Radiation Response of the Normal Lung Tissue and Lung Tumors

Part of the Medical Radiology book series (MEDRAD)


We reviewed recent investigations on radiation response of normal lung tissue and lung tumors and also introduced our own investigations. The mechanisms for response of normal lung tissues to radiation are not yet fully understood. Recent researches have revealed that various cytokines and lung parenchymal cells are involved in the pathogenesis of radiation response of normal lung tissues. Prediction of tumor and/or normal tissue sensitivity to treatment is being investigated for tailor-made cancer treatment based on the biological characteristics. In the near future, it is hoped that the relationship among clonogenic death of target cells, cytokine induction, gene expression and radiation pneumonitis, and that among radiosensitivity, tumor histology, tumor gene expression and patient characteristics will be clarified. Future investigations will lead to a step toward an era of personalized cancer treatment.


Local Control Rate Primary Lung Cancer Normal Lung Tissue Radiation Pneumonitis Radiation Response 


  1. Anscher MS, Marks LB, Shafman TD et al (2003) Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy. Int J Radiat Oncol Biol Phys 56:988–995PubMedCrossRefGoogle Scholar
  2. Baba F, Shibamoto Y, Ogino H et al (2010) Clinical outcomes of stereotactic body radiotherapy for stage I non-small cell lung cancer using different doses depending on tumor size. Radiat Oncol 5:81PubMedCrossRefGoogle Scholar
  3. Barton HL, Mcgrahan GM Jr, Jordan GL Jr (1960) The evaluation of roentgen therapy in the management of non-resectable carcinoma of the lung. Dis Chest 37:170–175PubMedCrossRefGoogle Scholar
  4. Bergmann M, Graham EA (1951) Pneumonectomy for severe irradiation damage of the lung. J Thorac Surg 22:549–567PubMedGoogle Scholar
  5. British Thoracic Society (1998) BTS recommendations to respiratory physicians for organising the care of patients with lung cancer. The lung cancer working party of the British thoracic society standards of care committee. Thorax 53:S1–S8Google Scholar
  6. Brodin O, Lennartsson L, Nilsson S (1991) Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro. Acta Oncol 30:967–974PubMedCrossRefGoogle Scholar
  7. Chen Z, King W, Pearcey R, Kerba M, Mackillop WJ (2008) The relationship between waiting time for radiotherapy and clinical outcomes: a systematic review of the literature. Radiother Oncol 87:3–16PubMedCrossRefGoogle Scholar
  8. Engelstad RB (1940) Pulmonary lesions after roentgen and radium irradiation. Am J Roentgenol 43:676Google Scholar
  9. Goto K, Kodama T, Sekine I et al (2001) Serum levels of KL-6 are useful biomarkers for severe radiation pneumonitis. Lung Cancer 34:141–148PubMedCrossRefGoogle Scholar
  10. Groover TA, Christie AC, Merritt EA (1923) Intrathoracic changes following roentgen treatment of breast carcinoma. Am J Roentgenol 10:471Google Scholar
  11. Hara R, Itami J, Komiyama T et al (2004) Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors. Chest 125:340–344PubMedCrossRefGoogle Scholar
  12. Herfarth KK, Debus J, Lohr F et al (2001) Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19:164–170PubMedGoogle Scholar
  13. Hilkens J, Ligtenberg MJ, Vos HL et al (1992) Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci 17:359–363PubMedCrossRefGoogle Scholar
  14. Ishikawa A, Suga T, Shoji Y et al (2011) Genetic variants of NPAT-ATM and AURKA are associated with an early adverse reaction in cervical cancer patients after radiation therapy. Int J Radiat Oncol Biol Phys (In press, 2010 Nov 2, Epub ahead of print)Google Scholar
  15. Iwakawa M, Imai T, Harada Y et al (2002) RadGenomic project. J Jpn Radiol Soc 62:484–489Google Scholar
  16. Iwata H, Murakami M, Demizu Y et al (2010) High-dose proton therapy and carbon-ion therapy for stage I nonsmall cell lung cancer. Cancer 116:2476–2485PubMedGoogle Scholar
  17. Jin H, Tucker SL, Liu HH et al (2009) Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy. Radiother Oncol 91:427–432PubMedCrossRefGoogle Scholar
  18. Kang JK, Kim MS, Kim JH et al (2010) Oligometastases confined one organ from colorectal cancer treated by SBRT. Clin Exp Metastasis 27:273–278PubMedCrossRefGoogle Scholar
  19. Katayama N, Sato S, Katsui K et al (2009) Analysis of factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy. Int J Radiat Oncol Biol Phys 73:1049–1054PubMedCrossRefGoogle Scholar
  20. Kim MS, Yoo SY, Cho CK et al (2009) Stereotactic body radiation therapy using three fractions for isolated lung recurrence from colorectal cancer. Oncology 76:212–219PubMedCrossRefGoogle Scholar
  21. Kobayashi J, Kitamura S (1995) KL-6: a serum marker for interstitial pneumonia. Chest 108:311–315PubMedCrossRefGoogle Scholar
  22. Kohno N, Akiyama M, Kyoizumi S et al (1988) Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. Jpn J Clin Oncol 18:203–216PubMedGoogle Scholar
  23. Kohno N, Kyoizumi S, Awaya Y et al (1989) New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 96:68–73PubMedCrossRefGoogle Scholar
  24. Kong FM, Ten Haken R, Eisbruch A, Lawrence TS (2005) Non-small cell lung cancer therapy-related pulmonary toxicity: an update on radiation pneumonitis and fibrosis. Semin Oncol 32:S42–S54PubMedCrossRefGoogle Scholar
  25. Koukourakis M, Hlouverakis G, Kosma L et al (1996) The impact of overall treatment time on the results of radiotherapy for non-small cell lung carcinoma. Int J Radiat Oncol Biol Phys 34:315–322PubMedCrossRefGoogle Scholar
  26. Kruser TJ, Chao ST, Elson P et al (2008) Multidisciplinary management of colorectal brain metastases. A retrospective study. Cancer 113:158–165PubMedCrossRefGoogle Scholar
  27. Kubo A, Osaki K, Kawanaka T et al (2009) Risk factors for radiation pneumonitis caused by whole breast irradiation following breast-conserving surgery. J Med Invest 56:99–110PubMedCrossRefGoogle Scholar
  28. Kuwano K, Miyazaki H, Hagimoto N et al (1999) The involvement of Fas-Fas ligand pathway in fibrosing lung diseases. Am J Respir Cell Mol Biol 20:53–60PubMedCrossRefGoogle Scholar
  29. Martin TR, Hagimoto N, Nakamura M, Matute-Bello G (2005) Apoptosis and epithelial injury in the lungs. Proc Am Thorac Soc 2:214–220PubMedCrossRefGoogle Scholar
  30. Matsuno Y, Satoh H, Ishikawa H et al (2006) Simultaneous measurements of KL-6 and SP-D in patients undergoing thoracic radiotherapy. Med Oncol 23:75–82PubMedCrossRefGoogle Scholar
  31. Meyners T, Heisterkamp C, Kueter JD et al (2010) Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis. BMC Cancer 10:582PubMedGoogle Scholar
  32. Milano MT, Katz AW, Muhs AG et al (2008) A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions. Cancer 112:650–658PubMedCrossRefGoogle Scholar
  33. Mizoe JE, Tsujii H, Kamada T et al (2004) Dose escalation study of carbon ion radiotherapy for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 60:358–364PubMedCrossRefGoogle Scholar
  34. Murai T, Shibamoto Y, Baba F et al (2010) Cryptogenic organizing pneumonia after stereotactic body radiotherapy of the lung. Int J Radiat Oncol Biol Phys 78:S530–S531CrossRefGoogle Scholar
  35. Murai T, Shibamoto Y, Baba F et al (2011) Progression of non-small-cell lung cancer during the interval before stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys (In press, 2010 Nov 20, Epub ahead of print)Google Scholar
  36. Murakami M, Demizu Y, Niwa Y et al (2009) Current status of the HIBMC, providing particle beam radiation therapy for more than 2,600 patients, and the prospects of laser-driven proton radiotherapy. GermanyMunich, World congress 2009, Medical physics and biomedical engineering (WC 2009) IFMBE proceedings, vol 25/1, pp 878–882. doi:10.1007/978-3-642-03474-9_247 Google Scholar
  37. Ogo E, Komaki R, Fujimoto K et al (2008) A survey of radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy in Japan. Int J Radiat Oncol Biol Phys 71:123–131PubMedCrossRefGoogle Scholar
  38. Penney DP, Siemann DW, Rubin P, Shapiro DL, Finkelstein J, Cooper RA Jr (1982) Morphologic changes reflecting early and late effects of irradiation of the distal lung of the mouse: a review. Scan Electron Microsc Pt 1:413–425Google Scholar
  39. Puck TT, Marcus PI (1956) Action of X-rays on mammalian cells. J Exp Med 103:653–666PubMedCrossRefGoogle Scholar
  40. Quintero M, Brennan PA, Thomas GJ, Moncada S (2006) Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation. Cancer Res 66:770–774PubMedCrossRefGoogle Scholar
  41. Rubin P, Johnson CJ, Williams JP, McDonald S, Finkelstein JN (1995) A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 33:99–109PubMedCrossRefGoogle Scholar
  42. Ruckdeschel JC (1998) Future directions in non-small-cell lung cancer: a continuing perspective. Oncology 12:S90–S96Google Scholar
  43. Rusthoven KE, Kavanagh BD, Burri SH et al (2009) Multiinstitutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol 27:1579–1584PubMedCrossRefGoogle Scholar
  44. Saleh D, Barnes PJ, Giaid A (1997) Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 155:1763–1769PubMedCrossRefGoogle Scholar
  45. Shibamoto Y, Shibata T, Miyatake S et al (1994) Assessment of the proliferative activity and radiosensitivity of human tumours using the cytokinesis-block micronucleus assay. Br J Cancer 70:67–71PubMedCrossRefGoogle Scholar
  46. Shibamoto Y, Ike O, Mizuno H, Fukuse T, Hitomi H, Takahashi M (1998) Proliferative activity and micronucleus frequency after radiation of lung cancer cells as assessed by the cytokinesis-block method and their relationship to clinical outcome. Clin Cancer Res 4:677–682PubMedGoogle Scholar
  47. Stahel RA, Gilks WR, Lehmann HP et al (1994) Third international workshop on lung tumor and differentiation antigens: overview of the results of the central data analysis. Int J Cancer 8:S6–S26CrossRefGoogle Scholar
  48. Suga T, Ishikawa A, Kohda M et al (2007) Halotype-based analysis of genes associated with risk of adverse skin reactions after radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 69:685–693PubMedCrossRefGoogle Scholar
  49. Sweany SK, Moss WT, Haddy FJ (1959) The effects of chest irradiation of pulmonary function. J Clin Invest 38:587–593PubMedCrossRefGoogle Scholar
  50. Takigawa N, Segawa Y, Saeki T et al (2000) Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity. Int J Radiat Oncol Biol Phys 48:751–755PubMedCrossRefGoogle Scholar
  51. Tucker SL, Jin H, Wei X et al (2010) Impact of toxicity grade and scoring system on the relationship between mean lung dose and risk of radiation pneumonitis in a large cohort of patients with non-small cell lung cancer. Int J Radiat Oncol Biol Phys 77:691–698PubMedCrossRefGoogle Scholar
  52. West CML, Davidson SE, Roberts SA, Hunter RD (1997) The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix. Br J Cancer 76:1184–1190PubMedCrossRefGoogle Scholar
  53. Worthington J, Robson T, Murray M, O’Rourke M, Keilty G, Hirst DG (2000) Modification of vascular tone using iNOS under the control of a radiation-inducible promoter. Gene Ther 7:1126–1131PubMedCrossRefGoogle Scholar
  54. Wronski M, Maor MH, Davis BJ et al (1997) External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M.D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys 37:753–759PubMedCrossRefGoogle Scholar
  55. Yamashita H, Kobayashi-Shibata S, Terahara A et al (2010) 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 5:32PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of RadiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan

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