Reduced Normal Tissue Doses Through Advanced Technology

  • Matthias Guckenberger
  • Reinhart A. Sweeney
Part of the Medical Radiology book series (MEDRAD)


Re-irradiation is probably the most challenging situation in radiotherapy because the radiation tolerance of the normal tissue is significantly reduced compared with the first treatment series. Results with traditional radiotherapy techniques have been disappointing because of the poor conformality of the dose distributions: radiation doses were either insufficiently low resulting in poor rates of tumor control or substantial toxicity was the consequence of high-dose re-irradiation. This chapter will focus on modern techniques of radiation treatment planning and delivery, which make improved sparing of the normal tissue possible. All techniques will be discussed in the context of re-irradiation and theoretical and clinical data supporting the use of these technologies will be presented. Palliative reirradiation to moderate doses might be feasible without using advanced technology. However, under many circumstances 2D or 3D conformal approaches can not fulfill the required normal tissue constraints. The present chapter discusses the advantages and challenges associated with more complex planning and delivery methods.


Target Volume Planning Target Volume Dose Distribution Clinical Target Volume Gross Tumor Volume 
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.


  1. Ang KK et al (2001) Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys 50(4):1013–1020PubMedCrossRefGoogle Scholar
  2. Barker JL Jr et al (2004) Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system. Int J Radiat Oncol Biol Phys 59(4):960–970PubMedCrossRefGoogle Scholar
  3. Biagioli MC et al (2007) Intensity-modulated radiotherapy with concurrent chemotherapy for previously irradiated, recurrent head and neck cancer. Int J Radiat Oncol Biol Phys 69(4):1067–1073PubMedCrossRefGoogle Scholar
  4. Bortfeld T, Webb S (2009) Single-Arc IMRT? Phys Med Biol 54(1):N9–N20PubMedCrossRefGoogle Scholar
  5. Brandner ED et al (2006) Abdominal organ motion measured using 4D CT. Int J Radiat Oncol Biol Phys 65(2):554–560PubMedCrossRefGoogle Scholar
  6. Brock KK (2010) Results of a multi-institution deformable registration accuracy study (MIDRAS). Int J Radiat Oncol Biol Phys 76(2):583–596PubMedCrossRefGoogle Scholar
  7. Bzdusek K et al (2009) Development and evaluation of an efficient approach to volumetric arc therapy planning. Med Phys 36(6):2328–2339PubMedCrossRefGoogle Scholar
  8. Combs SE et al (2008) Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas. J Neurooncol 89(2):205–210PubMedCrossRefGoogle Scholar
  9. Dearnaley DP et al (1999) Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet 353(9149):267–272PubMedCrossRefGoogle Scholar
  10. Deodato F et al (2009) Stereotactic radiotherapy in recurrent gynecological cancer: a case series. Oncol Rep 22(2):415–419PubMedGoogle Scholar
  11. Duprez F et al (2009) Intensity-modulated radiotherapy for recurrent and second primary head and neck cancer in previously irradiated territory. Radiother Oncol 93(3):563–569PubMedCrossRefGoogle Scholar
  12. Engelsman M et al (2005) How much margin reduction is possible through gating or breath hold? Phys Med Biol 50(3):477–490PubMedCrossRefGoogle Scholar
  13. Even-Sapir E et al (2004) Detection of recurrence in patients with rectal cancer: PET/CT after abdominoperineal or anterior resection. Radiology 232(3):815–822PubMedCrossRefGoogle Scholar
  14. Fiorino C et al (2008) Evidence of limited motion of the prostate by carefully emptying the rectum as assessed by daily MVCT image guidance with helical tomotherapy. Int J Radiat Oncol Biol Phys 71(2):611–617PubMedCrossRefGoogle Scholar
  15. Fogliata A et al (2005) IMRT for breast. a planning study. Radiother Oncol 76(3):300–310PubMedCrossRefGoogle Scholar
  16. Fogliata A et al (2007) On the performances of different IMRT Treatment Planning Systems for selected paediatric cases. Radiat Oncol 2:7PubMedCrossRefGoogle Scholar
  17. Fuss M et al (2004) Repositioning accuracy of a commercially available double-vacuum whole body immobilization system for stereotactic body radiation therapy. Technol Cancer Res Treat 3(1):59–67PubMedGoogle Scholar
  18. Goitein M (2010) Trials and tribulations in charged particle radiotherapy. Radiother Oncol 95(1):23–31PubMedCrossRefGoogle Scholar
  19. Grosu AL et al (2005) Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys 63(2):511–519PubMedCrossRefGoogle Scholar
  20. Guckenberger M et al (2006) Cone-beam CT based image-guidance for extracranial stereotactic radiotherapy of intrapulmonary tumors. Acta Oncol 45(7):897–906PubMedCrossRefGoogle Scholar
  21. Guckenberger M et al (2007a) Precision required for dose-escalated treatment of spinal metastases and implications for image-guided radiation therapy (IGRT). Radiother Oncol 84(1):56–63PubMedCrossRefGoogle Scholar
  22. Guckenberger M et al (2007b) Reliability of the bony anatomy in image-guided stereotactic radiotherapy of brain metastases. Int J Radiat Oncol Biol Phys 69(1):294–301PubMedCrossRefGoogle Scholar
  23. Guckenberger M et al (2009a) Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes? Radiother Oncol 93(2):259–265PubMedCrossRefGoogle Scholar
  24. Guckenberger M et al (2009b) Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy. Radiother Oncol 91(3):288–295PubMedCrossRefGoogle Scholar
  25. Guckenberger M et al (2010) Stereotactic body radiotherapy for local boost irradiation in unfavourable locally recurrent gynaecological cancer. Radiother Oncol 94(1):53–59PubMedCrossRefGoogle Scholar
  26. Gutin PH et al (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 75(1):156–163PubMedCrossRefGoogle Scholar
  27. Hashimoto T et al (2006) Repeated proton beam therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 65(1):196–202PubMedCrossRefGoogle Scholar
  28. Hatakeyama T et al (2008) 11C-methionine (MET) and 18F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma. Eur J Nucl Med Mol Imaging 35(11):2009–2017PubMedCrossRefGoogle Scholar
  29. Heron DE et al (2009) Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Int J Radiat Oncol Biol Phys 75(5):1493–1500PubMedCrossRefGoogle Scholar
  30. Hurkmans CW et al (2001) Set-up verification using portal imaging; review of current clinical practice. Radiother Oncol 58(2):105–120PubMedCrossRefGoogle Scholar
  31. ICRU (1993) International commission on radiation units and measurements: prescribing, recording and reporting photon beam therapy, report 50. ICRU, BethesdaGoogle Scholar
  32. ICRU (1999) International commission on radiation units and measurements: prescribing, recording and reporting photon beam therapy, report 62. ICRU, BethesdaGoogle Scholar
  33. Ito K et al (1992) Recurrent rectal cancer and scar: differentiation with PET and MR imaging. Radiology 182(2):549–552PubMedGoogle Scholar
  34. Jingu K et al (2010) Focal dose escalation using FDG-PET-guided intensity-modulated radiation therapy boost for postoperative local recurrent rectal cancer: a planning study with comparison of DVH and NTCP. BMC Cancer 10:127PubMedCrossRefGoogle Scholar
  35. Keall PJ et al (2006) Geometric accuracy of a real-time target tracking system with dynamic multileaf collimator tracking system. Int J Radiat Oncol Biol Phys 65(5):1579–1584PubMedCrossRefGoogle Scholar
  36. Kelly P et al (2010) Stereotactic body radiation therapy for patients with lung cancer previously treated with thoracic radiation. Int J Radiat Oncol Biol Phys (Epub ahead of print)Google Scholar
  37. Korreman SS, Juhler-Nottrup T, Boyer AL (2008) Respiratory gated beam delivery cannot facilitate margin reduction, unless combined with respiratory correlated image guidance. Radiother Oncol 86(1):61–68PubMedCrossRefGoogle Scholar
  38. Kupelian PA et al (2005) Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: observations on tumor regression during treatment. Int J Radiat Oncol Biol Phys 63(4):1024–1028PubMedCrossRefGoogle Scholar
  39. Lax I et al (1994) Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol 33(6):677–683PubMedCrossRefGoogle Scholar
  40. Lebesque JV, Keus RB (1991) The simultaneous boost technique: the concept of relative normalized total dose. Radiother Oncol 22(1):45–55PubMedCrossRefGoogle Scholar
  41. Lee JK et al (1981) CT appearance of the pelvis after abdomino-perineal resection for rectal carcinoma. Radiology 141(3):737–741PubMedGoogle Scholar
  42. Lee N et al (2007) Salvage re-irradiation for recurrent head and neck cancer. Int J Radiat Oncol Biol Phys 68(3):731–740PubMedCrossRefGoogle Scholar
  43. Lee IH et al (2009) Association of 11C-methionine PET uptake with site of failure after concurrent temozolomide and radiation for primary glioblastoma multiforme. Int J Radiat Oncol Biol Phys 73(2):479–485PubMedCrossRefGoogle Scholar
  44. Leksell L (1951) The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 102(4):316–319PubMedGoogle Scholar
  45. Leksell L (1968) Cerebral radiosurgery. I. Gammathalanotomy in two cases of intractable pain. Acta Chir Scand 134(8):585–595PubMedGoogle Scholar
  46. Lin R et al (1999) Nasopharyngeal carcinoma: repeat treatment with conformal proton therapy–dose-volume histogram analysis. Radiology 213(2):489–494PubMedGoogle Scholar
  47. Maciejewski B, Taylor JM, Withers HR (1986) Alpha/beta value and the importance of size of dose per fraction for late complications in the supraglottic larynx. Radiother Oncol 7(4):323–326PubMedCrossRefGoogle Scholar
  48. Mackie TR et al (1993) Tomotherapy: a new concept for the delivery of dynamic conformal radiotherapy. Med Phys 20(6):1709–1719PubMedCrossRefGoogle Scholar
  49. Mahan SL et al (2005) Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis. Int J Radiat Oncol Biol Phys 63(5):1576–1583PubMedCrossRefGoogle Scholar
  50. Marks LB, Ten Haken RK, Martel MK (2010) Guest editor’s introduction to QUANTEC: a users guide. Int J Radiat Oncol Biol Phys 76(3 Suppl):S1–S2PubMedCrossRefGoogle Scholar
  51. Marucci L et al (2006) Conservation treatment of the eye: conformal proton reirradiation for recurrent uveal melanoma. Int J Radiat Oncol Biol Phys 64(4):1018–1022PubMedCrossRefGoogle Scholar
  52. Mayr NA et al (2006) Serial therapy-induced changes in tumor shape in cervical cancer and their impact on assessing tumor volume and treatment response. AJR Am J Roentgenol 187(1):65–72PubMedCrossRefGoogle Scholar
  53. Milker-Zabel S et al (2003) Clinical results of retreatment of vertebral bone metastases by stereotactic conformal radiotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 55(1):162–167PubMedCrossRefGoogle Scholar
  54. Nevinny-Stickel M, Sweeney RA, Bale RJ, Posch A, Auberger T, Lukas P. (2004) Reproducibility of patient positioning for fractionated extracranial stereotactic radiotherapy using a double-vacuum technique. Strahlenther Onkol 180(2):117–122PubMedCrossRefGoogle Scholar
  55. Nieder C et al (2006) Update of human spinal cord reirradiation tolerance based on additional data from 38 patients. Int J Radiat Oncol Biol Phys 66(5):1446–1449PubMedCrossRefGoogle Scholar
  56. Otto K (2008) Volumetric modulated arc therapy: IMRT in a single gantry arc. Med Phys 35(1):310–317PubMedCrossRefGoogle Scholar
  57. Pauleit D et al (2005) O-(2-[18F]fluoroethyl)-l-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain 128(Pt 3):678–687PubMedCrossRefGoogle Scholar
  58. Polat B et al (2008) Intra-fractional uncertainties in image-guided intensity-modulated radiotherapy (IMRT) of prostate cancer. Strahlenther Onkol 184(12):668–673PubMedCrossRefGoogle Scholar
  59. Poltinnikov IM et al (2005) Combination of longitudinal and circumferential three-dimensional esophageal dose distribution predicts acute esophagitis in hypofractionated reirradiation of patients with non-small-cell lung cancer treated in stereotactic body frame. Int J Radiat Oncol Biol Phys 62(3):652–658PubMedCrossRefGoogle Scholar
  60. Popovtzer A et al (2009) The pattern of failure after reirradiation of recurrent squamous cell head and neck cancer: implications for defining the targets. Int J Radiat Oncol Biol Phys 74(5):1342–1347PubMedCrossRefGoogle Scholar
  61. Purdie TG et al (2007) Cone-beam computed tomography for on-line image guidance of lung stereotactic radiotherapy: localization, verification, and intrafraction tumor position. Int J Radiat Oncol Biol Phys 68(1):243–252PubMedCrossRefGoogle Scholar
  62. Ramakrishna N et al (2010) A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery system for intracranial lesions. Radiother Oncol 95(1):109–115PubMedCrossRefGoogle Scholar
  63. Rwigema JC, Heron DE, Ferris RL, Gibson M, Quinn A, Yang Y, Ozhasoglu C, Burton S (2010) Fractionated stereotactic body radiation therapy in the treatment of previously-irradiated recurrent head and neck carcinoma: updated report of the University of Pittsburgh experience. Am J Clin Oncol 33(3):286–293.PubMedGoogle Scholar
  64. Schwer AL et al (2008) A phase I dose-escalation study of fractionated stereotactic radiosurgery in combination with gefitinib in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 70(4):993–1001PubMedCrossRefGoogle Scholar
  65. Seppenwoolde Y et al (2002) Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy. Int J Radiat Oncol Biol Phys 53(4):822–834PubMedCrossRefGoogle Scholar
  66. Seppenwoolde Y et al (2007) Accuracy of tumor motion compensation algorithm from a robotic respiratory tracking system: a simulation study. Med Phys 34(7):2774–2784PubMedCrossRefGoogle Scholar
  67. Shepherd SF et al (1997) Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. Int J Radiat Oncol Biol Phys 37(2):393–398PubMedCrossRefGoogle Scholar
  68. Smitsmans MH et al (2008) The influence of a dietary protocol on cone beam CT-guided radiotherapy for prostate cancer patients. Int J Radiat Oncol Biol Phys 71(4):1279–1286PubMedCrossRefGoogle Scholar
  69. Sohn M, Weinmann M, Alber M (2009) Intensity-modulated radiotherapy optimization in a quasi-periodically deforming patient model. Int J Radiat Oncol Biol Phys 75(3):906–914PubMedCrossRefGoogle Scholar
  70. Sonke JJ et al (2005) Respiratory correlated cone beam CT. Med Phys 32(4):1176–1186PubMedCrossRefGoogle Scholar
  71. Sonke JJ et al (2009) Frameless stereotactic body radiotherapy for lung cancer using four-dimensional cone beam CT guidance. Int J Radiat Oncol Biol Phys 74(2):567–574PubMedCrossRefGoogle Scholar
  72. Sterzing F et al (2010) Spinal cord sparing reirradiation with helical tomotherapy. Cancer 116(16):3961–3968PubMedCrossRefGoogle Scholar
  73. Sykes JR et al (2005) A feasibility study for image guided radiotherapy using low dose, high speed, cone beam X-ray volumetric imaging. Radiother Oncol 77(1):45–52PubMedCrossRefGoogle Scholar
  74. Terakawa Y et al (2008) Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med 49(5):694–699PubMedCrossRefGoogle Scholar
  75. Underberg RW et al (2005) Benefit of respiration-gated stereotactic radiotherapy for stage I lung cancer: an analysis of 4DCT datasets. Int J Radiat Oncol Biol Phys 62(2):554–560PubMedCrossRefGoogle Scholar
  76. van Herk M (2004) Errors and margins in radiotherapy. Semin Radiat Oncol 14(1):52–64PubMedCrossRefGoogle Scholar
  77. Verellen D et al (2007) Innovations in image-guided radiotherapy. Nat Rev Cancer 7(12):949–960PubMedCrossRefGoogle Scholar
  78. Wachter S et al (2002) The influence of a rectal balloon tube as internal immobilization device on variations of volumes and dose-volume histograms during treatment course of conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 52(1):91–100PubMedCrossRefGoogle Scholar
  79. Wilbert J et al (2008) Tumor tracking and motion compensation with an adaptive tumor tracking system (ATTS): system description and prototype testing. Med Phys 35(19):3911–9921PubMedCrossRefGoogle Scholar
  80. Wolthaus JW et al (2008) Comparison of different strategies to use four-dimensional computed tomography in treatment planning for lung cancer patients. Int J Radiat Oncol Biol Phys 70(4):1229–1238PubMedCrossRefGoogle Scholar
  81. Yan D et al (1997) Adaptive radiation therapy. Phys Med Biol 42(1):123–132PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity Hospital WuerzburgWuerzburg Germany

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