Seminars in Radiation Oncology
Volume 17, Issue 2 , Pages 131-140 , April 2007

Normal Tissue Tolerance Dose Metrics for Radiation Therapy of Major Organs

  • Michael T. Milano, MD, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Michael T. Milano, MD, PhD, Department of Radiation Oncology and James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 647, Rochester, NY 14642.
    • ,
  • Louis S. Constine, MD
    • ,
  • Paul Okunieff, MD

References 

  1. Rubin P, Casarett G. Clinical Radiation Pathology. Philadelphia: Saunders; 1968;
  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. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31:1341–1346
  4. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–181
  5. Marcus RB, Million RR. The incidence of myelitis after irradiation of the cervical spinal cord. Int J Radiat Oncol Biol Phys. 1990;19:3–8
  6. Marucci L, Niemierko A, Liebsch NJ, 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. 2004;59:551–555
  7. Merchant TE, Kiehna EN, Li C, et al. Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma. Int J Radiat Oncol Biol Phys. 2006;65:210–221
  8. Armstrong CL, Hunter JV, Ledakis GE, et al. Late cognitive and radiographic changes related to radiotherapy: Initial prospective findings. Neurology. 2002;59:40–48
  9. Brown PD, Buckner JC, O’Fallon JR, et al. Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the folstein mini-mental state examination. J Clin Oncol. 2003;21:2519–2524
  10. Laack NN, Brown PD, Ivnik RJ, et al. Cognitive function after radiotherapy for supratentorial low-grade glioma: A North Central Cancer Treatment Group prospective study. Int J Radiat Oncol Biol Phys. 2005;63:1175–1183
  11. Torres IJ, Mundt AJ, Sweeney PJ, et al. A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology. 2003;60:1113–1118
  12. Vigliani MC, Sichez N, Poisson M, et al. A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results. Int J Radiat Oncol Biol Phys. 1996;35:527–533
  13. Chin LS, Ma L, DiBiase S. Radiation necrosis following gamma knife surgery: A case-controlled comparison of treatment parameters and long-term clinical follow up. J Neurosurg. 2001;94:899–904
  14. Flickinger JC, Lunsford LD, Kondziolka D. Dose-volume considerations in radiosurgery. Stereotact Funct Neurosurg. 1991;57:99–105
  15. Flickinger JC, Lunsford LD, Wu A, et al. Predicted dose-volume isoeffect curves for stereotactic radiosurgery with the 60Co gamma unit. Acta Oncol. 1991;30:363–367
  16. Levegrun S, Hof H, Essig M, et al. Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: Correlation with dose distribution parameters. Int J Radiat Oncol Biol Phys. 2004;59:796–808
  17. Liu Y, Xiao S, Liu M, et al. Analysis of related factors in complications of stereotactic radiosurgery in intracranial tumors. Stereotact Funct Neurosurg. 2000;75:129–132
  18. Valery CA, Cornu P, Noel G, et al. Predictive factors of radiation necrosis after radiosurgery for cerebral metastases. Stereotact Funct Neurosurg. 2003;81:115–119
  19. Debus J, Hug EB, Liebsch NJ, et al. Brainstem tolerance to conformal radiotherapy of skull base tumors. Int J Radiat Oncol Biol Phys. 1997;39:967–975
  20. Debus J, Hug EB, Liebsch NJ, et al. Dose-volume tolerance of the brainstem after high-dose radiotherapy. Front Radiat Ther Oncol. 1999;33:305–314
  21. Eisbruch A, Kim HM, Terrell JE, et al. Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001;50:695–704
  22. Eisbruch A, Ship JA, Dawson LA, et al. Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer. World J Surg. 2003;27:832–837
  23. Eisbruch A, Ten Haken RK, Kim HM, et al. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys. 1999;45:577–587
  24. Chao KS. Protection of salivary function by intensity-modulated radiation therapy in patients with head and neck cancer. Semin Radiat Oncol. 2002;12:20–25
  25. Chao KS, Deasy JO, Markman J, et al. A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: Initial results. Int J Radiat Oncol Biol Phys. 2001;49:907–916
  26. Blanco AI, Chao KS, El Naqa I, et al. Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:1055–1069
  27. Amosson CM, Teh BS, Van TJ, et al. Dosimetric predictors of xerostomia for head-and-neck cancer patients treated with the smart (simultaneous modulated accelerated radiation therapy) boost technique. Int J Radiat Oncol Biol Phys. 2003;56:136–144
  28. Maes A, Weltens C, Flamen P, et al. Preservation of parotid function with uncomplicated conformal radiotherapy. Radiother Oncol. 2002;63:203–211
  29. Munter MW, Karger CP, Hoffner SG, et al. Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys. 2004;58:175–184
  30. Pacholke HD, Amdur RJ, Morris CG, et al. Late xerostomia after intensity-modulated radiation therapy versus conventional radiotherapy. Am J Clin Oncol. 2005;28:351–358
  31. Roesink JM, Schipper M, Busschers W, et al. A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: implications for future trials. Int J Radiat Oncol Biol Phys. 2005;63:1006–1009
  32. Bussels B, Maes A, Flamen P, et al. Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer. Radiother Oncol. 2004;73:297–306
  33. Braam PM, Roesink JM, Moerland MA, et al. Long-term parotid gland function after radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:659–664
  34. Roesink JM, Moerland MA, Battermann JJ, et al. Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region. Int J Radiat Oncol Biol Phys. 2001;51:938–946
  35. Jellema AP, Doornaert P, Slotman BJ, et al. Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy?. Radiother Oncol. 2005;77:164–171
  36. McDonald S, Meyerowitz C, Smudzin T, et al. Preliminary results of a pilot study using WR-2721 before fractionated irradiation of the head and neck to reduce salivary gland dysfunction. Int J Radiat Oncol Biol Phys. 1994;29:747–754
  37. Konings AW, Cotteleer F, Faber H, et al. Volume effects and region-dependent radiosensitivity of the parotid gland. Int J Radiat Oncol Biol Phys. 2005;62:1090–1095
  38. Fisher J, Scott C, Scarantino CW, et al. Phase III quality-of-life study results: Impact on patients’ quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer—RTOG 97-09. Int J Radiat Oncol Biol Phys. 2003;56:832–836
  39. Woynarowska B, Roberts K, Herman TS, et al. Pilocarpine, a salivary gland radioprotectant, does not inhibit cytotoxic effect of gamma-radiation on squamous cell carcinoma in vitro. Int J Radiat Oncol Biol Phys. 1997;39:751–755
  40. Seppenwoolde Y, Lebesque JV, de Jaeger K, et al. Comparing different NTCP models that predict the incidence of radiation pneumonitis (Normal tissue complication probability). Int J Radiat Oncol Biol Phys. 2003;55:724–735
  41. Kwa SL, Lebesque JV, Theuws JC, et al. Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys. 1998;42:1–9
  42. Armstrong J, Raben A, Zelefsky M, et al. Promising survival with three-dimensional conformal radiation therapy for non-small cell lung cancer. Radiother Oncol. 1997;44:17–22
  43. Yorke ED, Jackson A, Rosenzweig KE, et al. Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study. Int J Radiat Oncol Biol Phys. 2005;63:672–682
  44. Yorke ED, Jackson A, Rosenzweig KE, et al. Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys. 2002;54:329–339
  45. Graham MV, Purdy JA, Emami B, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys. 1999;45:323–329
  46. Hernando ML, Marks LB, Bentel GC, et al. Radiation-induced pulmonary toxicity: A dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys. 2001;51:650–659
  47. Tsujino K, Hirota S, Endo M, et al. Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys. 2003;55:110–115
  48. Bradley J, Graham MV, Winter K, et al. Toxicity and outcome results of RTOG 9311: A phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys. 2005;61:318–328
  49. Hayman JA, Martel MK, Ten Haken RK, et al. Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: Update of a phase I trial. J Clin Oncol. 2001;19:127–136
  50. Narayan S, Henning GT, Ten Haken RK, et al. Results following treatment to doses of 92.4 or 102.9 Gy on a phase I dose escalation study for non-small cell lung cancer. Lung Cancer. 2004;44:79–88
  51. Rosenzweig KE, Mychalczak B, Fuks Z, et al. Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer. Cancer J. 2000;6:82–87
  52. Marks LB, Hollis D, Munley M, et al. The role of lung perfusion imaging in predicting the direction of radiation-induced changes in pulmonary function tests. Cancer. 2000;88:2135–2141
  53. 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
  54. Allen AM, Henning GT, Ten Haken RK, et al. Do dose-volume metrics predict pulmonary function changes in lung irradiation?. Int J Radiat Oncol Biol Phys. 2003;55:921–929
  55. Fan M, Marks LB, Hollis D, et al. Can we predict radiation-induced changes in pulmonary function based on the sum of predicted regional dysfunction?. J Clin Oncol. 2001;19:543–550
  56. Fan M, Marks LB, Lind P, et al. Relating radiation-induced regional lung injury to changes in pulmonary function tests. Int J Radiat Oncol Biol Phys. 2001;51:311–317
  57. 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
  58. Garipagaoglu M, Munley MT, Hollis D, et al. The effect of patient-specific factors on radiation-induced regional lung injury. Int J Radiat Oncol Biol Phys. 1999;45:331–338
  59. 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
  60. Chen Y, Williams J, Ding I, et al. Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol. 2002;12:26–33
  61. 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
  62. Gagliardi G, Lax I, Rutqvist LE. Partial irradiation of the heart. Semin Radiat Oncol. 2001;11:224–233
  63. Adams MJ, Hardenbergh PH, Constine LS, et al. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol. 2003;45:55–75
  64. Gagliardi G, Lax I, Ottolenghi A, et al. Long-term cardiac mortality after radiotherapy of breast cancer—Application of the relative seriality model. Br J Radiol. 1996;69:839–846
  65. Eriksson F, Gagliardi G, Liedberg A, et al. Long-term cardiac mortality following radiation therapy for Hodgkin’s disease: Analysis with the relative seriality model. Radiother Oncol. 2000;55:153–162
  66. Singh AK, Lockett MA, Bradley JD. Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2003;55:337–341
  67. Maguire PD, Sibley GS, Zhou SM, et al. Clinical and dosimetric predictors of radiation-induced esophageal toxicity. Int J Radiat Oncol Biol Phys. 1999;45:97–103
  68. Ahn SJ, Kahn D, Zhou S, et al. Dosimetric and clinical predictors for radiation-induced esophageal injury. Int J Radiat Oncol Biol Phys. 2005;61:335–347
  69. Eifel PJ, Levenback C, Wharton JT, et al. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys. 1995;32:1289–1300
  70. Lee WR, Hanks GE, Hanlon AL, et al. Lateral rectal shielding reduces late rectal morbidity following high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: Further evidence for a significant dose effect. Int J Radiat Oncol Biol Phys. 1996;35:251–257
  71. Perez CA, Grigsby PW, Lockett MA, et al. Radiation therapy morbidity in carcinoma of the uterine cervix: Dosimetric and clinical correlation. Int J Radiat Oncol Biol Phys. 1999;44:855–866
  72. Roeske JC, Mundt AJ, Halpern H, et al. Late rectal sequelae following definitive radiation therapy for carcinoma of the uterine cervix: A dosimetric analysis. Int J Radiat Oncol Biol Phys. 1997;37:351–358
  73. Schultheiss TE, Lee WR, Hunt MA, et al. Late GI and GU complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys. 1997;37:3–11
  74. Fiorino C, Sanguineti G, Cozzarini C, et al. Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer. Int J Radiat Oncol Biol Phys. 2003;57:953–962
  75. Huang EH, Pollack A, Levy L, et al. Late rectal toxicity: Dose-volume effects of conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2002;54:1314–1321
  76. Jackson A, Skwarchuk MW, Zelefsky MJ, et al. Late rectal bleeding after conformal radiotherapy of prostate cancer (II. Volume effects and dose-volume histograms). Int J Radiat Oncol Biol Phys. 2001;49:685–698
  77. Kupelian PA, Reddy CA, Carlson TP, et al. Dose/volume relationship of late rectal bleeding after external beam radiotherapy for localized prostate cancer: absolute or relative rectal volume?. Cancer J. 2002;8:62–66
  78. Pollack A, Zagars GK, Starkschall G, et al. Prostate cancer radiation dose response: Results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002;53:1097–1105
  79. Skwarchuk MW, Jackson A, Zelefsky MJ, et al. Late rectal toxicity after conformal radiotherapy of prostate cancer (I): Multivariate analysis and dose-response. Int J Radiat Oncol Biol Phys. 2000;47:103–113
  80. Vargas C, Martinez A, Kestin LL, et al. Dose-volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:1297–1308
  81. Vargas C, Yan D, Kestin LL, et al. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: Use of dose-volume constraints to achieve rectal isotoxicity. Int J Radiat Oncol Biol Phys. 2005;63:141–149
  82. Wachter S, Gerstner N, Goldner G, et al. Rectal sequelae after conformal radiotherapy of prostate cancer: Dose-volume histograms as predictive factors. Radiother Oncol. 2001;59:65–70
  83. Pollack A, Price R, Dong L, et al. Intact prostate cancer: Overview. In:  Mundt AJ,  Roeske JC editor. Intensity Modulated Radiation Therapy (A Clinical Perspective). Hamilton, ON: BC Decker; 2005;p. 436–448
  84. Lawrence TS, Ten Haken RK, Kessler ML, et al. The use of 3-D dose volume analysis to predict radiation hepatitis. Int J Radiat Oncol Biol Phys. 1992;23:781–788
  85. Dawson LA, Normolle D, Balter JM, et al. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53:810–821
  86. Cheng JC, Wu JK, Huang CM, et al. Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: Dosimetric analysis and implication. Int J Radiat Oncol Biol Phys. 2002;54:156–162
  87. Xu ZY, Liang SX, Zhu J, et al. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma. Int J Radiat Oncol Biol Phys. 2006;65:189–195
  88. Liang SX, Zhu XD, Xu ZY, et al. Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: The risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys. 2006;65:426–434
  89. Carr BI. Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: Interim safety and survival data on 65 patients. Liver Transpl. 2004;10:S107–S110
  90. Lewandowski RJ, Thurston KG, Goin JE, et al. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: Response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging. J Vasc Interv Radiol. 2005;16:1641–1651
  91. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): Safety, tumor response, and survival. J Vasc Interv Radiol. 2005;16:1627–1639
  92. Flentje M, Hensley F, Gademann G, et al. Renal tolerance to nonhomogenous irradiation: Comparison of observed effects to predictions of normal tissue complication probability from different biophysical models. Int J Radiat Oncol Biol Phys. 1993;27:25–30

PII: S1053-4296(06)00110-X

doi: 10.1016/j.semradonc.2006.11.009

Seminars in Radiation Oncology
Volume 17, Issue 2 , Pages 131-140 , April 2007

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