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Early and Late Responses to Ion Irradiation

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Ion Beam Therapy

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL,volume 320))

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Abstract

Early and late responses to ion beam therapy (IBT) are the result of complex interactions between host, dose volume, and radiobiological factors. Our understanding of these early and late tissue responses has improved greatly with the accumulation of laboratory and clinical experience with proton and heavy ion irradiation. With photon therapy becoming increasingly conformal, many concepts developed for 3D conformal radiotherapy and intensity modulated radiation therapy with photons are also applicable to IBT. This chapter reviews basic concepts and experimental data of early and late tissue responses to protons and ions.

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References

  1. H.B. Stone, C.N. Coleman, M.S. Anscher, W.H. McBride, Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 4, 529–536 (2003)

    Article  Google Scholar 

  2. P. Rubin, C.J. Johnston, J.P. Williams, et al., A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int. J. Radiat. Oncol. Biol. Phys. 33, 99–109 (1995)

    Article  Google Scholar 

  3. Z.A. Haroon, J.A. Raleigh, C.S. Greenberg, et al., Early wound healing exhibits cytokine surge without evidence of hypoxia. Ann. Surg. 231, 137–147 (2000)

    Article  Google Scholar 

  4. K.C. Flanders, Smad3 as a mediator of fibrotic response. Int. J. Exp. Pathol. 85, 47–64 (2004)

    Article  Google Scholar 

  5. W. Dörr, K. Spekl, C.L. Farrell, Amelioration of acute oral mucositis by keratinocyte growth factor: Fractionated irradiation. Int. J. Radiat. Oncol. Biol. Phys. 54, 245–251 (2002)

    Google Scholar 

  6. A.B. Roberts, E. Piek, E.P. Böttinger, et al., Is Smad3 a major player in signal transduction pathways leading to fibrogenesis? Chest 120, S43–S47 (2001)

    Article  Google Scholar 

  7. B. Emami, J. Lyman, A. Brown, et al., Tolerance of normal tissue to therapeutic irradiation. Int. J. Radiat. Oncol. Biol. Phys. 21, 109–122 (1991)

    Google Scholar 

  8. T.E. Schultheiss, C.G. Orton, R.A. Peck, Models in radiotherapy: volume effects. Med. Phys. 10, 410–415 (1983)

    Article  Google Scholar 

  9. H.R. Withers, J.M. Taylor, B. Maciejewski, Treatment volume and tissue tolerance. Int. J. Radiat. Oncol. Biol. Phys. 14, 751–759 (1988)

    Article  Google Scholar 

  10. P. Källman, A. Agren, A. Brahme, Tumour and normal tissue responses to fractionated non-uniform dose delivery. Int. J. Radiat. Biol. 62, 249–262 (1992)

    Article  Google Scholar 

  11. G. Gagliardi, I. Lax, A. Ottolenghi, et al., Long-term cardiac mortality after radiotherapy of breast cancer – application of the relative seriality model. Br. J. Radiol. 69, 839–846 (1996)

    Article  Google Scholar 

  12. F. Eriksson, G. Gagliardi, A. Liedberg, et al., Long-term cardiac mortality following radiation therapy for Hodgkin’s disease: analysis with the relative seriality model. Radiother. Oncol. 55, 153–162 (2000)

    Article  Google Scholar 

  13. J.T. Lyman, Complication probability as assessed from dose-volume histograms. Radiat. Res. 8, S13–S19 (1985)

    Article  Google Scholar 

  14. C. Burman, G.J. Kutcher, B. Emami, et al, Fitting of normal tissue tolerance data to an analytic function. Int. J. Radiat. Oncol. Biol. Phys. 21, 123–135 (1991)

    Google Scholar 

  15. G.J. Kutcher, C. Burman, L. Brewster, et al., Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21, 137–146 (1991)

    Google Scholar 

  16. A. Niemierko, Reporting and analyzing dose distributions: a concept of equivalent uniform dose. Med. Phys. 24, 103–110 (1997)

    Article  Google Scholar 

  17. L. Marucci, A. Niemierko, N.J. Liebsch, et al., Spinal cord tolerance to high-dose fractionated 3D conformal proton-photon irradiation as evaluated by equivalent uniform dose and dose volume histogram analysis. Int. J. Radiat. Oncol. Biol. Phys. 59, 551–555 (2004)

    Article  Google Scholar 

  18. J.O. Deasy, A. Niemierko, D. Herbert, et al., Methodological issues in radiation dose-volume outcome analyses: summary of a joint AAPM/NIH workshop. Med. Phys. 29, 2109–2127 (2002)

    Article  Google Scholar 

  19. L. Cozzi, A. Fogliata, A. Lomax, et al., A treatment planning comparison of 3D conformal therapy, intensity modulated photon therapy and proton therapy for treatment of advanced head and neck tumours. Radiother. Oncol. 61, 287–297 (2001)

    Article  Google Scholar 

  20. A. Fogliata, A. Bolsi, and L. Cozzi, Critical appraisal of treatment techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast. Radiother. Oncol. 62, 137–145 (2002)

    Article  Google Scholar 

  21. A. Jackson, L.B. Marks, S.M. Bentzen, et al., The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int. J. Radiat. Oncol. Biol. Phys. 76, S155–S160 (2010)

    Article  Google Scholar 

  22. International Commission on Radiation Units and Measurements, Prescribing, recording, and reporting proton-beam therapy. J. ICRU. 7, Report 78 (2007)

    Google Scholar 

  23. International Atomic Energy Agency and International Commission on Radiation Units and Measurements. Relative Biological Effectiveness in Ion Beam Therapy. Technical Report Series no 461 (International Atomic Energy Agency, Vienna, 2008)

    Google Scholar 

  24. International Atomic Energy Agency, International Commission on Radiation Units and Measurements. Microdosimetry, ICRU Report 36 (ICRU, Bethesda, MD, 1983)

    Google Scholar 

  25. T. Loncol, V. Cosgrove, J.M. Denis, et al., Radiobiological effectiveness of radiation beams with broad LET spectra: Microdosimetric analysis using biological weighting factors. Radiat. Prot. Dosim. 52, 347–352 (1994)

    Google Scholar 

  26. M. Scholz, A.M. Kellerer, W. Kraft-Weyrather, G. Kraft, Computation of cell survival in heavy ion beams for therapy. The model and its approximation. Radiat. Environ. Biophys. 36, 59–66 (1997)

    Article  Google Scholar 

  27. R.B. Hawkins, A microdosimetric-kinetic model for the effect of non-Poisson distribution of lethal lesions on the variation of RBE with LET. Radiat. Res. 160, 61–69 (2003)

    Article  ADS  Google Scholar 

  28. J.J. Wilkens, U. Oelfke, A phenomenological model for the relative biological effectiveness in therapeutic proton beams. Phys. Med. Biol. 49, 2811–2825 (2004)

    Article  Google Scholar 

  29. T. Elsässer, M. Krämer, M. Scholz, Accuracy of the local effect model for the prediction of biologic effects of carbon ion beams in vitro and in vivo. Int. J. Radiat. Oncol. Biol. Phys. 71, 866–872 (2008)

    Google Scholar 

  30. J.W. Hopewell, J. Nyman, I. Turesson, Time factor for acute tissue reactions following fractionated irradiation: a balance between repopulation and enhanced radiosensitivity. Int. J. Radiat. Biol. 79, 513–524 (2003)

    Article  Google Scholar 

  31. S.L. Tucker, Pitfalls in estimating the influence of overall treatment time on local tumor control. Acta Oncol. 38, 171–178 (1999)

    Article  Google Scholar 

  32. H.D. Thames, W. D’Souza, D.A. Kuban, Dual radiobiological interpretations of retrospective clinical data: the time factor. Int. J. Radiat. Biol. 79, 503–509 (2003)

    Article  Google Scholar 

  33. R.G. Dale, J.H. Hendry, B. Jones, et al., Practical methods for compensating for missed treatment days in radiotherapy, with particular reference to head and neck schedules. Clin. Oncol. (R. Coll. Radiol.) 14, 382–393 (2002)

    Google Scholar 

  34. R.J. Berry, G. Schwarz, R.E. Ellis, et al., The effect of hypoxia on the skin response of mice to divided doses of 15 MeV electrons. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 12, 293–296 (1967)

    Article  Google Scholar 

  35. B.G. Douglas, J.F. Fowler, The effect of multiple small doses of x rays on skin reactions in the mouse and a basic interpretation. Radiat. Res. 66, 401–426 (1976)

    Article  Google Scholar 

  36. S.G. Raju, M.R. Carpenter, A heavy particle comparative study. Part IV: acute and late reactions. Br. J. Radiol. 51, 720–727 (1978)

    Google Scholar 

  37. J. Tepper, L. Verhey, M. Goitein, H.D. Suit, In vivo determinations of RBE in a high energy modulated proton beam using normal tissue reactions and fractionated dose schedules. Int. J. Radiat. Oncol. Biol. Phys. 2, 1115–1122 (1977)

    Article  Google Scholar 

  38. K. Nemoto, T. Pickles, A.I. Minchinton, G.K. Lam, The relative biological effectiveness of the modulated proton beam at TRIUMF. Radiat. Med. 16, 43–46 (1998)

    Google Scholar 

  39. K. Ando, S. Koike, K. Nojima, et al., Mouse skin reactions following fractionated irradiation with carbon ions. Int. J. Radiat. Biol. 74, 129–138 (1998)

    Article  Google Scholar 

  40. T. Zacharias, W. Dörr, W. Enghardt, et al., Acute response of pig skin to irradiation with12C-ions or 200 kV X-rays. Acta Oncol. 36, 637–642 (1997)

    Article  Google Scholar 

  41. K. Kagawa, M. Murakami, Y. Hishikawa, et al., Preclinical biological assessment of proton and carbon ion beams at Hyogo Ion Beam Medical Center. Int. J. Radiat. Oncol. Biol. Phys. 54, 928–938 (2002)

    Article  Google Scholar 

  42. H.R. Withers, M.M. Elkind, Microcolony survival assay for cells of mouse intestinal mucosa exposed to radiation. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 17, 261–267 (1970)

    Article  Google Scholar 

  43. K. Kagawa, M. Murakami, Y. Hishikawa, et al., Preclinical biological assessment of proton and carbon ion beams at Hyogo Ion Beam Medical Center. Int. J. Radiat. Oncol. Biol. Phys. 54, 928–938 (2002)

    Article  Google Scholar 

  44. J. Gueulette, L. Böhm, B.M. De Coster, et al., RBE variation as a function of depth in the 200-MeV proton beam produced at the National Accelerator Centre in Faure (South Africa). Radiother. Oncol. 42, 303–309 (1997)

    Article  Google Scholar 

  45. J. Gueulette, J.P. Slabbert, L. Böhm, et al., Proton RBE for early intestinal tolerance in mice after fractionated irradiation. Radiother. Oncol. 61,177–184 (2001)

    Article  Google Scholar 

  46. E.L. Alpen, P. Powers-Risius, M. McDonald, Survival of intestinal crypt cells after exposure to high Z, high-energy charged particles. Radiat. Res. 83, 677–687 (1980)

    Article  Google Scholar 

  47. L.S. Goldstein, T.L. Phillips, G.Y. Ross, Biological effects of accelerated heavy ions. II. Fractionated irradiation of intestinal crypt cells. Radiat. Res. 86, 542–558 (1981)

    Google Scholar 

  48. K. Fukutsu, T. Kanai, Y. Furusawa, K. Ando, Response of mouse intestine after single and fractionated irradiation with accelerated carbon ions with a spread-out Bragg peak. Radiat. Res. 148, 168–174 (1997)

    Article  Google Scholar 

  49. K.H. Woodruff, J.T. Leith, P. Powers-Risius, et al., Comparison of heavy particle withX-irradiation on the hamster lung. Am. J. Pathol. 95, 765–774 (1979)

    Google Scholar 

  50. J. Gueulette, L. Böhm, J.P. Slabbert, et al., Proton relative biological effectiveness (RBE) for survival in mice after thoracic irradiation with fractionated doses. Int. J. Radiat. Oncol. Biol. Phys. 47, 1051–1058 (2000)

    Article  Google Scholar 

  51. W. Dörr, H. Alheit, S. Appold, et al., Response of pig lung to irradiation with accelerated 12C-ions. Radiat. Environ. Biophys. 38, 185–194 (1999)

    Article  Google Scholar 

  52. J.T. Leith, K.H. Woodruff, B.S. Lewinsky, et al., Letter: Tolerance of the spinal cord of rats to irradiation with neon ions. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 28, 393–398 (1975)

    Article  Google Scholar 

  53. J.T. Leith, K.H. Woodruff, J. Howard, et al., Early and late effects of accelerated charged particles on normal tissues. Int. J. Radiat. Oncol. Biol. Phys. 3, 103–108 (1977)

    Article  Google Scholar 

  54. J.T. Leith, M. McDonald, P. Powers-Risius, et al., Response of rat spinal cord to single and fractionated doses of accelerated heavy ions. Radiat. Res. 89, 176–193 (1982)

    Article  Google Scholar 

  55. H.P. Bijl, P. van Luijk, R.P. Coppes, et al., Dose-volume effects in the rat cervical spinal cord after proton irradiation. Int. J. Radiat. Oncol. Biol. Phys. 52, 205–211 (2002)

    Article  Google Scholar 

  56. H.P. Bijl, P. van Luijk, R.P. Coppes, et al., Unexpected changes of rat cervical spinal cord tolerance caused by inhomogeneous dose distributions. Int. J. Radiat. Oncol. Biol. Phys. 57, 274–281 (2003)

    Article  Google Scholar 

  57. H.P. Bijl, P. van Luijk, R.P. Coppes, et al., Influence of adjacent low-dose fields on tolerance to high doses of protons in rat cervical spinal cord. Int. J. Radiat. Oncol. Biol. Phys. 64,1204–1210 (2006)

    Article  Google Scholar 

  58. M.E. Philippens, L.A. Pop, A.G. Visser, et al., Bath and shower effect in spinal cord: the effect of time interval. Int. J. Radiat. Oncol. Biol. Phys. 73, 514–522 (2009)

    Article  Google Scholar 

  59. J. Debus, M. Scholz, T. Haberer, et al., Radiation tolerance of the rat spinal cord after single and split doses of photons and carbon ions. Radiat. Res. 160, 536–542 (2003)

    Article  Google Scholar 

  60. C.P. Karger, P. Peschke, R. Sanchez-Brandelik, et al., Radiation tolerance of the rat spinal cord after 6 and 18 fractions of photons and carbon ions: experimental results and clinical implications. Int. J. Radiat. Oncol. Biol. Phys. 66, 1488–1497 (2006)

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Medicine, Loma Linda University Medical Center, 11234 Anderson Street, B 121, Loma Linda, CA, 92354, USA

    Reinhard Schulte & Ted Ling

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  1. Reinhard Schulte
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  2. Ted Ling
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Correspondence to Reinhard Schulte .

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  1. Forschungszentrum Jülich, Jülich, 52425, Germany

    Ute Linz

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Schulte, R., Ling, T. (2012). Early and Late Responses to Ion Irradiation. In: Linz, U. (eds) Ion Beam Therapy. Biological and Medical Physics, Biomedical Engineering, vol 320. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21414-1_5

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  • DOI: https://doi.org/10.1007/978-3-642-21414-1_5

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