肺癌骨转移治疗的研究进展

doi:10.3760/cma.j.cn371439-20240608-00134

摘要/Abstract

摘要：

肺癌骨转移在晚期肺癌患者中较为常见，其治疗研究取得了显著进展。全身治疗方面，化疗是传统的治疗方案；靶向治疗针对特定基因突变的肺癌患者展现出强大的疗效；免疫治疗可通过激活机体免疫系统，为肺癌骨转移患者带来新的治疗选择，可单独应用或与其他疗法联合。抗骨转移药物如双膦酸盐和地舒单抗在减少骨破坏及骨相关不良事件方面发挥重要作用。局部治疗方面，放疗可精准照射肿瘤病灶，缓解疼痛症状；手术治疗适用于特定的骨转移病灶，恢复骨骼稳定性和功能。此外，镇痛治疗和心理干预可缓解患者的疼痛和焦虑。这些治疗研究进展为肺癌骨转移患者带来新的希望。

关键词: 肺肿瘤, 肿瘤转移, 治疗

Abstract:

Bone metastasis of lung cancer is relatively common in patients with advanced lung cancer， the treatment research of which has been made remarkable progress. In terms of systemic therapy， chemotherapy is the traditional treatment plan； targeted therapy shows strong efficacy in treating lung cancer patients with specific gene mutations； immunotherapy can bring new treatment options for lung cancer patients with bone metastasis by activating the body's immune system， which can be used alone or in combination with other therapies. Anti bone metastasis drugs such as bisphosphonates and denosumab play an important role in reducing bone destruction and bone-related adverse events. In terms of local therapy， radiotherapy can accurately irradiate tumor lesions and relieve pain symptoms； surgical treatment is suitable for specific bone metastasis to restore bone stability and function. In addition， analgesic treatment and psychological intervention can alleviate patients' pain and anxiety. These therapeutic advances bring new hope to patients with lung cancer bone metastasis.

Key words: Lung neoplasms, Neoplasm metastasis, Therapy

于德刚, 贾军梅. 肺癌骨转移治疗的研究进展[J]. 国际肿瘤学杂志, 2024, 51(12): 789-793.

Yu Degang, Jia Junmei. Research progress in the treatment of bone metastasis in lung cancer[J]. Journal of International Oncology, 2024, 51(12): 789-793.

参考文献 37

[1]	支修益, 王洁, 刘伦旭, 等. 中国肺癌骨转移临床诊疗指南(2024版)[J]. 中国胸心血管外科临床杂志, 2024, 31(5): 643-653. DOI: 10.7507/1007-4848.202402042.
[2]	Bessa CMD, Silva LMD, Zamboni MM, et al. Bone metastasis after stage ⅢA non-small cell lung cancer: risks and prognosis[J]. J Bras Pneumol, 2022, 48(5): e20220211. DOI: 10.36416/1806-3756/e20220211.
[3]	Coleman R. Bone-targeted agents and metastasis prevention[J]. Cancers(Basel), 2022, 14(15): 3640. DOI: 10.3390/cancers14153640.
[4]	Li B, Wang P, Jiao J, et al. Roles of the RANKL-RANK axis in immunity-implications for pathogenesis and treatment of bone metastasis[J]. Front Immunol, 2022, 13: 824117. DOI: 10.3389/fimmu.2022.824117.
[5]	Wu MY, Li CJ, Yiang GT, et al. Molecular regulation of bone metastasis pathogenesis[J]. Cell Physiol Biochem, 2018, 46(4): 1423-1438. DOI: 10.1159/000489184.
[6]	Nistor CE, Ciuche A, Cucu AP, et al. Management of lung cancer presenting with solitary bone metastasis[J]. Medicina (Kaunas), 2022, 58(10): 1463. DOI: 10.3390/medicina58101463.
[7]	Soo RA, Reungwetwattana T, Perroud HA, et al. Prevalence of EGFR mutations in patients with resected stages Ⅰ to Ⅲ NSCLC: results from the EARLY-EGFR study[J]. J Thorac Oncol, 2024, 19(10): 1449-1459. DOI: 10.1016/j.jtho.2024.06.008.
[8]	Kuijpers CCHJ, Hendriks LEL, Derks JL, et al. Association of molecular status and metastatic organs at diagnosis in patients with stage Ⅳ non-squamous non-small cell lung cancer[J]. Lung Cancer, 2018, 121: 76-81. DOI: 10.1016/j.lungcan.2018.05.006. pmid: 29858031
[9]	Miyagi M, Katagiri H, Murata H, et al. Osteosclerotic change as a therapeutic response to gefitinib in symptomatic non-small cell lung cancer bone metastasis[J]. BMC Pulm Med, 2022, 22(1): 491. DOI: 10.1186/s12890-022-02226-1.
[10]	Kanaoka K, Sumikawa H, Oyamada S, et al. Osteoblastic bone reaction in non-small cell lung cancer harboring epidermal growth factor receptor mutation treated with osimertinib[J]. BMC Cancer, 2023, 23(1): 834. DOI: 10.1186/s12885-023-11360-w.
[11]	Higuchi T, Sugisawa N, Park JH, et al. Osimertinib regressed an EGFR-mutant lung-adenocarcinoma bone-metastasis mouse model and increased long-term survival[J]. Transl Oncol, 2020, 13(10): 100826. DOI: 10.1016/j.tranon.2020.100826.
[12]	Zhang G, Cheng R, Zhang Z, et al. Bisphosphonates enhance antitumor effect of EGFR-TKIs in patients with advanced EGFR mutant NSCLC and bone metastases[J]. Sci Rep, 2017, 7: 42979. DOI: 10.1038/srep42979. pmid: 28211502
[13]	Ko HW, Chiu CT, Wang CL, et al. Overall survival improvement in patients with epidermal growth factor receptor-mutated non-small cell lung cancer and bone metastasis treated with denosumab[J]. Cancers(Basel), 2022, 14(14): 3470. DOI: 10.3390/cancers14143470.
[14]	Asano Y, Yamamoto N, Demura S, et al. The therapeutic effect and clinical outcome of immune checkpoint inhibitors on bone metastasis in advanced non-small-cell lung cancer[J]. Front Oncol, 2022, 12: 871675. DOI: 10.3389/fonc.2022.871675.
[15]	Del Conte A, De Carlo E, Bertoli E, et al. Bone metastasis and immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): microenvironment and possible clinical implications[J]. Int J Mol Sci, 2022, 23(12): 6832. DOI: 10.3390/ijms23126832.
[16]	Li HS, Lei SY, Li JL, et al. Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: a retrospective chart review[J]. Front Immunol, 2022, 13: 908436. DOI: 10.3389/fimmu.2022.908436.
[17]	Xie X, Zhou M, Wang L, et al. Effects of combining immune checkpoint inhibitors and anti-angiogenic agents on bone metastasis in non-small cell lung cancer patients[J]. Hum Vaccin Immunother, 2023, 9(2): 2241310. DOI: 10.1080/21645515.2023.2241310.
[18]	Zheng Y, Wang PP, Fu Y, et al. Zoledronic acid enhances the efficacy of immunotherapy in non-small cell lung cancer[J]. Int Immunopharmacol, 2022, 110: 109030. DOI: 10.1016/j.intimp.2022.109030.
[19]	Zhu YJ, Chang XS, Zhou R, et al. Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays "cold" immune characteristics in non-small cell lung cancer[J]. Lung Cancer, 2022, 166: 189-196. DOI: 10.1016/j.lungcan.2022.03.006.Epub.
[20]	Clézardin P, Coleman R, Puppo M, et al. Bone metastasis: mechanisms, therapies, and biomarkers[J]. Physiol Rev, 2021, 101(3): 797-855. DOI: 10.1152/physrev.00012.2019.
[21]	Wu S, Pan Y, Mao Y, et al. Current progress and mechanisms of bone metastasis in lung cancer: a narrative review[J]. Transl Lung Cancer Res, 2021, 10(1): 439-451. DOI: 10.21037/tlcr-20-835.
[22]	Wang L, Fang D, Xu J, et al. Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review[J]. BMC Cancer, 2020, 20(1): 1059. DOI: 10.1186/s12885-020-07568-9.
[23]	Nakahara Y, Hosomi Y, Shibuya M, et al. Multicenter study of zoledronic acid administration in non-small-cell lung cancer patients with bone metastasis: Thoracic Oncology Research Group (TORG) 1017[J]. Mol Clin Oncol, 2019, 11(4): 349-353. DOI: 10.3892/mco.2019.1903. pmid: 31475062
[24]	Zhang J, Yu L, Guan J, et al. Zoledronic acid combined with chemotherapy in non-small cell lung cancer with bone metastasis[J]. J BUON, 2021, 26(3): 830-836. pmid: 34268942
[25]	Lu J, Hu D, Zhang Y, et al. Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials[J]. Front Oncol, 2023, 13: 1133828. DOI: 10.3389/fonc.2023.1133828.
[26]	Cadieux B, Coleman R, Jafarinasabian P, et al. Experience with denosumab (XGEVA^®) for prevention of skeletal-related events in the 10 years after approval[J]. J Bone Oncol, 2022, 33: 100416. DOI: 10.1016/j.jbo.2022.100416.
[27]	De Castro J, García R, Garrido P, et al. Therapeutic potential of denosumab in patients with lung cancer: beyond prevention of skeletal complications[J]. Clin Lung Cancer, 2015, 16(6): 431-446. DOI: 10.1016/j.cllc.2015.06.004. pmid: 26264596
[28]	Niu X, Wei F, Tu C, et al. Efficacy and safety of JMT103 in patients with giant cell tumor of bone: a multicenter, single-arm, open label, phase Ⅰb /Ⅱ study[J]. J Clin Oncol, 2021, 39(15_ suppl): 11526-11526. DOI: 10.1200/JCO.2021.39.15_suppl.11526.
[29]	Tian D, Ben X, Wang S, et al. Surgical resection of primary tumors improved the prognosis of patients with bone metastasis of non-small cell lung cancer: a population-based and propensity score-matched study[J]. Ann Transl Med, 2021, 9(9): 775. DOI: 10.21037/atm-21-540.
[30]	Makita K, Hamamoto Y, Kanzaki H, et al. Local control of bone metastasis treated with palliative radiotherapy in patients with lung cancer: an observational retrospective cohort study[J]. Oncol Lett, 2023, 26(1): 303. DOI: 10.3892/ol.2023.13889.
[31]	De Felice F, Piccioli A, Musio D, et al. The role of radiation therapy in bone metastases management[J]. Oncotarget, 2017, 8(15): 25691-25699. DOI: 10.18632/oncotarget.14823. pmid: 28148890
[32]	王培伟, 翁一鸣, 崔雪, 等. 免疫检查点抑制剂联合放疗在非小细胞肺癌中的应用[J]. 国际肿瘤学杂志, 2021, 48(11): 678-682. DOI: 10.3760/cma.j.cn371439-20210126-00134.
[33]	Cui J, Li L, Yuan S. The value of radiotherapy for advanced non-small cell lung cancer with oncogene driver-mutation[J]. Front Oncol, 2022, 12: 863715. DOI: 10.3389/fonc.2022.863715.
[34]	郭连洪, 赵素花, 李斌, 等. 大剂量和常规分割剂量调强适形放疗联合⁸⁹SrCl₂静脉注射治疗肺癌骨转移的效果[J]. 中国医学物理学杂志, 2020, 37(9): 1111-1114. DOI: 10.3969/j.issn.1005-202X.2020.09.006.
[35]	Wong HCY, Chan AW, Johnstone P, et al. A critical appraisal of the four systematic reviews and meta-analysis on stereotactic body radiation therapy versus external beam radiotherapy for painful bone metastases and where we go from here[J]. Ann Palliat Med, 2023, 12(6): 1318-1330. DOI: 10.21037/apm-23-218.
[36]	豆丽园, 蒋秋玲, 申文佳, 等. 晚期肺癌患者疼痛危象发生现状及影响因素研究[J]. 中华护理杂志, 2024, 59(11): 1353-1359. DOI: 10.3761/j.issn.0254-1769.2024.11.010.
[37]	Xie J, Xu Y, Liu X, et al. Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles[J]. Elife, 2024, 12: RP89613. DOI: 10.7554/eLife.89613.