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06.01.2021 | Original Article

Risk factors for skeletal-related events in non-small cell lung cancer patients treated with bone-modifying agents

verfasst von: Go Saito, Takahiro Ebata, Tsukasa Ishiwata, Shunichiro Iwasawa, Ichiro Yoshino, Yuichi Takiguchi, Koichiro Tatsumi

Erschienen in: Supportive Care in Cancer | Ausgabe 7/2021

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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.

Xu Z, Yang Q, Chen X, Zheng L, Zhang L, Yu Y, Chen M, You Q, Sun J (2019) Clinical associations and prognostic value of site-specific metastases in non-small cell lung cancer: a population-based study. Oncol Lett 17:5590–5600. https://doi.org/10.3892/ol.2019.10225CrossRefPubMedPubMedCentral

Tamura T, Kurishima K, Nakazawa K, Kagohashi K, Ishikawa H, Satoh H, Hizawa N (2015) Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol 3:217–221. https://doi.org/10.3892/mco.2014.410CrossRefPubMed

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

Santini D, Barni S, Intagliata S, Falcone A, Ferraù F, Galetta D, Moscetti L, La Verde N, Ibrahim T, Petrelli F, Vasile E, Ginocchi L, Ottaviani D, Longo F, Ortega C, Russo A, Badalamenti G, Collovà E, Lanzetta G, Mansueto G, Adamo V, De Marinis F, Satolli MA, Cantile F, Mancuso A, Tanca FM, Addeo R, Russano M, Sterpi M, Pantano F, Vincenzi B, Tonini G (2015) Natural history of non-small-cell lung cancer with bone metastases. Sci Rep 5:18670–18670. https://doi.org/10.1038/srep18670CrossRefPubMed

Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA, Schulman KA (2005) The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 16:579–584. https://doi.org/10.1093/annonc/mdi122CrossRefPubMed

Kunikane H, Yokota I, Katakami N, Takeda K, Takayama K, Sawa T, Saito H, Harada M, Yokota S, Ando K, Saito Y, Ohashi Y, Eguchi K (2019) Prospective analysis of the association between skeletal-related events and quality of life in patients with advanced lung cancer (CSP-HOR13). Oncol Lett 17:1320–1326. https://doi.org/10.3892/ol.2018.9680CrossRefPubMed

Kong P, Yan J, Liu D, Ji Y, Wang Y, Zhuang J, Wang J, Hu X, Yue X (2017) Skeletal-related events and overall survival of patients with bone metastasis from nonsmall cell lung cancer - a retrospective analysis. Medicine (Baltimore) 96:e9327–e9327. https://doi.org/10.1097/MD.0000000000009327CrossRef

D’Oronzo S, Coleman R, Brown J, Silvestris F (2018) Metastatic bone disease: pathogenesis and therapeutic options: up-date on bone metastasis management. J Bone Oncol 15:100205. https://doi.org/10.1016/j.jbo.2018.10.004CrossRef

Bongiovanni A, Recine F, Fausti V, Foca F, Casadei R, Falasconi MC, Oboldi D, Sansoni E, Fabbri L, Micheletti S, Severi S, Matteucci F, Zavoiu V, Mercatali L, Amadori D, Ibrahim T (2019) Ten-year experience of the multidisciplinary Osteoncology Center. Support Care Cancer 27:3395–3402CrossRefPubMed

10.

Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, Reitsma D, Seaman J (2004) 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 100:2613–2621. https://doi.org/10.1002/cncr.20308CrossRefPubMed

11.

Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H (2011) 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 29:1125–1132. https://doi.org/10.1200/JCO.2010.31.3304CrossRefPubMed

12.

Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, Peters S (2018) Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29:iv192–iv237. https://doi.org/10.1093/annonc/mdy275/CrossRefPubMed

13.

Lutz S, Balboni T, Jones J, Lo S, Petit J, Rich SE, Wong R, Hahn C (2017) Palliative radiation therapy for bone metastases: update of an ASTRO Evidence-Based Guideline Practical Radiation. Oncology 7:4–12. https://doi.org/10.1016/j.prro.2016.08.001CrossRef

14.

Ettinger DS, Wood DE, Aisner DL et al (2020) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Non-Small Cell Lung Cancer Version 3.2020-February 11, 2020. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Acceced 3 March 2020

15.

Nakahara Y, Hosomi Y, Shibuya M, Mitsufuji H, Katagiri M, Naoki K, Soejima K, Nogami N, Nagase S, Nishikawa M, Minato K, Takiguchi Y, Seki N, Yamada K, Seto T, Okamoto H (2019) 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 11:349–353. https://doi.org/10.3892/mco.2019.1903CrossRefPubMedPubMedCentral

16.

Sekine I, Nokihara H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T (2009) Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy. Lung Cancer 65:219–222. https://doi.org/10.1016/j.lungcan.2008.10.026CrossRefPubMed

17.

Sun J-M, Ahn JS, Lee S, Kim JA, Lee J, Park YH, Park HC, Ahn M-J, Ahn YC, Park K (2011) Predictors of skeletal-related events in non-small cell lung cancer patients with bone metastases. Lung Cancer 71:89–93. https://doi.org/10.1016/j.lungcan.2010.04.003CrossRefPubMed

18.

Hussain A, Lee RJ, Graff JN, Halabi S (2019) The evolution and understanding of skeletal complication endpoints in clinical trials of tumors with metastasis to the bone. Crit Rev Oncol Hematol 139:108–116. https://doi.org/10.1016/j.critrevonc.2019.04.020CrossRefPubMedPubMedCentral

19.

Kanda Y (2013) Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244CrossRefPubMed

20.

Akamatsu H, Ninomiya K, Kenmotsu H, Morise M, Daga H, Goto Y, Kozuki T, Miura S, Sasaki T, Tamiya A, Teraoka S, Tsubata Y, Yoshioka H, Hattori Y, Immamura CK, Katsuya Y, Matsui R, Mineishi Y, Mizugaki H, Nosaki K, Okuma Y, Sakamoto S, Sone T, Tanaka K, Umemura S, Yamanaka T, Amano S, Hasegawa K, Morita S, Nakajima K, Maemondo M, Seto T, Yamamoto N (2019) The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV. Int J Clin Oncol 24:731–770. https://doi.org/10.1007/s10147-019-01431-zCrossRefPubMedPubMedCentral

21.

Inoue A, Kobayashi K, Usui K, Maemondo M, Okinaga S, Mikami I, Ando M, Yamazaki K, Saijo Y, Gemma A, Miyazawa H, Tanaka T, Ikebuchi K, Nukiwa T, Morita S, Hagiwara K, North East Japan Gefitinib Study G (2009) 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 27:1394–1400. https://doi.org/10.1200/JCO.2008.18.7658CrossRefPubMed

22.

Iwama E, Goto Y, Murakami H, Harada T, Tsumura S, Sakashita H, Mori Y, Nakagaki N, Fujita Y, Seike M, Bessho A, Ono M, Okazaki A, Akamatsu H, Morinaga R, Ushijima S, Shimose T, Tokunaga S, Hamada A, Yamamoto N, Nakanishi Y, Sugio K, Okamoto I (2017) 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 12:1161–1166. https://doi.org/10.1016/j.jtho.2017.02.012CrossRefPubMed

23.

Yoshimura N, Muraki S, Oka H, Mabuchi A, En-Yo Y, Yoshida M, Saika A, Yoshida H, Suzuki T, Yamamoto S, Ishibashi H, Kawaguchi H, Nakamura K, Akune T (2009) 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 27:620–628. https://doi.org/10.1007/s00774-009-0080-8CrossRefPubMed

24.

Tian L, Yang R, Wei L, Liu J, Yang Y, Shao F, Ma W, Li T, Wang Y, Guo T (2017) Prevalence of osteoporosis and related lifestyle and metabolic factors of postmenopausal women and elderly men: a cross-sectional study in Gansu province, Northwestern of China. Medicine (Baltimore) 96:e8294–e8294. https://doi.org/10.1097/MD.0000000000008294CrossRef

25.

Moore R, Doherty D, Chamberlain R, Khuri F (2004) Sex differences in survival in non-small cell lung cancer patients 1974-1998. Acta Oncol 43:57–64. https://doi.org/10.1080/02841860310017973CrossRefPubMed

26.

Radkiewicz C, Dickman PW, Johansson ALV, Wagenius G, Edgren G, Lambe M (2019) Sex and survival in non-small cell lung cancer: a nationwide cohort study. PLoS One 14:e0219206. https://doi.org/10.1371/journal.pone.0219206CrossRefPubMedPubMedCentral

27.

Udagawa H, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Goto K (2017) Impact of denosumab use on the survival of untreated non-squamous non-small cell lung cancer patients with bone metastases. J Cancer Res Clin Oncol 143:1075–1082. https://doi.org/10.1007/s00432-017-2350-5CrossRefPubMed

28.

Peters S, Danson S, Hasan B, Dafni U, Reinmuth N, Majem M, Tournoy KG, Mark MT, Pless M, Cobo M, Rodriguez-Abreu D, Falchero L, Moran T, Granados A, Monnet I, Mohorcic K, Sureda BM, Betticher D, Demedts I, Macias JA, Cuffe S, Luciani A, Sanchez JG, Curioni-Fontecedro A, Gautschi O, Price G, Coate L, von Moos R, Zielinski C, Provencio M, Menis J, Ruepp B, Pochesci A, Roschitzki-Voser H, Besse B, Ragablio M, O’Brien M, Stahel RA (2020) A randomized open-label phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC: the European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial. J Thorac Oncol 15:1647–1656. https://doi.org/10.1016/j.jtho.2020.06.011CrossRefPubMed

29.

Qu X, Huang X, Yan W, Wu L, Dai K (2012) A meta-analysis of ¹⁸FDG-PET-CT, ¹⁸FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer. Eur J Radiol 81:1007–1015. https://doi.org/10.1016/j.ejrad.2011.01.126CrossRefPubMed

30.

Suga Y, Uchida M, Suzuki S, Sugawara H, Torigoe K, Futamura A, Uesawa Y, Nakagawa T, Takase H (2019) Current status of adverse events related with opioid analgesics in Japan: assessment based on Japanese Adverse Drug Event Report Database. Biol Pharm Bull 42:801–806. https://doi.org/10.1248/bpb.b18-00997CrossRefPubMed

31.

Chow E, Harris K, Fan G, Tsao M, Sze WM (2007) Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 25:1423–1436. https://doi.org/10.1200/JCO.2006.09.5281CrossRefPubMed

32.

Middleton G, Brock K, Summers Y, Connibear J, Shah R, Ottensmeier C, Shaw P, Ming-Lee S, Popat S, Barrie C, Barone G, Mant R, Savage JS, Billingham L (2018) Pembrolizumab in performance status 2 patients with non-small cell lung cancer (NSCLC): results of the PePS2 trial. Ann Oncol 29:viii497. https://doi.org/10.1093/annonc/mdy292.007CrossRef

33.

Felip E, Ardizzoni A, Ciuleanu T, Cobo M, Laktionov K, Szilasi M, Califano R, Carcereny E, Griffiths R, Paz-Ares L, Duchnowska R, Garcia MA, Isla D, Jassem J, Appel W, Milanowski J, Van Meerbeeck JP, Wolf J, Li A, Acevedo A, Popat S (2020) CheckMate 171: a phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations. Eur J Cancer 127:160–172. https://doi.org/10.1016/j.ejca.2019.11.019CrossRefPubMed

Titel: Risk factors for skeletal-related events in non-small cell lung cancer patients treated with bone-modifying agents
verfasst von: Go Saito
Takahiro Ebata
Tsukasa Ishiwata
Shunichiro Iwasawa
Ichiro Yoshino
Yuichi Takiguchi
Koichiro Tatsumi
Publikationsdatum: 06.01.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Supportive Care in Cancer / Ausgabe 7/2021
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-020-05880-5

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Risk factors for skeletal-related events in non-small cell lung cancer patients treated with bone-modifying agents