Radiation Induced Lung Injury: Prediction, Assessment and Management

  • Giridhar, Prashanth (Department of Radiotherapy, AIIMS) ;
  • Mallick, Supriya (Department of Radiotherapy, AIIMS) ;
  • Rath, Goura Kishore (Department of Radiotherapy, AIIMS) ;
  • Julka, Pramod Kumar (Department of Radiotherapy, AIIMS)
  • Published : 2015.04.14


Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.


Lung cancer;pneumonitis;radiation;fibrosis


  1. Medhora M, Gao F, Jacobs ER, Moulder JE (2012). Radiation damage to the lung: mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology, 17, 66-71.
  2. Molteni A, Moulder JE, Cohen EF, et al (2000). Control of radiation-induced pneumopathy and lung fibrosis by angiotensin-converting enzyme inhibitors and an angiotensin II type 1 receptor blocker. Int J Radiat Biol, 76, 523-32.
  3. Osterreicher J, Mokry J, Navratil L, et al (2001). The alveolar septal thickness and type II pneumocytes number in irradiated lungs, time expression and the effect of pentoxifylline. Acta Medica, 44, 15-9.
  4. Palma DA, Senan S, Tsujino K, et al (2013). Predicting radiation pneumonitis after chemoradiotherapy of lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys, 85, 444-50.
  5. Rancati T, Ceresoli GL, Gagliardi G, et al (2003). Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study. Radiother Oncol, 67, 275.
  6. Rube CE, Wilfert F, Palm J, et al (2004). Irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung. StrahlentherOnkol, 180, 442-8.
  7. Taghian AG, Assaad SI, Niemierko A, et al (2001). Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst, 93, 1806.
  8. Gao F, Fish BL, Moulder JE, et al (2013). Enalapril mitigates radiation-induced pneumonitis and pulmonary fibrosis if started 35 days after whole-thorax irradiation. Radiat Res, 180, 546-52.
  9. Ghafoori P, Marks LB, Vujaskovic Z, Kelsey CR (2008). Radiation-induced lung injury. Assessment Manage Prev Oncol, 22, 37-47.
  10. 1Hideomi Yamashita, Wataru Takahashi; Akihiro Haga; Keichi Nakagawa (2014). Radiation pneumonitis after SBRT for lung cancers. W J radiology, 6, 708-15.
  11. Hoover DA, Reid RH, Wong E, et al (2014). SPECT-based functional lung imaging for the prediction of radiation pneumonitis: a clinical and dosimetric correlation. J Med Imaging Radiat Oncol, 58, 214-22.
  12. Ivan R Vogelius, Soren M Bentzen (2012). A literature based Meta analyses of clinical risk factors for development of radiation induced pneumonitis. Acta Oncol, 51, 975-83.
  13. Juweid ME, Stroobants S, Hoekstra OS, et al (2007). Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging subcommittee of international harmonization project in lymphoma. J Clin Oncol, 25, 571-8.
  14. Kouloulias V, Zygogianni A, Efstathopoulos E, et al (2013). Suggestion for a new grading scale for radiation pneumonitis based on radiological findings of computerized tomography: Correlation with clinical and radiotherapeutic parameters in lung cancer patients. Asian Pac J Cancer Prev, 14, 2717-22.
  15. Lind JS, Senan S, Smit EF (2012). 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, 30, 104-8.
  16. McDonald S, Rubin P, Phillips TL, et al (1995). Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int J Radiat Oncol Biol Phys, 31, 1187.
  17. Zhao L, Sheldon K, Chen M, Yin MS (2008) predictive role of plasma TGF B1 during radiation therapy for radiation lung toxicity deserves further study in patients with NSCLC. Lung Cancer, 59, 232-9.
  18. Albert RK, Connett J, Bailey WC, et al (2011). Azithromycin for prevention of exacerbations of COPD. N Engl J Med, 365, 689-98.
  19. Anscher MS, Kong FM, Andrews K, et al (1998). Plasma TGF B1 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys, 41, 1029-35.
  20. Bradley J, Movsas B (2006). Radiation pneumonitis and esophagitis in thoracic irradiation. In: Small W, Woloschak GE, eds. Radiation Toxicity: a Practical Guide. New York, NY: Springer Science+Media Business, Inc, 43-52.
  21. Castillo R, Pham N, Ansari S, et al (2014). Pre-radiotherapy FDG PET predicts radiation pneumonitis in lung cancer. Radiat Oncol, 9, 74.
  22. Chen Y, Ollivier H, Williams J, et al (2005). IL 1a and IL 6 application to the predictive diagnosis of radiation pneumonitis. Int J Radiat Oncol Biol Phys, 62, 260-6.
  23. Cox JD, Stetz J, Pajak TF (1995). Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys, 31, 1341-6.
  24. Faria S, Lisbona R, Stem J, et al (2007). Is post-treatment FDG-PET/CT useful in differentiating tumor from fibrosis after curative radiation therapy (RT) alone for lung cancer? Int J Radiat Oncol Biol Phys, 69, 519-20.
  25. Fleckenstein K, Zgonjanin L, Chen L (2007). Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys, 68, 196-204.
  26. Tsujino K, Hirota S, Endo M, et al (2003). Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys, 55, 110-5.
  27. Tsujisaki M, Imai K, Irata H, et al (1991). Detection of circulating ICAM1 in malignant diseases. Clin Exp Immunology, 81, 3-8.
  28. Urbanic JJ, Lally B, Blackstock AW (2009). The best-laid plans ...often go awry...". J Thorac Oncol, 4, 783.
  29. Vujaskovic Z, Anscher MS, Feng QF. et al (2001). Radiation-induced hypoxia may peRILIetuate late normal tissue injury. Int J RadiatOncolBiolPhys, 50, 851-5.
  30. Wang J, Cao J, Yuan S, Ji W (2013). Poor baseline pulmonary function may not increase the risk of radiation induced lung toxicity. Int J Radiat Oncol Biol Phys, 85, 798-804.
  31. Xiong H, Liao Z, Liu Z, et al (2013). ATM polymorphisms predict severe radiation pneumonitis in ptients with nonsmall cell carcinoma lung treated with definitive radiation therapy. Int J Radiat Oncol Biol Phys, 85, 1066-73.
  32. Zhao W, Robbins ME (2009). Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: Therapeutic implications. Curr Med Chem, 16, 130-43.
  33. Thind K, Chen A, Friesen-Waldner L, et al (2012). Detection of radiation-induced lung injury using hyperpolarized (13) C magnetic resonance spectroscopy and imaging. Magn Reson Med, 70, 601-9.
  34. Trott KR, Herrmann T, Kasper M, et al (2004). Target cells in radiation pneumopathy. Int J Radiat Oncol Biol Phys, 58, 463-469.

Cited by

  1. Pilot Feasibility Study of Comprehensive Pulmonary Evaluation Following Lung Radiation Therapy vol.37, pp.7, 2015,
  2. Clinical development of new drug–radiotherapy combinations vol.13, pp.10, 2016,
  3. Addressing the Symptoms or Fixing the Problem? Developing Countermeasures against Normal Tissue Radiation Injury vol.186, pp.1, 2016,
  4. The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung vol.7, pp.1664-3224, 2016,
  5. The angiotensin-converting enzyme inhibitor captopril rescues mice from endotoxin-induced lethal hepatitis vol.23, pp.2, 2017,
  6. Manganese Superoxide Dismutase Gene–Modified Mesenchymal Stem Cells Attenuate Acute Radiation-Induced Lung Injury vol.28, pp.6, 2017,
  7. polysaccharide/chitosan microspheres for oligomeric proanthocyanidins vol.35, pp.13, 2017,
  8. Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects vol.8, pp.1664-3224, 2017,
  9. Effects of traditional oriental medicines as anti-cytotoxic agents in radiotherapy vol.13, pp.6, 2017,
  10. Antifibrotic Agent Pirfenidone Protects against Development of Radiation-Induced Pulmonary Fibrosis in a Murine Model vol.190, pp.4, 2018,
  11. Diagnosis of Idiopathic Pulmonary Fibrosis: Differential Diagnosis vol.6, pp.3, 2018,
  12. Efficacy and mechanisms underlying the effects of allogeneic umbilical cord mesenchymal stem cell transplantation on acute radiation injury in tree shrews pp.1573-0778, 2018,