Risk factors for radiation-induced lung injury in patients with advanced non-small cell lung cancer: implication for treatment strategies

Sha Sha, Jigang Dong, Maoyu Wang, Ziyu Chen, Peng Gao, Sha Sha, Jigang Dong, Maoyu Wang, Ziyu Chen, Peng Gao

Abstract

Background: The radiation-induced lung injury (RILI) in patients with advanced non-small cell lung cancer (NSCLS) is very common in clinical settings; we aimed to evaluate the risk factors of RILI in NSCLS patients, to provide insights into the treatment of NSCLS.

Methods: NSCLC patients undergoing three-dimensional conformal radiotherapy (3D-CRT) in our hospital from June 1, 2018, to June 30, 2020, were included. The characteristics and treatments of RILI and non-RILI patients were analyzed. Logistic regression analyses were conducted to assess the risk factors of RILI in patients with NSCLC.

Results: A total of 126 NSCLC patients were included; the incidence of RILI in NSCLC patients was 35.71%. There were significant differences in diabetes, smoke, chronic obstructive pulmonary disease (COPD), concurrent chemotherapy, radiotherapy dose, and planning target volume (PTV) between the RILI group and the non-RILI group (all P < 0.05). Logistic regression analyses indicated that diabetes (OR 3.076, 95%CI 1.442~5.304), smoke (OR 2.745, 95%CI 1.288~4.613), COPD (OR 3.949, 95%CI 1.067~5.733), concurrent chemotherapy (OR 2.072, 95%CI 1.121~3.498), radiotherapy dose ≥ 60 Gy (OR 3.841, 95%CI 1.932~5.362), and PTV ≥ 396 (OR 1.247, 95%CI 1.107~1.746) were the independent risk factors of RILI in patients with NSCLC (all P < 0.05).

Conclusions: RILI is commonly seen in NSCLS patients; early targeted measures are warranted for patients with those risk factors; future studies with larger sample sizes and different areas are needed to further elucidate the influencing factors of RILI in the treatment of NSCLS.

Keywords: Care; Lung injury; Non-small cell lung cancer; Radiation; Treatment.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

References

    1. Ye Z, Huang Y, Ke J, Zhu X, Leng S, Luo H. Breakthrough in targeted therapy for non-small cell lung cancer. Biomed Pharmacother. 2021;133:111079. doi: 10.1016/j.biopha.2020.111079.
    1. Feng L, Wang Z, Jing L, Zhou Z, Shi S, Deng R, Liu Y, Meng Q. Recombinant human endostatin combined with chemotherapy for advanced squamous cell lung cancer: a meta-analysis. World J Surg Oncol. 2021;19(1):64. doi: 10.1186/s12957-021-02161-1.
    1. Bernchou U, Christiansen RL, Asmussen JT, Schytte T, Hansen O, Brink C. Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer. Radiother Oncol. 2017;123(1):93–98. doi: 10.1016/j.radonc.2017.02.001.
    1. Wei X, Jiang Y, Zhang X, Feng S, Zhou B, Ye X, Xing H, Xu Y, Shi J, Guo W, Zhou D, Zhang H, Sun H, Huang C, Lu C, Zheng Y, Meng Y, Huang B, Cong W, Lau WY, Cheng S. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol. 2019;37(24):2141–2151. doi: 10.1200/JCO.18.02184.
    1. Hirose TA, Arimura H, Ninomiya K, Yoshitake T, Fukunaga JI, Shioyama Y. Radiomic prediction of radiation pneumonitis on pretreatment planning computed tomography images prior to lung cancer stereotactic body radiation therapy. Sci Rep. 2020;10(1):20424. doi: 10.1038/s41598-020-77552-7.
    1. Farr KP, Khalil AA, Grau C. Patient-reported lung symptoms and quality of life before and after radiation therapy for non-small cell lung cancer: correlation with radiation pneumonitis and functional imaging. Acta Oncol. 2019;58(10):1523–1527. doi: 10.1080/0284186X.2019.1634835.
    1. Jirkovska M, Novak T, Malinova B, Lohynska R. Three-dimensional conformal radiotherapy versus intensity modulated radiotherapy with simultaneous integrated boost in the treatment of locally advanced head and neck carcinoma. Neoplasma. 2019;66(5):830–838. doi: 10.4149/neo_2018_181209N941.
    1. Sukari A, Nagasaka M, Alhasan R, Patel D, Wozniak A, Ramchandren R, Vaishampayan U, Weise A, Flaherty L, Jang H, et al. Cancer site and adverse events induced by immune checkpoint inhibitors: a retrospective analysis of real-life experience at a single institution. Anticancer Res. 2019;39(2):781–790. doi: 10.21873/anticanres.13175.
    1. Peng F, Stanton P, Bi N, Kong F. Dose-related changes for lung ventilation and perfusion and prediction for radiation-induced lung injury during the course of radiotherapy in patients with non-small cell lung cancer. Pract Radiat Oncol. 2013;3(2 Suppl 1):S26. doi: 10.1016/j.prro.2013.01.091.
    1. Wang D, Sun J, Zhu J, Li X, Zhen Y, Sui S. Functional dosimetric metrics for predicting radiation-induced lung injury in non-small cell lung cancer patients treated with chemoradiotherapy. Radiat Oncol. 2012;7(1):69. doi: 10.1186/1748-717X-7-69.
    1. Zhong L, Suo J, Wang Y, Han J, Zhou H, Wei H, Zhu J. Prognosis of limited-stage small cell lung cancer with comprehensive treatment including radical resection. World J Surg Oncol. 2020;18(1):27. doi: 10.1186/s12957-020-1807-1.
    1. Itamura H, Ohguri T, Yahara K, Nakahara S, Kakinouchi S, Morisaki T, Yatera K, Tanaka F, Korogi Y. Pembrolizumab-induced radiation recall pneumonitis after the resolution of typical asymptomatic radiation pneumonitis. J UOEH. 2020;42(3):261–266. doi: 10.7888/juoeh.42.261.
    1. Shi L, He Y, Yuan Z, Benedict S, Valicenti R, Qiu J, Rong Y. Radiomics for response and outcome assessment for non-small cell lung cancer. Technol Cancer Res Treat. 2018;17:1533033818782788. doi: 10.1177/1533033818782788.
    1. Palma G, Monti S, Thor M, Rimner A, Deasy JO, Cella L. Spatial signature of dose patterns associated with acute radiation-induced lung damage in lung cancer patients treated with stereotactic body radiation therapy. Phys Med Biol. 2019;64(15):155006. doi: 10.1088/1361-6560/ab2e16.
    1. Li YQ, Zheng Z, Liu QX, Lu X, Zhou D, Zhang J, Zheng H, Dai JG. Moesin as a prognostic indicator of lung adenocarcinoma improves prognosis by enhancing immune lymphocyte infiltration. World J Surg Oncol. 2021;19(1):109. doi: 10.1186/s12957-021-02229-y.
    1. Chang SC, Lai YC, Hung JC, Chang CY. Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer. Medicine (Baltimore) 2019;98(8):e14463. doi: 10.1097/MD.0000000000014463.
    1. Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94(8):1623–1640. doi: 10.1016/j.mayocp.2019.01.013.
    1. Reck M, Rabe KF. Precision diagnosis and treatment for advanced non-small-cell lung cancer. N Engl J Med. 2017;377(9):849–861. doi: 10.1056/NEJMra1703413.
    1. Jahangiri P, Pournazari K, Torigian DA, Werner TJ, Swisher-McClure S, Simone CB, 2nd, Alavi A. A prospective study of the feasibility of FDG-PET/CT imaging to quantify radiation-induced lung inflammation in locally advanced non-small cell lung cancer patients receiving proton or photon radiotherapy. Eur J Nucl Med Mol Imaging. 2019;46(1):206–216. doi: 10.1007/s00259-018-4154-5.
    1. Hanaoka J, Yoden M, Hayashi K, Shiratori T, Okamoto K, Kaku R, Kawaguchi Y, Ohshio Y, Sonoda A. Dynamic perfusion digital radiography for predicting pulmonary function after lung cancer resection. World J Surg Oncol. 2021;19(1):43. doi: 10.1186/s12957-021-02158-w.
    1. Li Q, Liu Y, Su B, Zhao H, Lin Q, Zhu Y, Zhang L, Weng D, Gong X, Sun X, Xu Y. The CT appearance pattern of radiation-induced lung injury and tumor recurrence after stereotactic body radiation therapy in early stage non-small cell lung cancer. Transl Lung Cancer Res. 2020;9(3):713–721. doi: 10.21037/tlcr-20-609.
    1. Mehta V. Open label multicenter trial of subcutaneous amifostine (Ethyol) in the prevention of radiation induced esophagitis and pneumonitis in patients with measurable, unresectable non-small cell lung cancer. Semin Oncol. 2004;31(6 Suppl 18):42–46. doi: 10.1053/j.seminoncol.2004.12.011.
    1. Chen J, Lu JJ, Ma N, Zhao J, Chen C, Fan M, Jiang G, Mao J. Early stage non-small cell lung cancer treated with pencil beam scanning particle therapy: retrospective analysis of early results on safety and efficacy. Radiat Oncol. 2019;14(1):16. doi: 10.1186/s13014-019-1216-1.
    1. Wu LL, Lai JJ, Liu X, Huang YY, Lin P, Long H, Zhang LJ, Ma GW. Association between number of dissected lymph nodes and survival in stage IA non-small cell lung cancer: a propensity score matching analysis. World J Surg Oncol. 2020;18(1):322. doi: 10.1186/s12957-020-02090-5.
    1. Zhang H, Jiang T, Yu H, Lu H, Zhao Y, Zhang Y, Fu J, Chen W, Dong P, Zang L, Song H. Polyene phosphatidylcholine protects against radiation induced tissue injury without affecting radiotherapeutic efficacy in lung cancer. Am J Cancer Res. 2019;9(6):1091–1103.
    1. Moran A, Daly ME, Yip SSF, Yamamoto T. Radiomics-based assessment of radiation-induced lung injury after stereotactic body radiotherapy. Clin Lung Cancer. 2017;18(6):e425–e431. doi: 10.1016/j.cllc.2017.05.014.
    1. Torre-Bouscoulet L, Munoz-Montano WR, Martinez-Briseno D, Lozano-Ruiz FJ, Fernandez-Plata R, Beck-Magana JA, Garcia-Sancho C, Guzman-Barragan A, Vergara E, Blake-Cerda M, 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. doi: 10.1186/s12931-018-0775-2.
    1. Itonaga T, Sugahara S, Mikami R, Saito T, Yamada T, Kurooka M, Shiraishi S, Okubo M, Saito K. Evaluation of the relationship between the range of radiation-induced lung injury on CT images after IMRT for stage I lung cancer and dosimetric parameters. Ann Med. 2021;53(1):267–273. doi: 10.1080/07853890.2020.1869297.
    1. Sheng Y, Chen K, Jiang W, Wu Z, Zhang W, Jing H, Wang L, Qu C, Ren H. PD-1 restrains IL-17A production from gammadelta T cells to modulate acute radiation-induced lung injury. Transl Lung Cancer Res. 2021;10(2):685–698. doi: 10.21037/tlcr-20-838.
    1. Menoux I, Antoni D, Mazzara C, Labani A, Charloux A, Quoix E, Falcoz PE, Truntzer P, Noel G. Radiation-induced lung toxicity predictors: retrospective analysis of 90 patients treated with stereotactic body radiation therapy for stage I non-small-cell lung carcinoma. Cancer Radiother. 2020;24(2):120–127. doi: 10.1016/j.canrad.2019.11.003.
    1. Yue J, Shi Q, Xu T, Jeter M, Chen TY, Komaki R, Gomez DR, Pan T, Cleeland CS, Liao Z, Wang XS. Patient-reported lung symptoms as an early signal of impending radiation pneumonitis in patients with non-small cell lung cancer treated with chemoradiation: an observational study. Qual Life Res. 2018;27(6):1563–1570. doi: 10.1007/s11136-018-1834-3.
    1. Wang W, Men Y, Wang J, Zhou Z, Chen D, Xiao Z, Feng Q, Lv J, Liang J, Bi N, Gao S, Wang L, Hui Z. Postoperative radiotherapy is effective in improving survival of patients with stage pIII-N2 non-small-cell lung cancer after pneumonectomy. BMC Cancer. 2019;19(1):478. doi: 10.1186/s12885-019-5692-3.
    1. Zhou Y, Yan T, Zhou X, Cao P, Luo C, Zhou L, Xu Y, Liu Y, Xue J, Wang J, Wang Y, Lu Y, Liang B, Gong Y. Acute severe radiation pneumonitis among non-small cell lung cancer (NSCLC) patients with moderate pulmonary dysfunction receiving definitive concurrent chemoradiotherapy: impact of pre-treatment pulmonary function parameters. Strahlenther Onkol. 2020;196(6):505–514. doi: 10.1007/s00066-019-01552-4.
    1. Xiao L, Yang G, Chen J, Yang Y, Meng X, Wang X, Wu Q, Huo Z, Yu Q, Yu J, Kong FM(S), Yuan S. Comparison of predictive powers of functional and anatomic dosimetric parameters for radiation-induced lung toxicity in locally advanced non-small cell lung cancer. Radiother Oncol. 2018;129(2):242–248. doi: 10.1016/j.radonc.2018.09.005.
    1. Nakajima M, Yamamoto N, Hayashi K, Karube M, Ebner DK, Takahashi W, Anzai M, Tsushima K, Tada Y, Tatsumi K, Miyamoto T, Tsuji H, Fujisawa T, Kamada T. Carbon-ion radiotherapy for non-small cell lung cancer with interstitial lung disease: a retrospective analysis. Radiat Oncol. 2017;12(1):144. doi: 10.1186/s13014-017-0881-1.
    1. Menoux I, Le Fevre C, Noel G, Antoni D. Radiation-induced lung toxicity predictors after stereotactic radiation therapy for non-small cell lung carcinoma stage I. Cancer Radiother. 2018;22(8):826–838. doi: 10.1016/j.canrad.2017.12.007.
    1. Ireland RH, Din OS, Swinscoe JA, Woodhouse N, van Beek EJ, Wild JM, Hatton MQ. Detection of radiation-induced lung injury in non-small cell lung cancer patients using hyperpolarized helium-3 magnetic resonance imaging. Radiother Oncol. 2010;97(2):244–248. doi: 10.1016/j.radonc.2010.07.013.
    1. Kalman NS, Hugo GD, Mahon RN, Deng X, Mukhopadhyay ND, Weiss E. Diabetes mellitus and radiation induced lung injury after thoracic stereotactic body radiotherapy. Radiother Oncol. 2018;129(2):270–276. doi: 10.1016/j.radonc.2018.08.024.
    1. Liu Y, Zhu Y, Wu R, Hu M, Zhang L, Lin Q, Weng D, Sun X, Liu Y, Xu Y. Stereotactic body radiotherapy for early stage non-small cell lung cancer in patients with subclinical interstitial lung disease. Transl Lung Cancer Res. 2020;9(6):2328–2336. doi: 10.21037/tlcr-20-1050.
    1. Nobashi TW, Nishimoto Y, Kawata Y, Yutani H, Nakamura M, Tsuji Y, Yoshida A, Sugimoto A, Yamamoto T, Alam IS, Noma S. Clinical and radiological features of immune checkpoint inhibitor-related pneumonitis in lung cancer and non-lung cancers. Br J Radiol. 2020;93(1115):20200409. doi: 10.1259/bjr.20200409.
    1. Bousabarah K, Temming S, Hoevels M, Borggrefe J, Baus WW, Ruess D, Visser-Vandewalle V, Ruge M, Kocher M, Treuer H. Radiomic analysis of planning computed tomograms for predicting radiation-induced lung injury and outcome in lung cancer patients treated with robotic stereotactic body radiation therapy. Strahlenther Onkol. 2019;195(9):830–842. doi: 10.1007/s00066-019-01452-7.
    1. Evison M, Barrett E, Cheng A, Mulla A, Walls G, Johnston D, McAleese J, Moore K, Hicks J, Blyth K, Denholm M, Magee L, Gilligan D, Silverman S, Hiley C, Qureshi M, Clinch H, Hatton M, Philipps L, Brown S, O'Brien M, McDonald F, Faivre-Finn C. Predicting the risk of disease recurrence and death following curative-intent radiotherapy for non-small cell lung cancer: the development and validation of two scoring systems from a large multicentre UK cohort. Clin Oncol (R Coll Radiol) 2021;33(3):145–154. doi: 10.1016/j.clon.2020.09.001.
    1. Shintani T, Kishi N, Matsuo Y, Ogura M, Mitsuyoshi T, Araki N, et al. Incidence and risk factors of symptomatic radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent chemoradiotherapy and consolidation durvalumab. Clin Lung Cancer. 2021. 10.1016/j.cllc.2021.01.017.

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