Seminars in Radiation Oncology
Volume 17, Issue 2 , Pages 89-98 , April 2007

Using Biological Markers to Predict Risk of Radiation Injury

  • Katharina Fleckenstein, MD

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham NC.
    • Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
    • ,
  • Benjamin Gauter-Fleckenstein, MD

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham NC.
    • Department of Anaesthesiology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
    • ,
  • Isabel L. Jackson, BS

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham NC.
    • ,
  • Zahid Rabbani, MD

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham NC.
    • ,
  • Mitchell Anscher, MD

      Affiliations

    • Department of Radiation Oncology, Virginia Commonwealth University School of Medicine, Richmond, VA.
    • ,
  • Zeljko Vujaskovic, MD, PhD

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham NC.
    • Corresponding Author InformationAddress reprint requests to Zeljko Vujaskovic, MD, PhD, Department of Radiation Oncology, DUMC, Box 3455, Durham, NC 27710.

References 

  1. Mehta V. Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: Pulmonary function, prediction, and prevention. Int J Radiat Oncol Biol Phys. 2005;63:5–24
  2. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–122
  3. Willner J, Baier K, Caragiani E, et al. Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2002;52:382–389
  4. Rodrigues G, Lock M, D’Souza D, et al. Prediction of radiation pneumonitis by dose-volume histogram parameters in lung cancer—A systematic review. Radiother Oncol. 2004;71:127–138
  5. Castellino RA, Glatstein E, Turbow MM, et al. Latent radiation injury of lungs or heart activated by steroid withdrawal. Ann Intern Med. 1974;80:593–599
  6. Morgan GW, Breit SN. Radiation and the lung: A reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys. 1995;31:361–369
  7. Rubin P, Shapiro DL, Finklestein JN, et al. The early release of surfactant following lung irradiation of alveolar type II cells. Int J Radiat Oncol Biol Phys. 1980;6:75–77
  8. Vujaskovic Z, Anscher MS, Feng QF, et al. Radiation-induced hypoxia may perpetuate late normal tissue injury. Int J Radiat Oncol Biol Phys. 2001;50:851–855
  9. Herskind C, Bamberg M, Rodemann HP. The role of cytokines in the development of normal-tissue reactions after radiotherapy. Strahlenther Onkol. 1998;174(suppl 3):12–15
  10. Rube CE, Uthe D, Wilfert F, et al. The bronchiolar epithelium as a prominent source of pro-inflammatory cytokines after lung irradiation. Int J Radiat Oncol Biol Phys. 2005;61:1482–1492
  11. 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;33:99–109
  12. Vujaskovic Z, Marks LB, Anscher MS. The physical parameters and molecular events associated with radiation-induced lung toxicity. Semin Radiat Oncol. 2000;10:296–307
  13. Johnston CJ, Williams JP, Elder A, et al. Inflammatory cell recruitment following thoracic irradiation. Exp Lung Res. 2004;30:369–382
  14. Rubin P, Finkelstein J, Shapiro D. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: Interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys. 1992;24:93–101
  15. Sun Y, Oberley LW. Redox regulation of transcriptional activators. Free Radic Biol Med. 1996;21:335–348
  16. Wu X, Bishopric NH, Discher DJ, et al. Physical and functional sensitivity of zinc finger transcription factors to redox change. Mol Cell Biol. 1996;16:1035–1046
  17. Schmidt-Ullrich RK, Dent P, Grant S, et al. Signal transduction and cellular radiation responses. Radiat Res. 2000;153:245–257
  18. Martin M, Lefaix J, Delanian S. TGF-beta1 and radiation fibrosis: A master switch and a specific therapeutic target?. Int J Radiat Oncol Biol Phys. 2000;47:277–290
  19. Rube CE, Uthe D, Schmid KW, et al. Dose-dependent induction of transforming growth factor beta (TGF-beta) in the lung tissue of fibrosis-prone mice after thoracic irradiation. Int J Radiat Oncol Biol Phys. 2000;47:1033–1042
  20. Yi ES, Bedoya A, Lee H, et al. Radiation-induced lung injury in vivo: Expression of transforming growth factor-beta precedes fibrosis. Inflammation. 1996;20:339–352
  21. Hakenjos L, Bamberg M, Rodemann HP. TGF-beta1-mediated alterations of rat lung fibroblast differentiation resulting in the radiation-induced fibrotic phenotype. Int J Radiat Biol. 2000;76:503–509
  22. Haroon ZA, Amin K, Jiang X, et al. A novel role for erythropoietin during fibrin-induced wound-healing response. Am J Pathol. 2003;163:993–1000
  23. Moeller BJ, Cao Y, Vujaskovic Z, et al. The relationship between hypoxia and angiogenesis. Semin Radiat Oncol. 2004;14:215–221
  24. Shweiki D, Itin A, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359:843–845
  25. 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;41:1029–1035
  26. Anscher MS, Kong FM, Marks LB, et al. Changes in plasma transforming growth factor beta during radiotherapy and the risk of symptomatic radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys. 1997;37:253–258
  27. Anscher MS, Murase T, Prescott DM, et al. Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis. Int J Radiat Oncol Biol Phys. 1994;30:671–676
  28. Anscher MS, Marks LB, Shafman TD, et al. Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation. J Clin Oncol. 2001;19:3758–3765
  29. 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;56:988–995
  30. Fu XL, Huang H, Bentel G, et al. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V(30) and transforming growth factor beta. Int J Radiat Oncol Biol Phys. 2001;50:899–908
  31. Kong FM, Anscher MS, Sporn TA, et al. Loss of heterozygosity at the mannose 6-phosphate insulin-like growth factor 2 receptor (M6P/IGF2R) locus predisposes patients to radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2001;49:35–41
  32. Dennis PA, Rifkin DB. Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor. Proc Natl Acad Sci U S A. 1991;88:580–584
  33. Kornfeld S. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem. 1992;61:307–330
  34. De Jaeger K, Seppenwoolde Y, Kampinga HH, et al. Significance of plasma transforming growth factor-beta levels in radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004;58:1378–1387
  35. Jeremic B, Hennig M, Zimmermann FB. Predictors of radiation pneumonitis after radiotherapy in lung cancer. Int J Radiat Oncol Biol Phys. 2005;61:302
  36. Vujaskovic Z, Groen HJ. TGF-beta, radiation-induced pulmonary injury and lung cancer. Int J Radiat Biol. 2000;76:511–516
  37. Novakova-Jiresova A, Van Gameren MM, Coppes RP, et al. Transforming growth factor-beta plasma dynamics and post-irradiation lung injury in lung cancer patients. Radiother Oncol. 2004;71:183–189
  38. Marks LB, Munley MT, Bentel GC, et al. Physical and biological predictors of changes in whole-lung function following thoracic irradiation. Int J Radiat Oncol Biol Phys. 1997;39:563–570
  39. Chen Y, Williams J, Ding I, et al. Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol. 2002;12:26–33
  40. Barthelemy-Brichant N, Bosquee L, Cataldo D, et al. Increased IL-6 and TGF-beta1 concentrations in bronchoalveolar lavage fluid associated with thoracic radiotherapy. Int J Radiat Oncol Biol Phys. 2004;58:758–767
  41. Anscher MS, Peters WP, Reisenbichler H, et al. Transforming growth factor beta as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. N Engl J Med. 1993;328:1592–1598
  42. Murase T, Jirtle RL, McDonald GB. Transforming growth factor-beta plasma concentrations in patients with leukemia and lymphoma receiving chemoradiotherapy and marrow transplantation. Blood. 1994;83:2383
  43. van Waarde MA, van Assen AJ, Kampinga HH, et al. Quantification of transforming growth factor-beta in biological material using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct. Anal Biochem. 1997;247:45–51
  44. National Cancer Institute Common Toxicity Criteria, Bethesda version 2.0. 2003;
  45. LENT SOMA tables. Radiother Oncol. 1995;35:17–60
  46. Arpin D, Perol D, Blay JY, et al. Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis. J Clin Oncol. 2005;23:8748–8756
  47. Chen Y, Rubin P, Williams J, et al. Circulating IL-6 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2001;49:641–648
  48. Chen Y, Hyrien O, Williams J, et al. Interleukin (IL)-1A and IL-6: Applications to the predictive diagnostic testing of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2005;62:260–266
  49. Hart JP, Broadwater G, Rabbani Z, et al. Cytokine profiling for prediction of symptomatic radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2005;63:1448–1454
  50. Kohno N, Kyoizumi S, Awaya Y, et al. New serum indicator of interstitial pneumonitis activity (Sialylated carbohydrate antigen KL-6). Chest. 1989;96:68–73
  51. Kohno N, Hamada H, Fujioka S, et al. Circulating antigen KL-6 and lactate dehydrogenase for monitoring irradiated patients with lung cancer. Chest. 1992;102:117–122
  52. Goto K, Kodama T, Sekine I, et al. Serum levels of KL-6 are useful biomarkers for severe radiation pneumonitis. Lung Cancer. 2001;34:141–148
  53. Matsuno Y, Satoh H, Ishikawa H, et al. Simultaneous measurements of KL-6 and SP-D in patients undergoing thoracic radiotherapy. Med Oncol. 2006;23:75–82
  54. Hara R, Itami J, Komiyama T, et al. Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors. Chest. 2004;125:340–344
  55. Kobayashi J, Kitamura S. KL-6: A serum marker for interstitial pneumonia. Chest. 1995;108:311–315
  56. Sasaki R, Soejima T, Matsumoto A, et al. Clinical significance of serum pulmonary surfactant proteins a and d for the early detection of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2001;50:301–307
  57. Takahashi H, Imai Y, Fujishima T, et al. Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis. Eur Respir J. 2001;17:481–487
  58. Susskind H, Hymowitz MH, Lau YH, et al. Increased plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy. Int J Radiat Oncol Biol Phys. 2003;56:1161–1169
  59. Ishii Y, Kitamura S. Soluble intercellular adhesion molecule-1 as an early detection marker for radiation pneumonitis. Eur Respir J. 1999;13:733–738
  60. Hoeller U, Tribius S, Kuhlmey A, et al. Increasing the rate of late toxicity by changing the score? (A comparison of RTOG/EORTC and LENT/SOMA scores). Int J Radiat Oncol Biol Phys. 2003;55:1013–1018
  61. Maasilta P, Salonen EM, Vaheri A, et al. Procollagen-III in serum, plasminogen activation and fibronectin in bronchoalveolar lavage fluid during and following irradiation of human lung. Int J Radiat Oncol Biol Phys. 1991;20:973–980

 Supported in part by the DFG (German Research Society), Research Fellowship Grant for Katharina Fleckenstein (FL551/1-1) and by the NIH, RO1 # CA 098452 (PI: Zeljko Vujaskovic).

PII: S1053-4296(06)00105-6

doi: 10.1016/j.semradonc.2006.11.004

Seminars in Radiation Oncology
Volume 17, Issue 2 , Pages 89-98 , April 2007

Article Tools

* Image Usage & Resolution