• T. Bostel
  • F. Sterzing
Part of the Medical Radiology book series (MEDRAD)


The focus of this chapter lies on the description of the general basics of early and late radiation effects and the translation of these pathogenetic processes into imaging; furthermore, a few short clinical examples including imaging patterns of those underlying pathogenetic normal tissue reactions are given to provide a better understanding. In addition, the margin concepts used in radiotherapy as well as the important radiation techniques are summarized, as it is very important for diagnostic radiologists to correlate post-therapeutic tissue and organ changes in follow-up examinations with dose characteristics of a certain treatment to achieve a higher degree of reliability in image interpretation. Furthermore, for a better understanding of the cellular basis of the various radiogenic tissue effects, a short refresher about the underlying radiobiological principles is given. The detailed description of specific radiation effects and imaging patterns of clinically relevant organs and tissues, however, follows in the specific organ chapters in order to avoid redundancy.


Planning Target Volume Stereotactic Body Radiation Therapy Oncological Treatment Secondary Cancer Chronic Radiation 
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.



Consequential late effects




Computed tomography


Clinical target volume


Three dimensional


Four dimensional


Deoxyribonucleic acid


External-beam radiation therapy


Exempli gratia


Gross tumor volume




Id est


Interleukin-1 alpha


Inducible nitric oxide synthase


Image-guided radiotherapy


Intensity-modulated radiation therapy


Magnetic resonance imaging


Messenger ribonucleic acid


Normal tissue complication probability


Organs at risk


Positron emission tomography


Planning target volume


Relative biological effectiveness


Relative risk


Stereotactic body radiation therapy


Tolerance dose


Transforming growth factor-ß


Tumor necrosis factor alpha


Veno-occlusive disease


  1. Bentzen SM, Turesson I, Thames HD (1990) Fractionation sensitivity and latency of telangiectasia after postmastectomy radiotherapy: a graded-response analysis. Radiother Oncol 18:95–106CrossRefPubMedGoogle Scholar
  2. Bentzen SM, Constine LS, Deasy JO, Eisbruch A, Jackson A, Marks LB, Ten Haken RK, Yorke ED (2010) Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys 76:S3–S9PubMedCentralCrossRefPubMedGoogle Scholar
  3. Boda-Heggemann J, Lohr F, Wenz F, Flentje M, Guckenberger M (2011) kV cone-beam CT-based IGRT: a clinical review. Strahlenther Onkol 187:284–291CrossRefPubMedGoogle Scholar
  4. Bortfeld T, Jeraj R (2011) The physical basis and future of radiation therapy. Br J Radiol 84:485–498PubMedCentralCrossRefPubMedGoogle Scholar
  5. Boyd TS, Mehta MP (1999) Stereotactic radiosurgery for brain metastases. Oncology 13:1397–1409; discussion, 1409–1410, 1413PubMedGoogle Scholar
  6. Brahme A, Roos JE, Lax I (1982) Solution of an integral equation encountered in rotation therapy. Phys Med Biol 27:1221–1229CrossRefPubMedGoogle Scholar
  7. Brenner DJ, Curtis RE, Hall EJ, Ron E (2000) Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer 88:398–406CrossRefPubMedGoogle Scholar
  8. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y, Early Breast Cancer Trialists’ Collaborative G (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106CrossRefPubMedGoogle Scholar
  9. Constine LS, Friedman D, Morris M, Williams JP, Rubin P, Okunieff P (2013) Chapter 12: Late effects of cancer treatment on normal tissues. In: Halperin EC, Wazer DE, Perez CA, Brady LW (eds) Perez & Brady’s principles and practice of radiation oncology, 6th edn., pp 320–350Google Scholar
  10. de Vathaire F, Hawkins M, Campbell S, Oberlin O, Raquin MA, Schlienger JY, Shamsaldin A, Diallo I, Bell J, Grimaud E, Hardiman C, Lagrange JL, Daly-Schveitzer N, Panis X, Zucker JM, Sancho-Garnier H, Eschwege F, Chavaudra J, Lemerle J (1999) Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment. Br J Cancer 79:1884–1893PubMedCentralCrossRefPubMedGoogle Scholar
  11. Debus J, Engenhart-Cabillic R, Holz FG, Pastyr O, Rhein B, Bortfeld T, Wannenmacher M (1997) Stereotactic precision radiotherapy in the treatment of intraocular malignancies with a micro-multileaf collimator. Front Radiat Ther Oncol 30:39–46CrossRefPubMedGoogle Scholar
  12. Dische S, Warburton MF, Jones D, Lartigau E (1989) The recording of morbidity related to radiotherapy. Radiother Oncol 16:103–108CrossRefPubMedGoogle Scholar
  13. Dittmann K, Mayer C, Rodemann HP (2005) Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol 76:157–161CrossRefPubMedGoogle Scholar
  14. Dorr W (2009) Chapter 13: Pathogenesis of normal-tissue side-effects. In: Joiner M, Van der Kogel A (eds) Basic clinical radiobiology, 4th edn. Hodder Arnold, London, pp 169–190CrossRefGoogle Scholar
  15. Dorr W, Hendry JH (2001) Consequential late effects in normal tissues. Radiother Oncol 61:223–231CrossRefPubMedGoogle Scholar
  16. Dorr W, Bertmann S, Herrmann T (2005) Radiation induced lung reactions in breast cancer therapy. Modulating factors and consequential effects. Strahlenther Onkol 181:567–573CrossRefPubMedGoogle Scholar
  17. Dorr W, Kallfels S, Herrmann T (2013) Late bone and soft tissue sequelae of childhood radiotherapy. Relevance of treatment age and radiation dose in 146 children treated between 1970 and 1997. Strahlenther Onkol 189:529–534CrossRefPubMedGoogle Scholar
  18. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109–122CrossRefPubMedGoogle Scholar
  19. Fajardo LF (2005) The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 44:13–22CrossRefPubMedGoogle Scholar
  20. Gademann G, Schlegel W, Debus J, Schad L, Bortfeld T, Hover KH, Lorenz WJ, Wannenmacher M (1993) Fractionated stereotactically guided radiotherapy of head and neck tumors: a report on clinical use of a new system in 195 cases. Radiother Oncol 29:205–213CrossRefPubMedGoogle Scholar
  21. Goodhead DT (1994) Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. Int J Radiat Biol 65:7–17CrossRefPubMedGoogle Scholar
  22. Gray LH (1957) Oxygenation in radiotherapy. I. Radiobiological considerations. Br J Radiol 30:403–406CrossRefPubMedGoogle Scholar
  23. Guckenberger M, Allgauer M, Appold S, Dieckmann K, Ernst I, Ganswindt U, Holy R, Nestle U, Nevinny-Stickel M, Semrau S, Sterzing F, Wittig A, Andratschke N (2013) Safety and efficacy of stereotactic body radiotherapy for stage 1 non-small-cell lung cancer in routine clinical practice: a patterns-of-care and outcome analysis. J Thorac Oncol 8:1050–1058CrossRefPubMedGoogle Scholar
  24. Haie-Meder C, Siebert FA, Potter R (2011) Image guided, adaptive, accelerated, high dose brachytherapy as model for advanced small volume radiotherapy. Radiother Oncol 100:333–343CrossRefPubMedGoogle Scholar
  25. Hakenjos L, Bamberg M, Rodemann HP (2000) TGF-beta1-mediated alterations of rat lung fibroblast differentiation resulting in the radiation-induced fibrotic phenotype. Int J Radiat Biol 76:503–509CrossRefPubMedGoogle Scholar
  26. Hall EJGA, Giaccia AJ (2006) Radiobiology for the radiologist, 6th edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  27. Helleday T, Lo J, van Gent DC, Engelward BP (2007) DNA double-strand break repair: from mechanistic understanding to cancer treatment. DNA Repair (Amst) 6:923–935CrossRefGoogle Scholar
  28. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8:193–204CrossRefPubMedGoogle Scholar
  29. Hendry JH, Thames HD (1986) The tissue-rescuing unit. Br J Radiol 59:628–630CrossRefPubMedGoogle Scholar
  30. Herfarth KK, Hof H, Bahner ML, Lohr F, Hoss A, van Kaick G, Wannenmacher M, Debus J (2003) Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. Int J Radiat Oncol Biol Phys 57:444–451CrossRefPubMedGoogle Scholar
  31. Herfarth KK, Debus J, Wannenmacher M (2004) Stereotactic radiation therapy of liver metastases: update of the initial phase-I/II trial. Front Radiat Ther Oncol 38:100–105CrossRefPubMedGoogle Scholar
  32. Hof H, Muenter M, Oetzel D, Hoess A, Debus J, Herfarth K (2007) Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC). Cancer 110:148–155CrossRefPubMedGoogle Scholar
  33. Jung H, Beck-Bornholdt HP, Svoboda V, Alberti W, Herrmann T (2001) Quantification of late complications after radiation therapy. Radiother Oncol 61:233–246CrossRefPubMedGoogle Scholar
  34. Kavanagh BD, Miften M, Rabinovitch RA (2011) Advances in treatment techniques: stereotactic body radiation therapy and the spread of hypofractionation. Cancer J 17:177–181CrossRefPubMedGoogle Scholar
  35. Kleinerman RA, Boice JD Jr, Storm HH, Sparen P, Andersen A, Pukkala E, Lynch CF, Hankey BF, Flannery JT (1995) Second primary cancer after treatment for cervical cancer. An international cancer registries study. Cancer 76:442–452CrossRefPubMedGoogle Scholar
  36. Mahaney BL, Meek K, Lees-Miller SP (2009) Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J 417:639–650PubMedCentralCrossRefPubMedGoogle Scholar
  37. Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, Bentzen SM, Nam J, Deasy JO (2010) Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 76:S10–S19PubMedCentralCrossRefPubMedGoogle Scholar
  38. Michalowski A (1981) Effects of radiation on normal tissues: hypothetical mechanisms and limitations of in situ assays of clonogenicity. Radiat Environ Biophys 19:157–172CrossRefPubMedGoogle Scholar
  39. Neglia JP, Friedman DL, Yasui Y, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL (2001) Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst 93:618–629CrossRefPubMedGoogle Scholar
  40. Paulus U, Potten CS, Loeffler M (1992) A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation. Cell Prolif 25:559–578CrossRefPubMedGoogle Scholar
  41. Paumier A, Le Pechoux C, Beaudre A, Negretti L, Ferreira I, Roberti E, Brahim J, Lefkopoulos D, Daly-Schweitzer N, Bourhis J, Bonvalot S (2011) IMRT or conformal radiotherapy for adjuvant treatment of retroperitoneal sarcoma? Radiother Oncol 99:73–78CrossRefPubMedGoogle Scholar
  42. Pedersen D, Bentzen SM, Overgaard J (1994) Early and late radiotherapeutic morbidity in 442 consecutive patients with locally advanced carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 29:941–952CrossRefPubMedGoogle Scholar
  43. Perks JR, Lehmann J, Chen AM, Yang CC, Stern RL, Purdy JA (2008) Comparison of peripheral dose from image-guided radiation therapy (IGRT) using kV cone beam CT to intensity-modulated radiation therapy (IMRT). Radiother Oncol 89:304–310CrossRefPubMedGoogle Scholar
  44. Purdy JA (2008) Dose to normal tissues outside the radiation therapy patient’s treated volume: a review of different radiation therapy techniques. Health Phys 95:666–676CrossRefPubMedGoogle Scholar
  45. Rodemann HP, Bamberg M (1995) Cellular basis of radiation-induced fibrosis. Radiother Oncol 35:83–90CrossRefPubMedGoogle Scholar
  46. Rubin P, Casarett GW (1968) Clinical radiation pathology as applied to curative radiotherapy. Cancer 22:767–778CrossRefPubMedGoogle Scholar
  47. Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein JN (1995) A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 33:99–109CrossRefPubMedGoogle Scholar
  48. Schultz-Hector S (1992) Radiation-induced heart disease: review of experimental data on dose response and pathogenesis. Int J Radiat Biol 61:149–160CrossRefPubMedGoogle Scholar
  49. Sterzing F, Stoiber EM, Nill S, Bauer H, Huber P, Debus J, Munter MW (2009) Intensity modulated radiotherapy (IMRT) in the treatment of children and adolescents–a single institution’s experience and a review of the literature. Radiat Oncol 4:37PubMedCentralCrossRefPubMedGoogle Scholar
  50. Sterzing F, Engenhart-Cabillic R, Flentje M, Debus J (2011) Image-guided radiotherapy: a new dimension in radiation oncology. Dtsch Arztebl Int 108:274–280PubMedCentralPubMedGoogle Scholar
  51. Swerdlow AJ, Barber JA, Hudson GV, Cunningham D, Gupta RK, Hancock BW, Horwich A, Lister TA, Linch DC (2000) Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 18:498–509PubMedGoogle Scholar
  52. Terezakis SA, Heron DE, Lavigne RF, Diehn M, Loo BW Jr (2011) What the diagnostic radiologist needs to know about radiation oncology. Radiology 261:30–44CrossRefPubMedGoogle Scholar
  53. Thames HD Jr, Withers HR, Peters LJ, Fletcher GH (1982) Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int J Radiat Oncol Biol Phys 8:219–226CrossRefPubMedGoogle Scholar
  54. Travis LB, Curtis RE, Storm H, Hall P, Holowaty E, Van Leeuwen FE, Kohler BA, Pukkala E, Lynch CF, Andersson M, Bergfeldt K, Clarke EA, Wiklund T, Stoter G, Gospodarowicz M, Sturgeon J, Fraumeni JF Jr, Boice JD Jr (1997) Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst 89:1429–1439CrossRefPubMedGoogle Scholar
  55. Travis LB, Allan IL, van Leewen FE (2008) Second cancers. In: de Vita VTJ, Lawrence TS, Rosenberg SA (eds) Cancer. Principles & practice of oncology, 8th edn. Kluwer/Lippincott William & Wilkins, Philadelphia, pp 2718–2743Google Scholar
  56. Trott KR (2009) Chapter 25. Second cancers after radiotherapy. In: Joiner M, Van der Kogel A (eds) Basic clinical radiobiology, 4th edn. Hodder Arnold, London, pp 339–352CrossRefGoogle Scholar
  57. Turesson I (1990) Individual variation and dose dependency in the progression rate of skin telangiectasia. Int J Radiat Oncol Biol Phys 19:1569–1574CrossRefPubMedGoogle Scholar
  58. Wolden SL, Lamborn KR, Cleary SF, Tate DJ, Donaldson SS (1998) Second cancers following pediatric Hodgkin’s disease. J Clin Oncol 16:536–544PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Radiooncology and Radiation TherapyHeidelberg University HospitalHeidelbergGermany

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