Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Related articles

Radiation-induced lung injury

INTRODUCTION

Radiation-induced lung injury was first described in 1898, soon after the development of roentgenograms [1]. The distinction between two separate types of radiation-induced lung injury, radiation pneumonitis and radiation fibrosis, was made in 1925 [2]. Both types of lung injury are observed today in patients who have undergone thoracic irradiation for the treatment of lung, breast, or hematologic malignancies. Radiation-induced damage to normal lung parenchyma remains the dose-limiting factor in chest radiotherapy, and can involve other structures within the thorax in addition to the lungs (table 1).

A large body of literature describes the histopathologic, biochemical, kinetic, physiologic, and molecular responses of lung cells to ionizing radiation [3-7]. However, the clinical diagnosis of radiation-induced lung injury is often complicated by the presence of other conditions, including malignancy, infection, and cardiogenic pulmonary edema [8]. Radiation-induced lung injury will be reviewed here. The cardiac effects of therapeutic radiation are discussed separately. (See "Cardiotoxicity of radiation therapy for malignancy".)

PATHOGENESIS

Ionizing radiation causes the localized release of sufficient energy to break strong chemical bonds and generate highly reactive free radical species. Cellular molecules including peptides, lipids, and DNA can be affected directly or indirectly via the interaction of the ionizing radiation with tissue water.

Overexpression of a transgene for manganese superoxide dismutase protects against the late fibrotic response in a murine model of radiation pneumonitis, and confirms the role of oxygen radicals in the pathogenesis of radiation-induced fibrosis [9]. There have been preclinical studies of gene therapy combined with chest irradiation to increase tissue expression of manganese superoxide dismutase and limit radiation-induced pulmonary damage [10].

Radiation-induced lung injury results from the combination of direct cytotoxicity upon normal lung tissue and, perhaps more importantly, the development of fibrosis triggered by radiation-induced cellular signal transduction. The cytotoxic effect is largely a consequence of DNA damage that causes clonogenic death in normal lung epithelial cells, though apoptotic pathways are also induced by radiation. The development of fibrosis that can compromise lung function is mediated by a number of different cytokines, as discussed below.

                                  

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2014. | This topic last updated: Jun 10, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Bergonie, J, Teissier, J. Rapport sur l'action des rayons X sur la tuberculose. Arch Electr Med 1898; 6:334.
  2. Evans, WA, Leucutia, T. Intrathoracic changes induced by heavy irradiation. AJR 1925; 13:203.
  3. Abratt RP, Morgan GW. Lung toxicity following chest irradiation in patients with lung cancer. Lung Cancer 2002; 35:103.
  4. Coggle JE, Lambert BE, Moores SR. Radiation effects in the lung. Environ Health Perspect 1986; 70:261.
  5. McDonald S, Rubin P, Phillips TL, Marks LB. Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int J Radiat Oncol Biol Phys 1995; 31:1187.
  6. Molls M, Herrmann Th, Steinberg F, Feldmann HJ. Radiopathology of the lung: experimental and clinical observations. Recent Results Cancer Res 1993; 130:109.
  7. Movsas B, Raffin TA, Epstein AH, Link CJ Jr. Pulmonary radiation injury. Chest 1997; 111:1061.
  8. Kocak Z, Evans ES, Zhou SM, et al. Challenges in defining radiation pneumonitis in patients with lung cancer. Int J Radiat Oncol Biol Phys 2005; 62:635.
  9. Epperly M, Bray J, Kraeger S, et al. Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther 1998; 5:196.
  10. Greenberger JS, Epperly MW, Gretton J, et al. Radioprotective gene therapy. Curr Gene Ther 2003; 3:183.
  11. Haston CK, Begin M, Dorion G, Cory SM. Distinct loci influence radiation-induced alveolitis from fibrosing alveolitis in the mouse. Cancer Res 2007; 67:10796.
  12. Kelsey CR, Rosenstein BS, Marks LB. Predicting toxicity from radiation therapy--it's genetic, right? Cancer 2012; 118:3450.
  13. Wen J, Liu H, Wang Q, et al. Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy. Eur J Cancer 2014; 50:1706.
  14. Kuptsova N, Chang-Claude J, Kropp S, et al. Genetic predictors of long-term toxicities after radiation therapy for breast cancer. Int J Cancer 2008; 122:1333.
  15. Suga T, Ishikawa A, Kohda M, et al. Haplotype-based analysis of genes associated with risk of adverse skin reactions after radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 2007; 69:685.
  16. Giotopoulos G, Symonds RP, Foweraker K, et al. The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causes. Br J Cancer 2007; 96:1001.
  17. Mak RH, Alexander BM, Asomaning K, et al. A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy. Cancer 2012; 118:3654.
  18. Zhang L, Yang M, Bi N, et al. ATM polymorphisms are associated with risk of radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys 2010; 77:1360.
  19. Xiong H, Liao Z, Liu Z, et al. ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy. Int J Radiat Oncol Biol Phys 2013; 85:1066.
  20. Anscher MS, Kong FM, Andrews K, et al. Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 1998; 41:1029.
  21. Anscher MS, Marks LB, Shafman TD, et al. Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy. Int J Radiat Oncol Biol Phys 2003; 56:988.
  22. Mazeron R, Etienne-Mastroianni B, Pérol D, et al. Predictive factors of late radiation fibrosis: a prospective study in non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2010; 77:38.
  23. Chen Y, Williams J, Ding I, et al. Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol 2002; 12:26.
  24. Chen Y, Rubin P, Williams J, et al. Circulating IL-6 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 2001; 49:641.
  25. Rubin P, Johnston CJ, Williams JP, et al. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 1995; 33:99.
  26. Fuks Z, Persaud RS, Alfieri A, et al. Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Res 1994; 54:2582.
  27. Rosiello RA, Merrill WW, Rockwell S, et al. Radiation pneumonitis. Bronchoalveolar lavage assessment and modulation by a recombinant cytokine. Am Rev Respir Dis 1993; 148:1671.
  28. Adawi A, Zhang Y, Baggs R, et al. Blockade of CD40-CD40 ligand interactions protects against radiation-induced pulmonary inflammation and fibrosis. Clin Immunol Immunopathol 1998; 89:222.
  29. Martín C, Romero S, Sánchez-Payá J, et al. Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation. Eur Respir J 1999; 13:727.
  30. Bradley JD, Hope A, El Naqa I, et al. A nomogram to predict radiation pneumonitis, derived from a combined analysis of RTOG 9311 and institutional data. Int J Radiat Oncol Biol Phys 2007; 69:985.
  31. Pang Q, Wei Q, Xu T, et al. Functional promoter variant rs2868371 of HSPB1 is associated with risk of radiation pneumonitis after chemoradiation for non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2013; 85:1332.
  32. Morgan GW, Breit SN. Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys 1995; 31:361.
  33. Respiratory system. In: Clinical Radiation Pathology, Rubin P, Casseratt GW (Eds), WB Saunders, Philadelphia 1968. p.423.
  34. Marks LB, Bentzen SM, Deasy JO, et al. Radiation dose-volume effects in the lung. Int J Radiat Oncol Biol Phys 2010; 76:S70.
  35. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010; 76:S10.
  36. Lind PA, Marks LB, Hardenbergh PH, et al. Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys 2002; 52:137.
  37. Lingos TI, Recht A, Vicini F, et al. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 1991; 21:355.
  38. Kimsey FC, Mendenhall NP, Ewald LM, et al. Is radiation treatment volume a predictor for acute or late effect on pulmonary function? A prospective study of patients treated with breast-conserving surgery and postoperative irradiation. Cancer 1994; 73:2549.
  39. Kim TH, Cho KH, Pyo HR, et al. Dose-volumetric parameters for predicting severe radiation pneumonitis after three-dimensional conformal radiation therapy for lung cancer. Radiology 2005; 235:208.
  40. Carruthers SA, Wallington MM. Total body irradiation and pneumonitis risk: a review of outcomes. Br J Cancer 2004; 90:2080.
  41. Kwa SL, Lebesque JV, Theuws JC, et al. Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys 1998; 42:1.
  42. Fay M, Tan A, Fisher R, et al. Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 2005; 61:1355.
  43. Graham MV, Purdy JA, Emami B, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1999; 45:323.
  44. Roach M 3rd, Gandara DR, Yuo HS, et al. Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors. J Clin Oncol 1995; 13:2606.
  45. Kobayashi H, Uno T, Isobe K, et al. Radiation pneumonitis following twice-daily radiotherapy with concurrent carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer. Jpn J Clin Oncol 2010; 40:464.
  46. Rancati T, Ceresoli GL, Gagliardi G, et al. Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study. Radiother Oncol 2003; 67:275.
  47. Taghian AG, Assaad SI, Niemierko A, et al. Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 2001; 93:1806.
  48. Urbanic JJ, Lally B, Blackstock AW. "The best-laid plans ... often go awry ...". J Thorac Oncol 2009; 4:783.
  49. Lind JS, Senan S, Smit EF. Pulmonary toxicity after bevacizumab and concurrent thoracic radiotherapy observed in a phase I study for inoperable stage III non-small-cell lung cancer. J Clin Oncol 2012; 30:e104.
  50. Rengan R, Mick R, Pryma D, et al. A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small cell lung cancer: a report of toxicities and clinical response. J Thorac Oncol 2012; 7:709.
  51. Chakravarthy A, Johnson D, Choy H. The role of radiation, with or without chemotherapy, in the management of NSCLC. Oncology (Williston Park) 1999; 13:93.
  52. Arrieta O, Gallardo-Rincón D, Villarreal-Garza C, et al. High frequency of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin. J Thorac Oncol 2009; 4:845.
  53. Zinner RG, Komaki R, Cox JD, et al. Dose escalation of gemcitabine is possible with concurrent chest three-dimensional rather than two-dimensional radiotherapy: a phase I trial in patients with stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2009; 73:119.
  54. Wang S, Liao Z, Wei X, et al. Association between systemic chemotherapy before chemoradiation and increased risk of treatment-related pneumonitis in esophageal cancer patients treated with definitive chemoradiotherapy. J Thorac Oncol 2008; 3:277.
  55. Choy H, Jain AK, Moughan J, et al. RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by adjuvant chemotherapy for patients with favorable prognosis inoperable stage IIIA/B non-small cell lung cancer. J Thorac Oncol 2009; 4:80.
  56. Socinski MA, Blackstock AW, Bogart JA, et al. Randomized phase II trial of induction chemotherapy followed by concurrent chemotherapy and dose-escalated thoracic conformal radiotherapy (74 Gy) in stage III non-small-cell lung cancer: CALGB 30105. J Clin Oncol 2008; 26:2457.
  57. Mao J, Kocak Z, Zhou S, et al. The impact of induction chemotherapy and the associated tumor response on subsequent radiation-related changes in lung function and tumor response. Int J Radiat Oncol Biol Phys 2007; 67:1360.
  58. Robnett TJ, Machtay M, Vines EF, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys 2000; 48:89.
  59. Monson JM, Stark P, Reilly JJ, et al. Clinical radiation pneumonitis and radiographic changes after thoracic radiation therapy for lung carcinoma. Cancer 1998; 82:842.
  60. Venkatramani R, Kamath S, Wong K, et al. Correlation of clinical and dosimetric factors with adverse pulmonary outcomes in children after lung irradiation. Int J Radiat Oncol Biol Phys 2013; 86:942.
  61. Johansson S, Bjermer L, Franzen L, Henriksson R. Effects of ongoing smoking on the development of radiation-induced pneumonitis in breast cancer and oesophagus cancer patients. Radiother Oncol 1998; 49:41.
  62. Takeda A, Kunieda E, Ohashi T, et al. Severe COPD is correlated with mild radiation pneumonitis following stereotactic body radiotherapy. Chest 2012; 141:858.
  63. Yirmibesoglu E, Higginson DS, Fayda M, et al. Challenges scoring radiation pneumonitis in patients irradiated for lung cancer. Lung Cancer 2012; 76:350.
  64. Varga Z, Cserháti A, Kelemen G, et al. Role of systemic therapy in the development of lung sequelae after conformal radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 2011; 80:1109.
  65. Katayama N, Sato S, Katsui K, et al. Analysis of factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy. Int J Radiat Oncol Biol Phys 2009; 73:1049.
  66. Hochstrasser A, Benz G, Joerger M, et al. Interstitial pneumonitis after treatment with pemetrexed: a rare event? Chemotherapy 2012; 58:84.
  67. Bischof M, Weber KJ, Blatter J, et al. Interaction of pemetrexed disodium (ALIMTA, multitargeted antifolate) and irradiation in vitro. Int J Radiat Oncol Biol Phys 2002; 52:1381.
  68. Allen AM, Czerminska M, Jänne PA, et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys 2006; 65:640.
  69. Moreno M, Aristu J, Ramos LI, et al. Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer. Clin Transl Oncol 2007; 9:596.
  70. Chen S, Zhou S, Zhang J, et al. A neural network model to predict lung radiation-induced pneumonitis. Med Phys 2007; 34:3420.
  71. Zhao L, Sheldon K, Chen M, et al. The predictive role of plasma TGF-beta1 during radiation therapy for radiation-induced lung toxicity deserves further study in patients with non-small cell lung cancer. Lung Cancer 2008; 59:232.
  72. Yuan X, Liao Z, Liu Z, et al. Single nucleotide polymorphism at rs1982073:T869C of the TGFbeta 1 gene is associated with the risk of radiation pneumonitis in patients with non-small-cell lung cancer treated with definitive radiotherapy. J Clin Oncol 2009; 27:3370.
  73. Ma LD, Taylor GA, Wharam MD, Wiley JM. "Recall" pneumonitis: adriamycin potentiation of radiation pneumonitis in two children. Radiology 1993; 187:465.
  74. Schweitzer VG, Juillard GJ, Bajada CL, Parker RG. Radiation recall dermatitis and pneumonitis in a patient treated with paclitaxel. Cancer 1995; 76:1069.
  75. Schwarte S, Wagner K, Karstens JH, Bremer M. Radiation recall pneumonitis induced by gemcitabine. Strahlenther Onkol 2007; 183:215.
  76. Jeter MD, Jänne PA, Brooks S, et al. Gemcitabine-induced radiation recall. Int J Radiat Oncol Biol Phys 2002; 53:394.
  77. Kataoka M, Kawamura M, Nishiyama Y, et al. [A case with delayed-onset radiation pneumonitis suspected to be induced by oral etoposide]. Nihon Igaku Hoshasen Gakkai Zasshi 1992; 52:641.
  78. Epperly MW, Guo H, Gretton JE, Greenberger JS. Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. Am J Respir Cell Mol Biol 2003; 29:213.
  79. Theise ND, Henegariu O, Grove J, et al. Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow. Exp Hematol 2002; 30:1333.
  80. Arbetter KR, Prakash UB, Tazelaar HD, Douglas WW. Radiation-induced pneumonitis in the "nonirradiated" lung. Mayo Clin Proc 1999; 74:27.
  81. Kwok E, Chan CK. Corticosteroids and azathioprine do not prevent radiation-induced lung injury. Can Respir J 1998; 5:211.
  82. Takigawa N, Segawa Y, Saeki T, et al. Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity. Int J Radiat Oncol Biol Phys 2000; 48:751.
  83. Gustafson G, Vicini F, Freedman L, et al. High dose rate endobronchial brachytherapy in the management of primary and recurrent bronchogenic malignancies. Cancer 1995; 75:2345.
  84. Leung TW, Lau WY, Ho SK, et al. Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys 1995; 33:919.
  85. Gross NJ. Pulmonary effects of radiation therapy. Ann Intern Med 1977; 86:81.
  86. Abratt RP, Morgan GW, Silvestri G, Willcox P. Pulmonary complications of radiation therapy. Clin Chest Med 2004; 25:167.
  87. Yamashita H, Kobayashi-Shibata S, Terahara A, et al. Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy. Radiat Oncol 2010; 5:32.
  88. Ikezoe J, Takashima S, Morimoto S, et al. CT appearance of acute radiation-induced injury in the lung. AJR Am J Roentgenol 1988; 150:765.
  89. Park KJ, Chung JY, Chun MS, Suh JH. Radiation-induced lung disease and the impact of radiation methods on imaging features. Radiographics 2000; 20:83.
  90. Choi YW, Munden RF, Erasmus JJ, et al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics 2004; 24:985.
  91. Palma DA, Senan S, Haasbeek CJ, et al. Radiological and clinical pneumonitis after stereotactic lung radiotherapy: a matched analysis of three-dimensional conformal and volumetric-modulated arc therapy techniques. Int J Radiat Oncol Biol Phys 2011; 80:506.
  92. Robbins ME, Brunso-Bechtold JK, Peiffer AM, et al. Imaging radiation-induced normal tissue injury. Radiat Res 2012; 177:449.
  93. Cudkowicz L, Cunningham M, Haldane EV. Effects of mediastinal irradiation upon respiratory function following mastectomy for carcinoma of breast. A five-year follow-up study. Thorax 1969; 24:359.
  94. Wohl ME, Griscom NT, Traggis DG, Jaffe N. Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function. Pediatrics 1975; 55:507.
  95. Lopez Guerra JL, Gomez D, Zhuang Y, et al. Change in diffusing capacity after radiation as an objective measure for grading radiation pneumonitis in patients treated for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2012; 83:1573.
  96. Lind PA, Marks LB, Jamieson TA, et al. Predictors for pneumonitis during locoregional radiotherapy in high-risk patients with breast carcinoma treated with high-dose chemotherapy and stem-cell rescue. Cancer 2002; 94:2821.
  97. Nakayama Y, Makino S, Fukuda Y, et al. Activation of lavage lymphocytes in lung injuries caused by radiotherapy for lung cancer. Int J Radiat Oncol Biol Phys 1996; 34:459.
  98. Pickrell JA, Abdel-Mageed AB. Radiation-induced pulmonary fibrosis. In: Lung Biology in Health and Disease: Pulmonary Fibrosis, Marcel Dekker, Inc, New York 1995. p.363.
  99. Gross NJ, Narine KR, Wade R. Protective effect of corticosteroids on radiation pneumonitis in mice. Radiat Res 1988; 113:112.
  100. Ozturk B, Egehan I, Atavci S, Kitapci M. Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial. Int J Radiat Oncol Biol Phys 2004; 58:213.
  101. McCarty MJ, Lillis P, Vukelja SJ. Azathioprine as a steroid-sparing agent in radiation pneumonitis. Chest 1996; 109:1397.
  102. Muraoka T, Bandoh S, Fujita J, et al. Corticosteroid refractory radiation pneumonitis that remarkably responded to cyclosporin A. Intern Med 2002; 41:730.
  103. Antonadou D, Coliarakis N, Synodinou M, et al. Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer. Int J Radiat Oncol Biol Phys 2001; 51:915.
  104. Vujaskovic Z, Feng QF, Rabbani ZN, et al. Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity. Exp Lung Res 2002; 28:577.
  105. Antonadou D. Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer. Semin Radiat Oncol 2002; 12:50.
  106. Gopal R. Pulmonary toxicity associated with the treatment of non-small cell lung cancer and the effects of cytoprotective strategies. Semin Oncol 2005; 32:S55.
  107. Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 2009; 27:127.
  108. Movsas B, Scott C, Langer C, et al. Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01. J Clin Oncol 2005; 23:2145.
  109. Ward WF, Molteni A, Ts'ao CH. Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817. Radiat Res 1989; 117:342.
  110. Kharofa J, Cohen EP, Tomic R, et al. Decreased risk of radiation pneumonitis with incidental concurrent use of angiotensin-converting enzyme inhibitors and thoracic radiation therapy. Int J Radiat Oncol Biol Phys 2012; 84:238.
  111. Borst GR, De Jaeger K, Belderbos JS, et al. Pulmonary function changes after radiotherapy in non-small-cell lung cancer patients with long-term disease-free survival. Int J Radiat Oncol Biol Phys 2005; 62:639.
  112. Theuws JC, Seppenwoolde Y, Kwa SL, et al. Changes in local pulmonary injury up to 48 months after irradiation for lymphoma and breast cancer. Int J Radiat Oncol Biol Phys 2000; 47:1201.