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骨转移是肿瘤晚期的常见并发症,特别是前列腺、乳腺和肺部的肿瘤[1]。骨转移患者由于严重的疼痛往往导致生活质量下降,且易出现与骨骼相关的不良事件,如病理性骨折、脊髓压迫和高钙血症等。针对骨转移疼痛的治疗通常包括常规止痛、镇痛和外部照射放疗[2]。轻、中度和局限性的骨痛可以根据世界卫生组织疼痛阶梯方案使用止痛药[3]。持续性、较严重的疼痛可以采取外部放疗。然而,外部放疗由于重复使用后会引起骨髓和胃肠道放射性不良反应的累积、不能适用于全身多处转移的情况,临床应用受到限制。
某些放射性核素能够特异性地被活性增高的成骨细胞摄取,并且能较长时间滞留于骨组织中。因此,使用骨靶向性的放射性核素进行系统性的治疗成为另一种替代方式,特别是对于那些存在广泛骨转移的患者,该方法在临床上的使用已经超过30余年。目前,对于前列腺癌骨转移的放射性核素治疗已经相当成熟,其不良反应小、耐受性好[4],而其他类型的肿瘤临床证据则相对较少[5]。
Cochrane循证医学协作网提供的一项研究证据表明,放射性同位素治疗能够缓解转移性骨痛对不同类型的肿瘤并没有区别,一些新型的骨靶向放射性核素(如89Sr、153Sm、186Re等)已被用于治疗肺癌骨转移导致的疼痛[6]。笔者就骨靶向放射性核素治疗肺癌骨转移疼痛的临床研究进行综述。
骨靶向放射性核素治疗肺癌骨转移疼痛的研究进展
Research progress in bone-targeting radionuclides in the treatment of bone metastases from lung cancer
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摘要: 肺癌骨转移是肿瘤晚期的常见并发症,患者由于严重的疼痛往往导致生活质量下降,且易出现与骨骼相关的不良事件,如病理性骨折、脊髓压迫和高钙血症等。针对轻、中度骨转移引起的疼痛可以采用常规止痛、镇痛和外部照射放疗。但在全身多处转移和疼痛严重的情况下,以上3种方法的疗效都不好,且不良反应严重。而某些放射性核素能够特异性地被活性增高的成骨细胞摄取,并且能较长时间滞留于骨组织中。因此,使用一些新型骨靶向放射性核素,如89Sr、153Sm和186Re等进行系统性的治疗成为新型方式,为肺癌骨转移疼痛的治疗提供了更多的靶点和安全有效的手段。Abstract: Bone metastasis is a common complication of advanced tumors. Severe pain frequently leads to a decline in quality of life and tendency toward bone-related adverse events, such as pathological fractures, spinal cord compression, and hypercalcemia. To alleviate pain caused by mild to moderate bone metastases, conventional analgesic or external radiation therapy can be used. However, when multiple body metastases and severe pain occur, the two aforementioned methods become ineffective and cause serious side effects. Some radionuclides can be specifically taken up by activated osteoblasts and can be retained in bone tissues for a long time. Therefore, systematic treatment with several new bone-targeting radionuclides, such as 89Sr, 153Sm, and 186Re, has become a new approach for providing additional targets and a safe and effective treatment for bone metastases.
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Key words:
- Lung neoplasms /
- Radionuclide therapy /
- Pain /
- Bone metastases
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[1] Isaac A, Dalili D, Daniel D, et al. State-of-the-art imaging for diagnosis of metastatic bone disease[J/OL]. Der Radiologe, 2020[2020-03-24]. https://link.springer.com/article/10.1007/s00117-020-00666-6. [published online ahead of print March 24, 2020]. DOI: 10.1007/s00117−020−00666−6. [2] Weller D, Bamias, A. Bone health in cancer patients–An important clinical issue[J/OL]. Eur J Cancer Care (Engl), 2017, 26(6): e12791[2019-01-28]. 10.1111/ecc.12791">https://onlinelibrary.wiley.com/doi/full/10.1111/ecc.12791. DOI: 10.1111/ecc.12791. [3] WHO. WHO Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents[EB/OL]. (2019-01)[2019-01-28]. https://www.who.int/ncds/management/palliative-care/cancer-pain-guidelines/en/. [4] Goyal J, Antonarakis ES. Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases[J]. Cancer Lett, 2012, 323(2): 135−146. DOI: 10.1016/j.canlet.2012.04.001. [5] Hojjat A, Markus E, Kambiz R, et al. Radionuclide Therapy for Bone Metastases: Utility of Scintigraphy and PET Imaging for Treatment Planning[J]. PET Clin, 2018, 13(4): 491−503. DOI: 10.1016/j.cpet.2018.05.005. [6] Roqué I Figuls M, Martinez-Zapata MJ, Scott-Brown M, et al. Radioisotopes for metastatic bone pain[J/OL]. Cochrane Database Syst Rev, 2011, 6(7): CD003347[2019-01-28]. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003347.pub2/full. DOI: 10.1002/14651858.CD003347.pub2. [7] 匡安仁, 李林. 核医学[M]. 2版. 北京: 高等教育出版社, 2017: 266−271.
Kuang AR, Li L. Nuclear medicine[M]. 2nd ed. Beijing: Higher Education Press, 2017: 266−271.[8] Heianna J, Miyauchi T, Endo WM, et al. Tumor regression of multiple bone metastases from breast cancer after administration of strontium-89 chloride (Metastron)[J/OL]. Acta Radiol Short Rep, 2014, 3(4): 2047981613493412[2019-01-28]. https://journals.sagepub.com/doi/10.1177/2047981613493412. DOI: 10.1177/2047981613493412. [9] 中华医学会核医学分会转移性骨肿瘤治疗工作委员会. 氯化锶[89Sr]治疗转移性骨肿瘤专家共识(2017年版)[J]. 中华核医学与分子影像杂志, 2018, 38(6): 412−415. DOI: 10.3760/cma.j.issn.2095-2848.2018.06.008.
The Chinese Society of Nuclear Medicine Working Committee for Treatment of Bone Metastasis. Expert consensus on strontium-89 chloride treatment of bone metastases (2017)[J]. Chin J Nucl Med Mol Imaging, 2018, 38(6): 412−415. DOI: 10.3760/cma.j.issn.2095-2848.2018.06.008.[10] 耿向群. 89-锶治疗肺癌骨转移的临床疗效分析[J]. 中国医学创新, 2013, 10(33): 21−22. DOI: 10.3969/j.issn.1674-4985.2013.33.010.
Geng XQ. Clinical Analysis of 89-SR Treatment on Bone Metastasis on Lung Cancer[J]. Med Inn China, 2013, 10(33): 21−22. DOI: 10.3969/j.issn.1674-4985.2013.33.010.[11] 范义湘, 罗荣城, 李贵平, 等. 89Sr治疗肺癌骨转移疼痛65例疗效分析[J]. 中国临床康复, 2004, 8(5): 812−813. DOI: 10.3321/j.issn:1673-8225.2004.05.007.
Fan YX, Luo RC, Li GP, et al. Antalgic effects of strontium-89 therapy on bone metastases in 65 patients with lung cancer[J]. Chin J Clin Rehabil, 2004, 8(5): 812−813. DOI: 10.3321/j.issn:1673-8225.2004.05.007.[12] 郑航, 罗荣城, 范义湘. 89SrCl2治疗肺癌骨转移126例疗效分析[J]. 第一军医大学学报, 2004, 24(10): 1194−1196. DOI: 10.3321/j.issn:1673-4254.2004.10.028.
Zheng H, Luo RC, Fan YX. Therapeutic effects of 89SrCl2 against osseous metastases of lung cancer: analysis of 126 cases[J]. J First Mil Med Univ, 2004, 24(10): 1194−1196. DOI: 10.3321/j.issn:1673-4254.2004.10.028.[13] 胥杰, 陈晓 . 89Sr治疗30例肺癌多发骨转移的疗效观察[J]. 中国呼吸与危重监护杂志, 2008, 7(2): 104−106. DOI: 10.3969/j.issn.1671-6205.2008.02.006.
Xu J, Chen X. Therapeutic effects of strontium-89 to prevent bone metastases of lung cancer: A clinical analysis of 30 cases[J]. Chin J Respir Crit Care Med, 2008, 7(2): 104−106. DOI: 10.3969/j.issn.1671-6205.2008.02.006.[14] D' Antonio C, Passaro A, Gori B, et al. Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies[J]. Ther Adv Med Oncol, 2014, 6(3): 101−114. DOI: 10.1177/1758834014521110. [15] Lange R, Ter Heine R, Knapp RF, et al. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases[J]. Bone, 2016, 91: 159−179. DOI: 10.1016/j.bone.2016.08.002. [16] 李宁, 杨志, 柴华, 等. 唑来膦酸联合89Sr治疗无症状非小细胞肺癌骨转移临床研究[J]. 中华肿瘤防治杂志, 2018, 25(13): 962−967. DOI: 10.16073/j.cnki.cjcpt.2018.13.009.
Li N, Yang Z, Chai H, et al. Clinical research of zoledronic acid and strontium-89 in treatment of patients with asymptomatic bone metastases from non-small cell lung cancer[J]. Chin J Cancer Prev Treat, 2018, 25(13): 962−967. DOI: 10.16073/j.cnki.cjcpt.2018.13.009.[17] 李梅, 王火强. 89SrCl2联合伊班膦酸钠对肺癌骨转移骨痛的疗效分析[J]. 放射免疫学杂志, 2013, 26(4): 390−392. DOI: 10.3969/j.issn.1008-9810.2013.04.003.
Li M, Wang HQ. Therapeutic efficacy of 89SrCl2 combined with ibandronate in the treatment of osseous metastasis of lung cancer[J]. J Radioimmunol, 2013, 26(4): 390−392. DOI: 10.3969/j.issn.1008-9810.2013.04.003.[18] 梁忠, 于珺, 李雨林. 89锶和博宁治疗非小细胞肺癌骨转移87例疗效观察[J]. 第四军医大学学报, 2007, 28(19): 1737. DOI: 10.3321/j.issn:1000-2790.2007.19.031.
Liang Z, Yu J, Li YL. Clinical observation of 87 cases of bone metastasis from non-small cell lung cancer treated with strontium-89 and bonin[J]. J Fourth Mil Med Univ, 2007, 28(19): 1737. DOI: 10.3321/j.issn:1000-2790.2007.19.031.[19] 董占飞, 秦永德, 王新华. 89SrCl2联合99Tc-MDP或唑来膦酸治疗肺癌骨转移疼痛的临床疗效观察[J]. 中国肿瘤临床, 2012, 39(21): 1660−1662. DOI: 10.3969/j.issn.1000-8179.2012.21.024.
Dong ZF, Qin YD, Wang XH. Clinical observation of internal radiotherapy using 89Sr 99Tc-MDP and Zoledronic acid in the treatment and pain relief of lung cancer patients with bone metastasis[J]. Chin J Clin Oncol, 2012, 39(21): 1660−1662. DOI: 10.3969/j.issn.1000-8179.2012.21.024.[20] 苏瑾, 尤长宣, 蔡绍曦, 等. 89SrCl2和/或骨膦治疗肺癌骨转移疗效分析[J]. 中国肺癌杂志, 2002, 5(5): 357−359. DOI: 10.3779/j.issn.1009-3419.2002.05.11.
Su J, You CX, Cai SX, et al. 89SrCl2 and/Or Bonefos in the treatment of bone metastasis from pulmonary carcinoma[J]. Chin J Lung Cancer, 2002, 5(5): 357−359. DOI: 10.3779/j.issn.1009-3419.2002.05.11.[21] 邵珊珊, 李鹏, 张良明. 锶89与放疗在非小细胞肺癌骨转移骨痛治疗中的疗效比较[J]. 中国医药科学, 2014, 4(5): 22−24.
Shao SS, Li P, Zhang LM. A comparison of curative effects of Strontium 89 and radiotherapy in the treatment of bone metastasis and ostealgia induced by non-small cell lung cancer[J]. China Med Pharm, 2014, 4(5): 22−24.[22] 张云平, 江敏霞, 蔡奋, 等. 89锶联合鲑鱼降钙素治疗肺癌骨转移骨痛的疗效观察[J]. 汕头大学医学院学报, 2016, 29(3): 148−149. DOI: 10.13401/j.cnki.jsumc.2016.03.008.
Zhang YP, Jiang MX, Cai F, et al. Clinical observation of 89Sr combined with salmon calcitonin in the treatment of bone metastasis and pain of lung cancer[J]. J Shantou Univ Med Coll, 2016, 29(3): 148−149. DOI: 10.13401/j.cnki.jsumc.2016.03.008.[23] 刘江, 赵颖如, 徐文贵. 放射性核素钐153的应用进展[J]. 国际医学放射学杂志, 2014, 37(4): 366−370. DOI: 10.3874/j.issn.1674-1897.2014.04.Z0412.
Liu J, Zhao YR, Xu WG. Application progress of radionuclide Samarium-153[J]. Int J Med Radiol, 2014, 37(4): 366−370. DOI: 10.3874/j.issn.1674-1897.2014.04.Z0412.[24] Farhanghi M, Holmes RA, Volkert WA, et al. Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer[J]. J Nucl Med, 1992, 33(8): 1451−1458. [25] Guerra Liberal FDC, Tavares AAS, Tavares JMRS. Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153[J]. Appl Radiat Isot, 2016, 110: 87−99. DOI: 10.1016/j.apradiso.2016.01.003. [26] Ratsimanohatra H, Barlesi F, Doddoli C, et al. Use of 153Sm-EDTMP to relieve pain from bone metastasis in lung cancer[J]. Rev Mal Respir, 2005, 22(2): 317−320. DOI: 10.1016/S0761-8425(05)85484-1. [27] 王水利, 吴桦, 王勇文, 等. 153Sm-EDTMP对肺癌并骨转移治疗价值的探讨[J]. 中国现代医学杂志, 2002, 12(2): 92−93. DOI: 10.3969/j.issn.1005-8982.2002.02.044.
Wang SL, Wu H, Wang YW, et al. Discussion of 153Sm-EDTMP in the treatment of lung cancer complicated with bone metastases[J]. China J Mod Med, 2002, 12(2): 92−93. DOI: 10.3969/j.issn.1005-8982.2002.02.044.[28] 舒斌, 徐蓉生, 段云, 等. 153Sm-EDTMP对小细胞肺癌与非小细胞肺癌骨转移的止痛疗效观察[J]. 华西医学, 2004, 19(2): 201−202. DOI: 10.3969/j.issn.1002-0179.2004.02.015.
Shu B, Xu RS, Duan Y, et al. Clinical observation of 153Sm-EDTMP as a palliative treatment for small cell lung cancer and non-small cell lung cancer patient with painful bone metastasis[J]. West China Med J, 2004, 19(2): 201−202. DOI: 10.3969/j.issn.1002-0179.2004.02.015.[29] Montesano T, Giacomobono S, Acqualagna G, et al. Our experience on pain palliation of bone metastasis with Sr-89 or Sm-153 in cancer patients resistant to a conventional analgesic therapy. A retrospective study[J]. Clin Ter, 2009, 160(3): 193−199. [30] 李少民, 王永亮, 李淳成. 核素、博宁及化疗治疗骨转移疼痛疗效分析[J]. 肿瘤研究与临床, 1999, 11(1): 45−46.
Li SM, Wang YL, Li CC. Therapeutic effect of radionuclide, Bonin and chemotherapy on bone metastasis pain[J]. Cancer Res Clin, 1999, 11(1): 45−46.[31] Haase AA , Bauer EB, Kühn FE. et al Speciation and toxicity of rhenium salts, organometallics and coordination complexes[J]. Coord Chem Rev, 2019, 394: 135−161. DOI: 10.1016/j.ccr.2019.05.012. [32] Leondi AH, Souvatzoglou MA, Rapti AS, et al. Palliative treatment of painful disseminated bone metastases with 186Rhenium-HEDP in patients with lung cancer[J]. Q J Nucl Med Mol Imaging, 2004, 48(3): 211−219. [33] Minutoli F, Herberg A, Spadaro P, et al. [186Re]HEDP in the palliation of painful bone metastases from cancers other than prostate and breast[J]. Q J Nucl Med Mol Imaging, 2006, 50(4): 355−362. [34] Küçük NÖ, İbiş E, Aras G, et al. Palliative analgesic effect of Re-186 HEDP in various cancer patients with bone metastases[J]. Ann Nucl Med, 2000, 14(4): 239−245. DOI: 10.1007/bf02988205. [35] 孙燕, 管忠震, 廖美琳, 等. 肺癌骨转移诊疗专家共识(2014版)[J]. 中国肺癌杂志, 2014, 17(2): 57−72. DOI: 10.3779/j.issn.1009-3419.2014.02.01.
Sun Y, Guan ZZ, Liao ML, et al. Expert Consensus on the Diagnosis and Treatment of Bone Metastasis in Lung Cancer (2014 version)[J]. Chin J Lung Cancer, 2014, 17(2): 57−72. DOI: 10.3779/j.issn.1009-3419.2014.02.01.
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