Drug-Induced Interstitial Lung Disease in Oncology Patients

  • Rianne Wittenberg
  • Santiago Rossi
  • Cornelia Schaefer-Prokop
Part of the Medical Radiology book series (MEDRAD)


There are an ever-increasing number of drugs that can cause lung disease (Foucher and Camus 2008, Pneumotox online: the drug-induced lung diseases. See: www.pneumotox.com). Prognosis is variable from self-limiting to fast progression with potential lethal outcome. Especially for the latter, timely diagnosis and appropriate management are important. The role of imaging is eminent, given the aspecific character of clinical symptoms, the broad range of potential underlying reasons, and the potentially serious outcome. There is a broad overlap between computed tomography (CT) patterns known from interstitial lung diseases and the findings seen in drug-induced lung disease. We provide a general overview about CT patterns to be encountered in patients with drug-induced lung disease, followed by descriptions of findings related to specific drugs. A special focus lies on new molecular-targeted drugs. Aspects to consider for differential diagnosis are provided at the end of the chapter.


Lung Injury Interstitial Lung Disease Hypersensitivity Pneumonitis Usual Interstitial Pneumonia Diffuse Alveolar Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Adverse drug reactions


Acute interstitial pneumonia


Acute respiratory distress syndrome


Bronchoscopy with bronchoalveolar lavage


Computed tomography


Diffuse alveolar damage


Desquamative interstitial pneumonia


Epidermal growth factor receptor


Eosinophilic pneumonia


Hypersensitivity pneumonitis


Interstitial lung diseases


Lymphocytic interstitial pneumonia


Nonspecific interstitial pneumonia


Organizing pneumonia


Pneumocystis jirovecii pneumonia


Rheumatoid arthritis


Tumor necrosis factor


Usual interstitial pneumonia


  1. Abramson RG, Abramson VH, Chan E et al (2013) Complixations of targeted drug therapies for solid malignancies: manifestations and mechanisms. AJR 200(3):475–483PubMedCentralCrossRefPubMedGoogle Scholar
  2. Akoun GM, Cadranel JL, Rosenow EC et al (1991) Bronchoalveolar lavage cell data in drug induced pneumonitis. Allerg Immunol Paris 23(6):245–252PubMedGoogle Scholar
  3. Araujo MS, Fernandes FL, Kay FU et al (2013) Pneumomediastinum, subcutaneous emphysema, and pneumothorax after a pulmonary function testing in a patient with bleomycin-induced interstitial pneumonitis. J Bras Pneumol 39(5):613–619PubMedCentralCrossRefPubMedGoogle Scholar
  4. Cha SI, Choi KJ, Shin KM, Lim J, Yoo SS, Lee J, Lee SY, Kim CH, Park JY (2013) Risk factors for rituximab-induced interstitial lung diseases in patients with malignant lymphoma. Respiration 85(2):175CrossRefPubMedGoogle Scholar
  5. Choueiri TK, Mayer EL, Je Y et al (2011) Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol 29(6):632–638CrossRefPubMedGoogle Scholar
  6. Cleverly J, Screaton N, Hiorns M, Flint JD, Mueller NL (2002) Drug induced lung disease: high-resolution CT and histologic findings. Clin Radiol 57(4):292–299CrossRefGoogle Scholar
  7. Dimopoulou I, Bamias A, Lyberopoulos P, Dimopoulos MA (2006) Pulmonary toxicity from novel antineoplastic agents. Ann Oncol 17(3):372–379CrossRefPubMedGoogle Scholar
  8. Dy GK, Adjei AA (2013) Understanding, recognizing and managing toxicities of targeted anticancer therapies. CA Cancer J Clin 63(4):249–279CrossRefPubMedGoogle Scholar
  9. Ellard SL, Clemons M, Gelmon KA et al (2009) Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol 27(27):4536–4541CrossRefPubMedGoogle Scholar
  10. Ellis SJ, Cleverley JR, Mueller NL (2000) Drug induced lung disease: high resolution CT findings. AJR 175(4):1019–1024CrossRefPubMedGoogle Scholar
  11. Erasmus JJ, McAdams HP, Rossi SE (2002) Drug induced lung injury. Semin Roentgenol 37(1):72–81CrossRefPubMedGoogle Scholar
  12. Foucher P, Camus P (2008) Pneumotox online: the drug induced lung diseases. See: www.pneumotox.com
  13. Hall PS, Harshman LC, Srinivas S, Witteles RM (2013) The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail 1(1):72–78CrossRefPubMedGoogle Scholar
  14. Helman DL Jr, Byrd JC, Ales NC, Shorr AF (2002) Fludarabine-related pulmonary toxicity: a distinct clinical entity in chronic lymphoproliferative syndromes. Chest 122(3):785–790CrossRefPubMedGoogle Scholar
  15. Hitchen L (2006) Adverse drug reactions result in 250.000 UK admissions a year. BMJ 332(7550):1109PubMedCentralCrossRefPubMedGoogle Scholar
  16. Iacovelli R, Palazzo A, Mezi S, Morano F, Naso G, Cortesi E (2012) Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials. Acta Oncol 51(7):873–879CrossRefPubMedGoogle Scholar
  17. Ioka T, Katayama K, Tanaka S, Takakura R, Ashida R, Kobayashi N, Taniai H (2013) Safety and effectiveness of gemcitabine in 855 patients with pancreatic cancer under Japanese clinical practice based on post-marketing surveillance in Japan. Jpn J Clin Oncol 43(2):139–4015CrossRefPubMedGoogle Scholar
  18. Iu X, Hong XN, Gu YJ, Wang BY, Luo ZG, Cao J (2008) Interstitial pneumonitis during rituximab-containing chemotherapy for non-Hodgkin lymphoma. Leuk Lymphoma 49(9):1778–1783CrossRefGoogle Scholar
  19. Kang HJ, Park JS, Kim DW et al (2012) Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients. Respir Med 106(3):443–450CrossRefPubMedGoogle Scholar
  20. Kudoh S, Kato H, Nishiwaki Y et al (2008) Japan Thoracic Radiology group interstitial lung disease in patients with lung cancer: a cohort and nested case-control study. Am J Resp Crit Care Med 177(12):1348–1357CrossRefPubMedGoogle Scholar
  21. Limper A, Rosenow E (1996) Drug induced interstitial lung disease. Curr Opin Pulm Med 2(5):396–404CrossRefPubMedGoogle Scholar
  22. Lioté H, Lioté F, Séroussi B, Mayaud C, Cadranel J (2010) Rituximab-induced lung disease: a systematic literature review. Eur Respir J 35(3):681–687CrossRefPubMedGoogle Scholar
  23. Mueller NL, White DA, Jiang H, Gemma A (2004) Diagnosis and management of drug associated interstitial lung disease. Br J Cancer 91(Suppl 2):S24–S30CrossRefGoogle Scholar
  24. Myers JL, Limper AH, Swensen SJ (2003) Drug induced lung disease: a pragmatic classification incorporating HRCT appearances. Sem Resp Crit Care Med 24(4):445–454CrossRefGoogle Scholar
  25. Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300(19):2277–2285CrossRefPubMedGoogle Scholar
  26. Nicolaides NC, Sass PM, Grasso L (2010) Advances in targeted therapeutic agents. Expert Opin Drug Discov 5(11):1123–1140CrossRefPubMedGoogle Scholar
  27. Nieuwenhuizen L, Verzijlbergen FJ, Wiltink E, Grutters JC, Biesma DH (2008) A possible role of 18F-FDG positron-emission tomography scanning in the early detection of rituximab-induced pneumonitis in patients with non-Hodgkin’s lymphoma. Haematologica 93(8):1267–1269CrossRefPubMedGoogle Scholar
  28. Nozawa M, Ohzeki T, Tamada S et al (2015) Differences in adverse event profiles between everolimus and temsirolimus and the risk factors for non-infectious pneumonitis in advanced renal cell carcinoma. J Immunother 38(7):285–91. doi:  10.1097/CJI.0000000000000090
  29. Oya N, Sasai K, Tachiiri S et al (2006) Influence of radiation dose rate and lung dose on interstitial pneumonitis after fractionated total body irradiation: acute parotitis may predict interstitial pneumonitis. Int J Hematol 83(1):86–91CrossRefPubMedGoogle Scholar
  30. Peddi PF, Shatsky RA, Hurvitz SA (2014) Noninfectious pneumonitis with the use of mTOR inhibitors in breast cancer. Cancer Treat Rev 40(2):320–326CrossRefPubMedGoogle Scholar
  31. Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC (2000) Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 20:1245–1259CrossRefPubMedGoogle Scholar
  32. Satoh T, Gemma A, Kudoh S et al (2014) Incidence and clinical features of drug induced lung injury in patients with advanced colorectal cancer receiving cetuximab: results of a prospective multicenter registry. Jap J Clin Oncol 44(11):1032–3039CrossRefGoogle Scholar
  33. Schwaiblmair M, Behr W, Haeckel T et al (2012) Drug induced interstitial lung disease. Open Respir Med J 6:63–74PubMedCentralCrossRefPubMedGoogle Scholar
  34. Senkus E, Jassem J (2011) Cardiovascular effects of systemic cancer treatment. Cancer Treat Rev 37(4):300–311CrossRefPubMedGoogle Scholar
  35. Shi L, Tang J, Tong L, Liu Z (2014) Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: a systematic review and meta-analysis of clinical trials. Lung Cancer 83(2):231–239CrossRefPubMedGoogle Scholar
  36. Silva CIS, Mueller NL (2006) Drug induced lung diseases: most common reaction patterns and corresponding high-resolution CT manifestations. Semin Ultrasound CT MR 27:111–116CrossRefPubMedGoogle Scholar
  37. Simpson A, Paul J, Graham J et al (1998) Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-1995: a review of patients with germ cell tumors. Br J Cancer 78(8):1061–1066PubMedCentralCrossRefPubMedGoogle Scholar
  38. Tamura M, Saraya T, Fujiwara M et al (2013) High-resolution computed tomography findings for patients with drug induced pulmonary toxicity, with special reference to hypersensitivity pneumonitis-like patterns in gemcitabine-induced cases. Oncologist 18(4):454–459PubMedCentralCrossRefPubMedGoogle Scholar
  39. Vahid B, Marik PE (2008) Pulmonary complications of novel antineoplastic agents for solid tumors. Chest 133(2):528–538CrossRefPubMedGoogle Scholar
  40. Walsh SL, Hansell DM (2014) High-resolution CT of interstitial lung disease: a continuous evolution. Semin Respir Crit Care Med 35(1):129–144CrossRefPubMedGoogle Scholar
  41. White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH (2009) Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001). J Thorac Oncol 4(11):1357–1363CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Rianne Wittenberg
    • 1
  • Santiago Rossi
    • 2
  • Cornelia Schaefer-Prokop
    • 1
    • 3
  1. 1.Department of RadiologyMeander Medical CenterAmersfoortThe Netherlands
  2. 2.Centro de Diagnostico Dr Enrique RossiBuenos AiresArgentina
  3. 3.Department of RadiologyRadboud University Medical CenterNijmegenThe Netherlands

Personalised recommendations