Skip to main content
SpringerLink
Log in

Normalgewebe: Strahlenempfindlichkeit, Toxizität, Konsequenzen für die Planung

Normal tissue: radiosensitivity, toxicity, consequences for planning

  • Leitthema
  • Published:
Der Radiologe Aims and scope Submit manuscript

Zusammenfassung

Die Radiotherapie gehört zusammen mit der Chirurgie, Chemotherapie und neuerdings der Immuntherapie zu den elementaren Säulen der Krebstherapie. Zunehmend in den Fokus der modernen Krebstherapie rückt die Lebensqualität der Patienten, die in besonderem Maße von den akuten und späten Normalgewebsreaktionen nach der Tumortherapie abhängt. Aufgrund verbesserter Heilungsraten für Krebs in den vergangenen Jahrzehnten gewinnen dabei besonders die Spätreaktionen der Radiotherapie an Bedeutung. Ein tiefgreifendes Verständnis der radiogenen Normalgewebsreaktionen erlaubt eine suffiziente Diagnose und spezifische Therapie der Nebenwirkungen und damit eine Verbesserung der Lebensqualität der Patienten. In diesem Beitrag werden Normalgewebsreaktionen verschiedener Organsysteme unter Berücksichtigung der Strahlenbiologie behandelt sowie vorhandene und zukünftige Möglichkeiten zur Behandlung von Strahlennebenwirkungen diskutiert.

Abstract

Along with chemotherapy, surgery and immunotherapy, radiotherapy is a mainstay of cancer treatment. Considering the improving survival rates for various malignancies during the past decades, the importance of radiation-induced late normal tissue response is increasing. Quality of life is becoming an important issue in modern cancer treatment and is correlated with acute and late normal tissue response after radiotherapy. A profound understanding of radiation-induced normal tissue response is necessary to sufficiently diagnose and treat radiation-induced side effects and thereby increase the patients’ quality of life. Here, the various normal tissue responses in consideration of the radiation biology are specified and prospective options to attenuate radiation-induced side effects are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Welzel T, Tanner JM (2018) Nebenwirkungen nach Strahlentherapie in der Bildgebung. Radiologe 58. https://doi.org/10.1007/s00117-018-0412-6

    Article  PubMed  Google Scholar 

  2. Sterzing F et al (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 4:37

    Article  PubMed  PubMed Central  Google Scholar 

  3. Askoxylakis V et al (2016) Intensity modulated radiation therapy (IMRT) for sinonasal tumors: a single center long-term clinical analysis. Radiat Oncol 11:17

    Article  PubMed  PubMed Central  Google Scholar 

  4. Nutting CM et al (2011) Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 12(2):127–136

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hall EJ, Wuu C‑S (2003) Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 56(1):83–88

    Article  PubMed  Google Scholar 

  6. Zwicker F et al (2015) In vivo measurement of dose distribution in patients’ lymphocytes: helical tomotherapy versus step-and-shoot IMRT in prostate cancer. J Radiat Res 56(2):239–247

    Article  PubMed  CAS  Google Scholar 

  7. Nicolay NH et al (2016) High dose-rate endoluminal brachytherapy for primary and recurrent esophageal cancer: experience from a large single-center cohort. Strahlenther Onkol 192(7):458–466

    Article  PubMed  Google Scholar 

  8. Roeder F et al (2016) Intraoperative electron radiation therapy combined with external beam radiation therapy and limb sparing surgery in extremity soft tissue sarcoma: a retrospective single center analysis of 183 cases. Radiother Oncol 119(1):22–29

    Article  PubMed  Google Scholar 

  9. Hoffmann M et al (2015) Long term results of postoperative intensity-modulated radiation therapy (IMRT) in the treatment of squamous cell carcinoma (SCC) located in the oropharynx or oral cavity. Radiat Oncol 10:251

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Roeder F et al (2014) Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer. Radiat Oncol 9:191

    Article  PubMed  PubMed Central  Google Scholar 

  11. Thieke C et al (2015) Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy. Radiat Oncol 10(1):267

    Article  PubMed  PubMed Central  Google Scholar 

  12. Miralbell R et al (2002) Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int J Radiat Oncol Biol Phys 54(3):824–829

    Article  PubMed  Google Scholar 

  13. Durante M, Debus Heavy Charged Particles J (2018) Does improved precision and higher biological effectiveness translate to better outcome in patients? Semin Radiat Oncol 28(2):160–167

    Article  PubMed  Google Scholar 

  14. Jensen AD et al (2016) High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years’ experience with raster-scanned carbon ion therapy. Radiother Oncol 118(2):272–280

    Article  PubMed  Google Scholar 

  15. Jensen AD et al (2015) Combined intensity-modulated radiotherapy plus raster-scanned carbon ion boost for advanced adenoid cystic carcinoma of the head and neck results in superior locoregional control and overall survival. Cancer 121(17):3001–3009

    Article  PubMed  CAS  Google Scholar 

  16. Uhl M et al (2014) Highly effective treatment of skull base chordoma with carbon ion irradiation using a raster scan technique in 155 patients: first long-term results. Cancer 120(21):3410–3417

    Article  PubMed  CAS  Google Scholar 

  17. Huber PE et al (2001) Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed beam? Radiother Oncol 59(2):161–167

    Article  PubMed  CAS  Google Scholar 

  18. Emami B et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21(1):109–122

    Article  PubMed  CAS  Google Scholar 

  19. Lawrence YR et al (2010) Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys 76(3 Suppl):S20–S27

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wenz F et al (2000) Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI). Int J Radiat Oncol Biol Phys 48(5):1497–1501

    Article  PubMed  CAS  Google Scholar 

  21. Hempen C, Weiss E, Hess CF (2002) Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? Support Care Cancer 10(4):322–328

    Article  PubMed  Google Scholar 

  22. Kirkpatrick JP et al (2011) Estimating normal tissue toxicity in radiosurgery of the CNS: application and limitations of QUANTEC. J Radiosurg SBRT 1(2):95–107

    PubMed  PubMed Central  Google Scholar 

  23. Huber PE et al (2001) Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 49(5):1339–1349

    Article  PubMed  CAS  Google Scholar 

  24. Combs SE et al (2013) Skull base meningiomas: long-term results and patient self-reported outcome in 507 patients treated with fractionated stereotactic radiotherapy (FSRT) or intensity modulated radiotherapy (IMRT). Radiother Oncol 106(2):186–191

    Article  PubMed  Google Scholar 

  25. Combs SE et al (2005) Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys 63(1):75–81

    Article  PubMed  Google Scholar 

  26. Saleh-Ebrahimi L et al (2013) Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer—a retrospective single center analysis. Radiat Oncol 8:20

    Article  PubMed  PubMed Central  Google Scholar 

  27. Henson BS et al (2001) Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy. Oral Oncol 37(1):84–93

    Article  PubMed  CAS  Google Scholar 

  28. Stephens LC et al (1991) Radiation apoptosis of serous acinar cells of salivary and lacrimal glands. Cancer 67(6):1539–1543

    Article  PubMed  CAS  Google Scholar 

  29. Wang X, Eisbruch A (2016) IMRT for head and neck cancer: reducing xerostomia and dysphagia. J Radiat Res 57(Suppl 1):i69–i75

    Article  PubMed  PubMed Central  Google Scholar 

  30. Munter MW et al (2007) Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine. Int J Radiat Oncol Biol Phys 67(3):651–659

    Article  PubMed  Google Scholar 

  31. Bras J, de Jonge HKT, van Merkesteyn JPR (1990) Osteoradionecrosis of the mandible: pathogenesis. Am J Otolaryngol 11(4):244–250

    Article  PubMed  CAS  Google Scholar 

  32. Zwicker F et al (2011) Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer. Head Neck 33(12):1695–1702

    Article  PubMed  Google Scholar 

  33. Coggle JE, Lambert BE, Moores SR (1986) Radiation effects in the lung. Environ Health Perspect 70:261–291

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Roeder F et al (2010) Correlation of patient-related factors and dose-volume histogram parameters with the onset of radiation pneumonitis in patients with small cell lung cancer. Strahlenther Onkol 186(3):149–156

    Article  PubMed  Google Scholar 

  35. Guckenberger M et al (2013) Safety and efficacy of stereotactic body radiotherapy for stage I non-small-cell lung cancer in routine clinical practice: a patterns-of-care and outcome analysis. J Thorac Oncol 8(8):1050–1058

    Article  PubMed  CAS  Google Scholar 

  36. Catane R et al (1979) Pulmonary toxicity after radiation and bleomycin: a review. Int J Radiat Oncol Biol Phys 5(9):1513–1518

    Article  PubMed  CAS  Google Scholar 

  37. Pearson D et al (1978) The interaction of actinomycin D and radiation. Int J Radiat Oncol Biol Phys 4(1):71–73

    Article  PubMed  CAS  Google Scholar 

  38. Cuzick J et al (1987) Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer. Cancer Treat Rep 71(1):15–29

    PubMed  CAS  Google Scholar 

  39. Weberpals J et al (2018) Long-term heart-specific mortality among 347 476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort study. Eur Heart J. https://doi.org/10.1093/eurheartj/ehy167

    Article  PubMed  Google Scholar 

  40. Schultz-Hector S, Trott K‑R (2007) Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data? Int J Radiat Oncol Biol Phys 67(1):10–18

    Article  PubMed  CAS  Google Scholar 

  41. Halyard MY et al (2009) Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. J Clin Oncol 27(16):2638

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Classen J et al (1998) Radiation-induced gastrointestinal toxicity. Pathophysiology, approaches to treatment and prophylaxis. Strahlenther Onkol 174:82–84

    Article  PubMed  Google Scholar 

  43. Dawson LA et al (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53(4):810–821

    Article  PubMed  Google Scholar 

  44. Russell AH et al (1993) Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the rtog dose escalating protocol. Int J Radiat Oncol Biol Phys 27(1):117–123

    Article  PubMed  CAS  Google Scholar 

  45. Andratschke N et al (2018) The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases. BMC Cancer 18(1):283

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Pan CC et al (2010) Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 76(3):S94–S100

    Article  PubMed  PubMed Central  Google Scholar 

  47. Dawson LA et al (2010) Radiation-associated kidney injury. Int J Radiat Oncol Biol Phys 76(3, Supplement):S108–S115

    Article  PubMed  Google Scholar 

  48. Cheng JC, Schultheiss TE, Wong JY (2008) Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation. Int J Radiat Oncol Biol Phys 71(5):1436–1443

    Article  PubMed  CAS  Google Scholar 

  49. Crew JP, Jephcott CR, Reynard JM (2001) Radiation-induced haemorrhagic cystitis. Eur Urol 40(2):111–123

    Article  PubMed  CAS  Google Scholar 

  50. Nicolay NH et al (2015) Mesenchymal stem cells—a new hope for radiotherapy-induced tissue damage? Cancer Lett 366(2):133–140

    Article  PubMed  CAS  Google Scholar 

  51. Nicolay NH et al (2015) Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic. Oncotarget 6(23):19366–19380

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lalu MM et al (2012) Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS ONE 7(10):e47559

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Chapel A et al (2013) New insights for pelvic radiation disease treatment: multipotent stromal cell is a promise mainstay treatment for the restoration of abdominopelvic severe chronic damages induced by radiotherapy. World J Stem Cells 5(4):106–111

    Article  PubMed  PubMed Central  Google Scholar 

  54. Rühle A et al (2018) The radiation resistance of human multipotent mesenchymal stromal cells is independent of their tissue of origin. Int J Radiat Oncol Biol Phys 100(5):1259–1269

    Article  PubMed  Google Scholar 

  55. Nicolay NH et al (2013) Mesenchymal stem cells retain their defining stem cell characteristics after exposure to ionizing radiation. Int J Radiat Oncol Biol Phys 87(5):1171–1178

    Article  PubMed  CAS  Google Scholar 

  56. Abdollahi A et al (2005) Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med 201(6):925–935

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Flechsig P et al (2012) LY2109761 attenuates radiation-induced pulmonary murine fibrosis via reversal of TGF-beta and BMP-associated proinflammatory and proangiogenic signals. Clin Cancer Res 18(13):3616–3627

    Article  PubMed  CAS  Google Scholar 

  58. Dadrich M et al (2016) Combined inhibition of TGFbeta and PDGF signaling attenuates radiation-induced pulmonary fibrosis. Oncoimmunology 5(5):e1123366

    Article  PubMed  Google Scholar 

  59. Bickelhaupt S et al (2017) Effects of CTGF blockade on attenuation and reversal of radiation-induced pulmonary fibrosis. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djw339

    Article  PubMed  Google Scholar 

  60. Gorina E et al (2017) PRAISE, a randomized, placebo-controlled, double-blind phase 2 clinical trial of pamrevlumab (FG-3019) in IPF patients. Eur Respiratory Soc 50:OA3400. https://doi.org/10.1183/1393003.congress-2017.OA3400

    Article  Google Scholar 

  61. Sternlicht MD et al (2018) Radiation-induced pulmonary gene expression changes are attenuated by the CTGF antibody Pamrevlumab. Respir Res 19(1):14

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für RadioOnkologie und Strahlentherapie, Universitätsklinik Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland

    A. Rühle &  P. E. Huber

  2. KKE Molekulare und RadioOnkologie, Deutsches Krebsforschungszentrum (dkfz), Im Neuenheimer Feld 280, 69120, Heidelberg, Deutschland

    A. Rühle &  P. E. Huber

Authors
  1. A. Rühle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. E. Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. E. Huber.

Ethics declarations

Interessenkonflikt

A. Rühle und P. E. Huber geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rühle, A., Huber, P.E. Normalgewebe: Strahlenempfindlichkeit, Toxizität, Konsequenzen für die Planung. Radiologe 58, 746–753 (2018). https://doi.org/10.1007/s00117-018-0430-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00117-018-0430-4

Schlüsselwörter

Keywords

Search

Navigation