lung cancer. Lung Cancer. 2015; 89(2):197-202. DOI: 10.1016/j.lungcan.2015.04.007. View

Santini D, Daniele S, Barni S, Sandro B, Intagliata S, Salvatore I . Natural History of Non-Small-Cell Lung Cancer with Bone Metastases. Sci Rep. 2015; 5:18670. PMC: 4687045. DOI: 10.1038/srep18670. View

Weinfurt K, Li Y, Castel L, Saad F, Timbie J, Glendenning G . The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol. 2005; 16(4):579-84. DOI: 10.1093/annonc/mdi122. View

Kunikane H, Yokota I, Katakami N, Takeda K, Takayama K, Sawa T . Prospective analysis of the association between skeletal-related events and quality of life in patients with advanced lung cancer (CSP-HOR13). Oncol Lett. 2019; 17(1):1320-1326. PMC: 6312953. DOI: 10.3892/ol.2018.9680. View

Bongiovanni A, Recine F, Fausti V, Foca F, Casadei R, Falasconi M . Ten-year experience of the multidisciplinary Osteoncology Center. Support Care Cancer. 2019; 27(9):3395-3402. DOI: 10.1007/s00520-019-4635-5. View

Rosen L, Gordon D, Tchekmedyian N, Yanagihara R, Hirsh V, Krzakowski M . 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(12):2613-21. DOI: 10.1002/cncr.20308. View

Henry D, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J . Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011; 29(9):1125-32. DOI: 10.1200/JCO.2010.31.3304. View

10.

Planchard D, Popat S, Kerr K, Novello S, Smit E, Faivre-Finn C . Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv192-iv237. DOI: 10.1093/annonc/mdy275. View

11.

Nakahara Y, Hosomi Y, Shibuya M, Mitsufuji H, Katagiri M, Naoki K . Multicenter study of zoledronic acid administration in non-small-cell lung cancer patients with bone metastasis: Thoracic Oncology Research Group (TORG) 1017. Mol Clin Oncol. 2019; 11(4):349-353. PMC: 6713944. DOI: 10.3892/mco.2019.1903. View

12.

Sekine I, Nokihara H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T . Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy. Lung Cancer. 2008; 65(2):219-22. DOI: 10.1016/j.lungcan.2008.10.026. View

13.

Sun J, Ahn J, Lee S, Kim J, Lee J, Park Y . Predictors of skeletal-related events in non-small cell lung cancer patients with bone metastases. Lung Cancer. 2010; 71(1):89-93. DOI: 10.1016/j.lungcan.2010.04.003. View

14.

Hussain A, Lee R, Graff J, Halabi S . The evolution and understanding of skeletal complication endpoints in clinical trials of tumors with metastasis to the bone. Crit Rev Oncol Hematol. 2019; 139:108-116. PMC: 6609290. DOI: 10.1016/j.critrevonc.2019.04.020. View

15.

Kanda Y . Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2012; 48(3):452-8. PMC: 3590441. DOI: 10.1038/bmt.2012.244. View

16.

Akamatsu H, Ninomiya K, Kenmotsu H, Morise M, Daga H, Goto Y . The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV. Int J Clin Oncol. 2019; 24(7):731-770. PMC: 6545178. DOI: 10.1007/s10147-019-01431-z. View

17.

Inoue A, Kobayashi K, Usui K, Maemondo M, Okinaga S, Mikami I . First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol. 2009; 27(9):1394-400. DOI: 10.1200/JCO.2008.18.7658. View

18.

Iwama E, Goto Y, Murakami H, Harada T, Tsumura S, Sakashita H . Alectinib for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status (Lung Oncology Group in Kyushu 1401). J Thorac Oncol. 2017; 12(7):1161-1166. DOI: 10.1016/j.jtho.2017.02.012. View

19.

Yoshimura N, Muraki S, Oka H, Mabuchi A, En-yo Y, Yoshida M . Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study. J Bone Miner Metab. 2009; 27(5):620-8. DOI: 10.1007/s00774-009-0080-8. View

20.

Moore R, Doherty D, Chamberlain R, Khuri F . Sex differences in survival in non-small cell lung cancer patients 1974-1998. Acta Oncol. 2004; 43(1):57-64. View