尼达尼布治疗放射性肺损伤一例并文献复习_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

张凌云 ¹ , 田飞 ² , 龚正 ¹ , 张敏 ¹ , 王玲 ¹ , 向军 ¹ , 王巍 ¹ , 陆志凌 ¹ , 向光明 ¹ ,  高宝安 ¹

1. ;
2. ;

Corresponding author：

高宝安, Email: springxiaozhu@163.com

Keywords：

尼达尼布; 放射性粒子; 放射性肺损伤; 疗效

DOI：

10.7507/1671-6205.202008044

Video：

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目的探讨放射性肺损伤的发病机制、临床表现、影像学特点、可能的治疗手段及预后。方法分析 1 例确诊为肺鳞癌合并放射性肺损伤并接受尼达尼布治疗患者的临床资料，结合相关文献复习，总结其临床特点、治疗过程及预后。结果本例为 72 岁男性肺鳞癌患者，经同步放化疗和放射性粒子植入术后并发放射性肺损伤，主要症状为活动后气促，胸部 CT 表现为双肺磨玻璃影和网格影，右下肺显著。经尼达尼布规范化治疗 4 个月后，临床症状以及影像学都明显缓解，随访 1 年，病情持续稳定，未见明显不良反应。文献复习发现，放射性肺损伤患者临床上多表现为干咳、发热及呼吸困难，重症患者可危及生命，影像学多表现为放射靶区的片状影，多以肺实变伴支气管充气征为主。最常用的治疗药物为糖皮质激素，也有少部分患者对激素治疗反应不佳，新的治疗手段仍在探索之中。结论放射性肺损伤是恶性肿瘤患者放疗过程中较常见的并发症，但目前治疗手段有限，尼达尼布作为一种新型的小分子靶向药，可能对放射性肺损伤具有一定的修复作用。

Citation： 张凌云, 田飞, 龚正, 张敏, 王玲, 向军, 王巍, 陆志凌, 向光明, 高宝安. 尼达尼布治疗放射性肺损伤一例并文献复习. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(8): 584-587. doi: 10.7507/1671-6205.202008044 Copy

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16.	Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med, 2019, 380(26): 2518-2528.
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18.	Capelletto E, Migliorino MR, Morabito A, et al. Final results of the SENECA (SEcond line NintEdanib in non-small cell lung CAncer) trial. Lung Cancer, 2019, 134: 210-217.
19.	Forster M, Hackshaw A, De Pas T, et al. A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3). Lung Cancer, 2018, 120: 27-33.
20.	Henkenberens C, Janssen S, Lavae-Mokhtari M, et al. Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade Ⅱ after radiotherapy - a single-centre experience. Radiat Oncol, 2016, 11: 12.
21.	Hanania AN, Mainwaring W, Ghebre YT, et al. Radiation-induced lung injury: assessment and management. Chest, 2019, 156(1): 150-162.
22.	Jackson IL, Vujaskovic Z, Down JD. A further comparison of pathologies after thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation-induced lung damage. Radiat Res, 2011, 175: 510-518.
23.	Otani K, Nishiyama K, Ito Y, et al. Steroid treatment increases the recurrence of radiation-induced organizing pneumonia after breast-conserving therapy. Cancer Med, 2014, 3(4): 947-953.
24.	Wollin L, Distler JHW, Redente EF, et al. Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases. Eur Respir J, 2019, 54(3): 1900161.
25.	Jin H, Yoo Y, Kim Y, et al. Radiation-induced lung fibrosis: preclinical animal models and therapeutic strategies. Cancers (Basel), 2020, 12(6): 1561.
26.	Westbury CB, Yarnold JR. Radiation fibrosis--current clinical and therapeutic perspectives. Clin Oncol (R Coll Radiol), 2012, 24(10): 657-672.
27.	刘文秀, 杨娟, 曹博, 等. 甲磺酸伊马替尼对放射性肺炎小鼠肺部氧化应激指标及转化生长因子-β1 表达影响的研究. 中国呼吸与危重监护杂志, 2017, 16(5): 446-450.
28.	De Ruysscher D, Granton PV, Lieuwes NG, et al. Nintedanib reduces radiation-induced microscopic lung fibrosis but this cannot be monitored by CT imaging: a preclinical study with a high precision image-guided irradiator. Radiother Oncol, 2017, 124(3): 482-487.

1. Bledsoe TJ, Nath SK, Decker RH. Radiation pneumonitis. Clin Chest Med, 2017, 38(2): 201-208.
2. Zhang P, Yan H, Wang S, et al. Post-radiotherapy maintenance treatment with fluticasone propionate and salmeterol for lung cancer patients with grade Ⅲ radiation pneumonitis: a case report. Medicine (Baltimore), 2018, 97(21): e10681.
3. Kawakami H, Miyabayashi T, Tsubata C, et al. Spontaneous resolution of thoracic radiation therapy-induced organizing pneumonia: a case series. Respir Med Case Rep, 2019, 26: 180-184.
4. Wolf MS, Chadha AD, Carroll CM, et al. Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury. Pediatr Radiol, 2015, 45(7): 1086-1090.
5. Conway JL, Long K, Ploquin N, et al. Unexpected symptomatic pneumonitis following breast tangent radiation: a case report. Cureus, 2015, 7(10): e363.
6. Hu Y, Li J, Su X. Fatal pneumonitis associated with postoperative intensity-modulated radiotherapy in lung cancer: case report and review. Oncol Lett, 2013, 5(2): 714-716.
7. Sakurai K, Kubo N, Shibutani M, et al. Five cases of severe radiation pneumonitis after chemoradiotherapy for esophageal cancer. Gan To Kagaku Ryoho, 2013, 40(12): 2139-2142.
8. Muraoka T, Bandoh S, Fujita J, et al. Corticosteroid refractory radiation pneumonitis that remarkably responded to cyclosporin A. Intern Med, 2002, 41(9): 730-703.
9. Bölke E, Matuschek C. Images in clinical medicine. Radiation pneumonitis after radiotherapy for breast cancer. N Engl J Med, 2009, 361(27): e65.
10. Miyagawa T, Mochizuki Y, Nakahara Y, et al. A case of severe radiation pneumonitis--a trial of plasma exchange. Nihon Kokyuki Gakkai Zasshi, 2009, 47(6): 481-485.
11. Huang Y, Zhang W, Yu F, et al. The cellular and molecular mechanism of radiation-induced lung injury. Med Sci Monit, 2017, 23: 3446-3450.
12. Torre-Bouscoulet L, Muñoz-Montaño WR, Martínez-Briseño D, et al. Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer. Respir Res, 2018, 19(1): 72.
13. Guilbault C, Garant A, Faria S, et al. Long-term outcomes of induction carboplatin and gemcitabine followed by concurrent radiotherapy with low-dose paclitaxel and gemcitabine for stage Ⅲ non-small-cell lung cancer. Clin Lung Cancer, 2017, 18: 565-571.
14. Chen Z, Wu Z, Ning W. Advances in molecular mechanisms and treatment of radiation-induced pulmonary fibrosis. Transl Oncol, 2019, 12(1): 162-169.
15. Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med, 2014, 370(22): 2071-2082.
16. Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med, 2019, 380(26): 2518-2528.
17. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med, 2019, 381(18): 1718-1727.
18. Capelletto E, Migliorino MR, Morabito A, et al. Final results of the SENECA (SEcond line NintEdanib in non-small cell lung CAncer) trial. Lung Cancer, 2019, 134: 210-217.
19. Forster M, Hackshaw A, De Pas T, et al. A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3). Lung Cancer, 2018, 120: 27-33.
20. Henkenberens C, Janssen S, Lavae-Mokhtari M, et al. Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade Ⅱ after radiotherapy - a single-centre experience. Radiat Oncol, 2016, 11: 12.
21. Hanania AN, Mainwaring W, Ghebre YT, et al. Radiation-induced lung injury: assessment and management. Chest, 2019, 156(1): 150-162.
22. Jackson IL, Vujaskovic Z, Down JD. A further comparison of pathologies after thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation-induced lung damage. Radiat Res, 2011, 175: 510-518.
23. Otani K, Nishiyama K, Ito Y, et al. Steroid treatment increases the recurrence of radiation-induced organizing pneumonia after breast-conserving therapy. Cancer Med, 2014, 3(4): 947-953.
24. Wollin L, Distler JHW, Redente EF, et al. Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases. Eur Respir J, 2019, 54(3): 1900161.
25. Jin H, Yoo Y, Kim Y, et al. Radiation-induced lung fibrosis: preclinical animal models and therapeutic strategies. Cancers (Basel), 2020, 12(6): 1561.
26. Westbury CB, Yarnold JR. Radiation fibrosis--current clinical and therapeutic perspectives. Clin Oncol (R Coll Radiol), 2012, 24(10): 657-672.
27. 刘文秀, 杨娟, 曹博, 等. 甲磺酸伊马替尼对放射性肺炎小鼠肺部氧化应激指标及转化生长因子-β1 表达影响的研究. 中国呼吸与危重监护杂志, 2017, 16(5): 446-450.
28. De Ruysscher D, Granton PV, Lieuwes NG, et al. Nintedanib reduces radiation-induced microscopic lung fibrosis but this cannot be monitored by CT imaging: a preclinical study with a high precision image-guided irradiator. Radiother Oncol, 2017, 124(3): 482-487.

Chinese Journal of Respiratory and Critical Care Medicine

尼达尼布治疗放射性肺损伤一例并文献复习

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