The Risks of Breast Radiotherapy and How to Avoid Them

  • Zsuzsanna Kahán
  • Katalin Hideghéty
  • Zoltán Varga
Chapter

Abstract

Besides its benefits, postoperative radiotherapy may cause damage to the irradiated healthy tissues, including inflammatory and/or fibrotic changes or even secondary cancers. Radiation pneumonitis or lung fibrosis may develop shortly after the administration of the radiotherapy. Fibrosis of the breast or the soft tissues exerts an impact on the cosmetic outcome and functioning. Life-threatening radiogenic complications such as ischaemic heart disease, and secondary malignancies may be observed only after a follow-up period of at least 10 years. The radiation damage may be progressive, and depends on various radiotherapy- and patient-related factors or even the systemic therapy. Technical developments including CT-based 3D conformal radiotherapy, IMRT, IGRT, the implementation of patient positioning and immobilization, radiotherapy planning and treatment verification systems in radiotherapy serve to lessen radiation hazards. Despite these beneficial achievements in sparing healthy tissues, radiotherapy still denotes a significant risk, which necessitates a careful estimate of the potential benefit of radiotherapy in each case, and determination of the treatment strategy accordingly.

Keywords

Breast Cancer Patient Perfusion Defect Contralateral Breast Cancer Radiation Pneumonitis Breast Radiotherapy 
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.

References

  1. Anscher MS, Kong FM, Andrews K et al (1998) Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 41:1029–1035PubMedCrossRefGoogle Scholar
  2. Anscher MS, Marks LB, Shafman DT et al (2001) Using transforming growth factor beta-1 during radiotherapy to select patients for dose escalation. J Clin Oncol 19:3758–3765PubMedGoogle Scholar
  3. Azria D, Gourgou S, Sozzi WJ et al (2004) Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients. Br J Cancer 91:1251–1260PubMedCrossRefGoogle Scholar
  4. Azria D, Rosenstein BS, Ozsahin M (2008) Radiation-induced side effects with or without systemic therapies: prime time for prediction of individual radiosensitivity. Int J Radiat Oncol Biol Phys 71:1293–1294PubMedCrossRefGoogle Scholar
  5. Azria D, Belkacemi Y, Romieu G et al (2010) Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial. Lancet Oncol 11:258–265PubMedCrossRefGoogle Scholar
  6. Barber JB, West CM, Kiltie AE, Roberts SA, Scott D (2000) Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy. Radiat Res 153:570–578PubMedCrossRefGoogle Scholar
  7. Begg AC (2009) Molecular targeting and patient individualization. In: Van der Kogel A, Joiner M (eds) Basic clinical radiobiology, 4th edn. Oxford University Press, USAGoogle Scholar
  8. Benda RK, Yasuda G, Sethi A et al (2003) Breast boost: are we missing the target? Cancer 97:905–909PubMedCrossRefGoogle Scholar
  9. Bentzen SM, Overgaard M (1991) Relationship between early and late normal-tissue injury after postmastectomy radiotherapy. Radiother Oncol 20:159–165PubMedCrossRefGoogle Scholar
  10. Bentzen SM, Skoczylas JZ, Overgaard M et al (1996) Radiotherapy-related lung fibrosis enhanced by tamoxifen. J Natl Cancer Inst 88:918–922PubMedCrossRefGoogle Scholar
  11. Bhagamar AK, Beriwal S, Heron DE et al (2009) Initial outcomes analysis for large multicenter integrated cancer network implementation of intensity modulated radiation therapy for breast cancer. Breast J 15:468–474CrossRefGoogle Scholar
  12. Boice JD, Harvey EB, Blettner M et al (1992) Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med 326:781–785PubMedCrossRefGoogle Scholar
  13. Border WA, Noble NA (1994) Transforming growth factor β in tissue fibrosis. N Engl J Med 331:1286–1292PubMedCrossRefGoogle Scholar
  14. Buijsen J, Jager JJ, Bovendeerd J et al (2007) Prone breast irradiation for pendulous breasts. Radiother Oncol 82:337–340PubMedCrossRefGoogle Scholar
  15. Burstein HJ, Bellon JR, Galper S et al (2006) Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer. Int J Radiat Oncol Biol Phys 64:496–504PubMedCrossRefGoogle Scholar
  16. Canney PA, Dean S (1990) Transforming growth factor beta: a promotor of late connective tissue injury following radiotherapy? Br J Radiol 63:620–623 PubMedCrossRefGoogle Scholar
  17. Carlson RW, Allred DC, Anderson BO et al (2009) Breast cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 7:122–192PubMedGoogle Scholar
  18. Caudell JJ, De Los Santos JF, Keene KS, Fiveash JB, Wang W, Carlisle JD, Popple R (2007) A dosimetric comparison of electronic compensation, conventional intensity modulated radiotherapy, and tomotherapy in patients with early-stage carcinoma of the left breast. Int J Radiat Oncol Biol Phys 68:1505–1511PubMedCrossRefGoogle Scholar
  19. Chino JP, Marks LB (2008) Prone positioning causes the heart to be displaced anteriorly within the thorax: implications for breast cancer treatment. Int J Radiat Oncol Biol Phys 70:916–920PubMedCrossRefGoogle Scholar
  20. Colette S, Colette L, Budiharto T et al (2008) Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer—a study based on the EORTC trial 22881-10882 ‘boost versus no boost’. Eur J Cancer 44:2587–2599CrossRefGoogle Scholar
  21. Correa CR, Litt HI, Hwang W-T et al (2007) Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol 25:3031–3037PubMedCrossRefGoogle Scholar
  22. Cuzick J, Stewart H, Rutqvist L et al (1994) Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol 12:447–453PubMedGoogle Scholar
  23. Darby S, McGale P, Peto R et al (2003) Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90,000 Swedish women. BMJ 326:256–257PubMedCrossRefGoogle Scholar
  24. Darby S, McGale P, Taylor CW, Peto R (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 6:557–565PubMedCrossRefGoogle Scholar
  25. Darby SC, Cutter DJ, Boerma M et al (2010) Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys 76:656–65PubMedCrossRefGoogle Scholar
  26. Das I, Cheng EC, Freedman G, Fowble B (1998) Lung and heart volume analyses with CT simulator in radiation treatment of breast cancer. Int J Radiat Oncol Biol Phys 42:11–19PubMedCrossRefGoogle Scholar
  27. Demirci S, Nam J, Hubbs JL et al (2009) Radiation-induced cardiac toxicity after therapy for breast cancer: interaction between treatment era and follow-up duration. Int J Radiat Oncol Biol Phys 73:980–987PubMedCrossRefGoogle Scholar
  28. Dikomey E, Borgmann K, Peacock J, Jung H (2003) Why recent studies relating normal tissue response to individual radiosensitivity might have failed and how new studies should be performed. Int J Radiat Oncol Biol Phys 56:1194–1200PubMedCrossRefGoogle Scholar
  29. Dolinsky C, Glatstein E (2008) Some cases of severe normal tissue toxicity can be anticipated with ablated fractionated radiation with appropriate long-term follow-up. Semin Radiat Oncol 18:229–233PubMedCrossRefGoogle Scholar
  30. Dorr W, Bertmann S, Herrmann T (2005) Radiation induced lung reactions in breast cancer therapy. Modulating factors and consequential effects. Strahlenther Onkol 181:567–573Google Scholar
  31. Dzhugashvili M, Tournay E, Pichenot C et al (2009) 3D-conformal accelerated partial breast irradiation treatment planning: the value of surgical clips in the delineation of the lumpectomy cavity. Radiat Oncol 4:70PubMedCrossRefGoogle Scholar
  32. Early Breast Cancer Trialists’ Collaborative Group(2000) Favourable and unfavourable effects of long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet 355:1757–1771CrossRefGoogle Scholar
  33. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (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 366:2087–2106Google Scholar
  34. Evans ES, Prosnitz RG, Yu X et al (2006) Development of myocardial perfusion defects after radiation therapy for left-sided breats cancer. Int J Radiat Oncol Biol Phys 66:1125–1134PubMedCrossRefGoogle Scholar
  35. Fernet M, Hall J (2008) Predictive markers for normal tissue reactions: fantasy or reality? Cancer Radiother 12:614–618PubMedCrossRefGoogle Scholar
  36. Flannery TW, Nichols EM, Cheston SB et al (2009) Repeat computed tomography simulation to assess lumpectomy cavity volume during whole-breast irradiation. Int J Radiat Oncol Biol Phys 75:751–756PubMedCrossRefGoogle Scholar
  37. Formenti SC, Gidea-Addeo D, Goldberg JD et al (2007) Phase I-II trial of prone accelerated intensity modulated radiation therapy to the breast to optimally spare normal tissue. J Clin Oncol 25:2236–2242PubMedCrossRefGoogle Scholar
  38. Fowble B, Fein DA, Hanlon AL et al (1996) The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer. Int J Radiat Oncol Biol Phys 35:669–677PubMedCrossRefGoogle Scholar
  39. Fuller SA, Haybittle JL, Smith RE, Dobbs HJ (1992) Cardiac doses in post-operative breast irradiation. Radiother Oncol 25:19–24PubMedCrossRefGoogle Scholar
  40. Gagliardi G, Lax I, Ottolenghi A, Rutqvist LE (1996) Long-term cardiac mortality after radiotherapy of breast cancer—application of the relative seriality model. Br J Radiol 69:839–846PubMedCrossRefGoogle Scholar
  41. Gagliardi G, Bjohle J, Lax I et al (2000) Radiation pneumonitis after breast cancer irradiation: analysis of the complication probability using the relative seriality model. Int J Radiat Oncol Biol Phys 46:373–381PubMedCrossRefGoogle Scholar
  42. Gagliardi G, Constine LS, Moiseenko V et al (2010) Radiation dose-volume effects in the heart. Int J Radiat Oncol Biol Phys. 76:S77–S85CrossRefGoogle Scholar
  43. Gao X, Fisher SG, Emami B (2003) Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys 56:1038–1045PubMedCrossRefGoogle Scholar
  44. Gaya AM, Ashford RF (2005) Cardiac complications of radiation therapy. Clin Oncol (R Coll Radiol) 17:153–159 CrossRefGoogle Scholar
  45. Gierga DP, Riboldi M, Turcotte JC, Sharp GC, Jiang SB, Taghian AG, Chen GT (2008) Comparison of target registration errors for multiple image-guided techniques in accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 70:1239–1246PubMedCrossRefGoogle Scholar
  46. Giordano SH, Kuo YF, Freeman JL et al (2005) Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97:419–424PubMedCrossRefGoogle Scholar
  47. Griem KL, Fetherston P, Kuznetsova M et al (2003) Three-dimensional photon dosimetry: a comparison of treatment of the intact breast in the supine and prone position. Int J Radiat Oncol Biol Phys 57:891–899PubMedCrossRefGoogle Scholar
  48. Gulybán A, Kovács P, Sebestyén Z et al (2008) Multisegmented tangential breast fields: a rational way to treat breast cancer. Strahlenther Onkol 184:262–269PubMedCrossRefGoogle Scholar
  49. Gyenes G, Fornander T, Carlens P, Rutqvist LE (1994) Morbidity of ischemic heart disease in early breast cancer 15–20 years after adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 28:1235–1241Google Scholar
  50. Gyenes G, Fornander T, Carlens P et al (1997a) Detection of radiation-induced myocardial damage by technetium-99 m sestamibi scintigraphy. Eur J Nucl Med 24:286–292Google Scholar
  51. Gyenes G, Gagliardi G, Lax I et al (1997b) Evaluation of irradiatied heart volumes in stage I breast cancer patientes treated with postoperative adjuvant radiotherapy. J Clin Oncol 15:1348–1353Google Scholar
  52. Gyenes G, Rutqvist LE, Liedberg A, Fornander T (1998) Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer. Radiother Oncol 48:185–190PubMedCrossRefGoogle Scholar
  53. Hall EJ, Wuu C-S (2003) Radiation-induced second cancers. The impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 56:83–88PubMedCrossRefGoogle Scholar
  54. Hanbeukers B, Borger J, van den Ende P et al (2009) Customized computed tomography-based boost volumes in breast-conserving therapy: use of three-dimensional histologic information for clinical target volume margins. Int J Radiat Oncol Biol Phys 75:757–763PubMedCrossRefGoogle Scholar
  55. Hanna YM, Baglan KL, Stromberg JS et al (2002) Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J 8:149–153PubMedCrossRefGoogle Scholar
  56. Haybittle JL, Brinkley D, Houghton J et al (1989) Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer. BMJ 298:1611–4PubMedCrossRefGoogle Scholar
  57. Hernando ML, Marks LB, Bentel GC et al (2001) Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys 51:650–659PubMedCrossRefGoogle Scholar
  58. Herrick JS, Neill CJ, Rosser PF (2008) A comprehensive clinical 3-dimensional dosimetric analysis of forward planned IMRT and conventional wedge planned techniques for intact breast radiotherapy. Med Dosim 33:62–70PubMedCrossRefGoogle Scholar
  59. Ho AY, Atencio DP, Peters S et al (2006) Genetic predictors of adverse radiotherapy effects: the Gene-PARE project. Int J Radiat Oncol Biol Phys 65:646–655PubMedCrossRefGoogle Scholar
  60. Højris I, Andersen J, Overgaard M et al (2000) Late treatment-related morbidity in breast cancer patients randomized to postmastectomy radiotherapy and systemic treatment versus systemic treatment alone. Acta Oncol 39:355–372PubMedCrossRefGoogle Scholar
  61. Holli K, Pitkanen M, Jarvenpaa R et al (2002) Early skin and lung reactions in breast cancer patients after radiotherapy: prospective study. Radiother Oncol 64:163–169PubMedCrossRefGoogle Scholar
  62. Hooning MJ, Aleman BM, van Rosmalen AJ, Kuenen MA, Klijn FE, van Leeuwen FE (2006) Cause-specific mortality in long-term survivors of breast cancer: a 25-year follow-up study. Int J Radiat Oncol Biol Phys 64:1081–1091PubMedCrossRefGoogle Scholar
  63. Hopwood P, Haviland JS, Sumo G et al (2010) Comparison of patient-reported breast, arm, and shoulder symptoms and body image after radiotherapy for early breast cancer: 5-year follow-up in the randomised Standardisation of Breast Radiotherapy (START) trials. Lancet Oncol 11:231–240PubMedCrossRefGoogle Scholar
  64. Host H, Brennhovd IO, Loeb M (1986) postoperative radiotherapy in breast cancer -long–term results from the Oslo study. Int J Radiat Oncol Biol Phys 12:727–732PubMedCrossRefGoogle Scholar
  65. Huang E-Y, Wang C-J, Chen H-C et al (2000) Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors. Radiother Oncol 57:91–96PubMedCrossRefGoogle Scholar
  66. Hurkmans CW, Borger JH, Bos LJ et al (2000) Cardiac and lung complication probabilities after breast cancer irradiation. Radiother Oncol 55:145–151PubMedCrossRefGoogle Scholar
  67. Hurkmans CW, Cho BC, Damen E et al (2002) Reduction of cardiac and lung complication probabilities after breast irradiation using conformal radiotherapy with or without intensity modulation. Radiother Oncol 62:163–171PubMedCrossRefGoogle Scholar
  68. Hurkmans C, Admiraal M, van der Sangen M, Dijkmans I (2009) Significance of breast boost volume changes during radiotherapy in relation to current clinical interobserver variations. Radiother Oncol 90:60–65PubMedCrossRefGoogle Scholar
  69. Inskip PD, Stovall M, Flannery JT (1994) Lung cancer risk and radiation dose among women treated for breast cancer. J Natl Cancer Inst 86:983–988PubMedCrossRefGoogle Scholar
  70. Ishitobi M, Komoike Y, Motomura K et al (2009) Retrospective analysis of concurrent vs. sequential administration of radiotherapy and hormone therapy using aromatase inhibitor for hormone receptor-positive postmenopausal breast cancer. Anticancer Res 29:4791–4794PubMedGoogle Scholar
  71. Jaén J, Vázquez, Alonso E et al (2006) Changes in pulmonary function after incidental lung irradiation for breast cancer: a prospective study. Int J Radiat Oncol Biol Phys 65:1381–1388PubMedCrossRefGoogle Scholar
  72. Jain P, Marchant T, Green M, Watkins G, Davies J, McCarthy C, Loncaster J, Stewart A, Magee B, Moore C, Price P (2009) Inter-fraction motion and dosimetric consequences during breast intensity-modulated radiotherapy (IMRT). Radiother Oncol 90:93–98PubMedCrossRefGoogle Scholar
  73. Johansen J, Overgaard J, Rose C et al (2002) Cosmetic outcome and breast morbidity in breast-conserving treatment. Acta Oncol 41:369–380PubMedCrossRefGoogle Scholar
  74. Johansen J, Overgaard J, Overgaard M (2007) Effect of systemic treatment on cosmetic outcome on late normal-tissue reactions after breast conservation. Acta Oncol 46:525–533PubMedCrossRefGoogle Scholar
  75. Jones JM, Ribeiro GG (1989) Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy. Clin Radiol 40:204–208PubMedCrossRefGoogle Scholar
  76. Kader HA, Truong PT, Pai R et al (2008) When is CT-based postoperative seroma most useful to plan partial breast radiotherapy? Evaluation of clinical factors affecting seroma volume and clarity. Radiother Oncol 72:1064–1069Google Scholar
  77. Kahán Z, Csenki M, Varga Z et al (2007) The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 68:673–681PubMedCrossRefGoogle Scholar
  78. Kim LH, Decesare S, Vicini F, Yan D (2010) Effect of lumpectomy cavity volume change on the clinical target volume for accelerated partial breast irradiation: a deformable registration study. Int J Radiat Oncol Biol Phys 78(4):1121–1126PubMedCrossRefGoogle Scholar
  79. Kirby AM, Yarnold JR, Evans PM et al (2009) Tumor bed delineation for partial breast and breast boost radiotherapy planned in the prone position: what does MRI add to X-ray CT localization of titanium clips placed in the excision cavity wall? Int J Radiat Oncol Biol Phys 74:1276–1282PubMedCrossRefGoogle Scholar
  80. Kiricuta IC, Gotz U, Schwab F et al (2000) Target volume definition and target conformal irradiation technique for breast cancer patients. Acta Oncol 39:429–436PubMedCrossRefGoogle Scholar
  81. Koc M, Polat P, Suma S (2002) Effects of tamoxifen on pulmonary fibrosis after cobalt-60 radiotherapy in breast cancer patients. Radiother Oncol 64:171–175PubMedCrossRefGoogle Scholar
  82. Korreman SS, Pedersen AN, Josipović M et al (2006) Cardiac and pulmonary complication probabilities for breast cancer patients after routine end-inspiration gated radiotherapy. Radiother Oncol 80:257–262PubMedCrossRefGoogle Scholar
  83. Krauss DJ, Kestin LL, Raff G et al (2005) MRI-based volumetric assessment of cardiac anatomy and dose reduction via active breathing control during irradiation for left-sided breast cancer. Int J Radiat Oncol Biol Phys 61:1243–1250PubMedCrossRefGoogle Scholar
  84. Kurtman C, Andrieu MN, Hicsönmez A, Celebioglu B (2003) Three-dimensional conformal breast irradiation in the prone position. Braz J Med Biol Res 36:1441–1446PubMedCrossRefGoogle Scholar
  85. Kwa SL, Lebesque JV, Theuws JC et al (1998) Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys 42:1–9 PubMedCrossRefGoogle Scholar
  86. Landau D, Adams EJ, Webb S, Ross G (2001) Cardiac avoidance in breast radiotherapy: a comparison of simple shielding techniques with intensity-modulated radiotherapy. Radiother Oncol 60:247–255PubMedCrossRefGoogle Scholar
  87. Levi F, Randimbison L, Te VC et al (2006) Cancer risk after radiotherapy for breast cancer. Br J Cancer 95:390–392PubMedCrossRefGoogle Scholar
  88. Li C, Wilson PB, Levine E et al (1999) TGF-β1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. Int J Cancer 84:155–159PubMedCrossRefGoogle Scholar
  89. Lilla C, Ambrosone CB, Kropp S et al (2007) Predictive factors for late normal tissue complications following radiotherapy for breast cancer. Breast Cancer Res Treat 106:143–150PubMedCrossRefGoogle Scholar
  90. Lin A, Moran JM, Marsh RB et al (2008) Evaluation of multiple breathing states using a multiple instance geometry approximation (MIGA) in inverse-planned optimization for locoregional breast treatment. Int J Radiat Oncol Biol Phys 72:610–616PubMedCrossRefGoogle Scholar
  91. Lind PA, Wennberg B, Gagliardi G et al (2001) Pulmonary complications following different radiotherapy techniques for breast cancer, and the association to irradiated lung volume and dose. Breast Cancer Res Treat 68:199–210PubMedCrossRefGoogle Scholar
  92. Lind PA, Marks LB, Hardenbergh PH et al (2002) Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys 52:137–143PubMedCrossRefGoogle Scholar
  93. Lind PA, Pagnanelli R, Marks LB et al (2003) Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution. Int J Radiat Oncol Biol Phys 55:914–925PubMedCrossRefGoogle Scholar
  94. Lind PA, Wennberg B, Gagliardi G et al (2006) ROC curves and evaluation of radiation-induced pulmonary toxicity in breast cancer. Int J Radiat Oncol Biol Phys 64:765–770 PubMedCrossRefGoogle Scholar
  95. Lingos TI, Recht A, Vicini F et al (1991) Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 21:355–360PubMedCrossRefGoogle Scholar
  96. Livi L, Borghesi S, Saieva C et al (2009) Radiotherapy timing in 4,820 patients with breast cancer: University of Florence experience. Int J Radiat Oncol Biol Phys 73:365–369PubMedCrossRefGoogle Scholar
  97. Livi L, Buonamici FB, Simontacchi G et al (2010) Accelerated partial breast irradiation with IMRT: new technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. Int J Radiat Oncol Biol Phys 77:509–515PubMedCrossRefGoogle Scholar
  98. Mannino M, Yarnold JR (2009) Local relapse rates are falling after breast conserving surgery and systemic therapy for early breast cancer: can radiotherapy ever be safely withheld? Radiother Oncol 90:14–22PubMedCrossRefGoogle Scholar
  99. Marhin W, Wai E, Tyldesley S (2007) Impact of fraction size on cardiac mortality in women treated with tangential radiotherapy for localized breast cancer. Int J Radiat Oncol Biol Phys 67:1–7CrossRefGoogle Scholar
  100. Marks LB, Yu X, Prosnitz RG et al (2005) The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys 63:214–223PubMedCrossRefGoogle Scholar
  101. Merchant TE, McCormick B (1994) Prone position breast irradiation. Int J Radiat Oncol Biol Phys 30:197–203PubMedCrossRefGoogle Scholar
  102. Moody AM, Mayles WP, Bliss JM et al (1994) The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity. Int J Radiat Oncol Biol Phys 33:106–112Google Scholar
  103. Moon SH, Shin KH, Kim TH et al (2009) Dosimetric comparison of four different external beam partial breast irradiation techniques: three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, helical tomotherapy, and proton beam therapy. Radiother Oncol 90:66–73PubMedCrossRefGoogle Scholar
  104. Moran JM, Ben-David MA, Marsh RB et al (2009) Accelerated partial breast irradiation: what is dosimetric effect of advanced technology approaches? Int J Radiat Oncol Biol Phys 75:294–301PubMedCrossRefGoogle Scholar
  105. Muren LP, Maurstad G, Hafslund R et al (2002) Cardiac and pulmonary doses and complication probabilities in standard and conformal tangential irradiation in conservative management of breast cancer. Radiother Oncol 62:173–183PubMedCrossRefGoogle Scholar
  106. Nixon A, Manola J, Gelman R et al (1998) No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques. J Clin Oncol 16:1374–1379PubMedGoogle Scholar
  107. Novakova-Jiresova A, Van Gameren MM, Coppes RP et al (2004) Transforming growth factor-beta plasma dynamics and post-irradiation lung injury in lung cancer patients. Radiother Oncol 71:183–189PubMedCrossRefGoogle Scholar
  108. Offersen BV, Overgaard M, Kroman N, Overgaard J (2009) Accelerated partial breast irradiation as a part of breast conserving therapy of early breast cancer: a systematic review. Radiother Oncol 90:1–13PubMedCrossRefGoogle Scholar
  109. Oh KS, Kong FM, Griffith KA et al (2006) Planning the breast tumor bed boost: changes in the excision cavity volume and surgical scar location after breast-conserving surgery and whole-breast irradiation. Int J Radiat Oncol Biol Phys 66:680–686PubMedCrossRefGoogle Scholar
  110. Ooi GC, Kwong DL, Ho JC et al (2001) Pulmonary sequelae of treatment for breast cancer: a prospective study. Int J Radiat Oncol Biol Phys 50:411–419PubMedCrossRefGoogle Scholar
  111. Oppitz U, Baier K, Wulf J, et al (2001) The in vitro colony assay: a predictor of clinical outcome. Int J Radiat Biol 77:105–110PubMedCrossRefGoogle Scholar
  112. Orzan F, Brusca A, Conte MR et al (1993) Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. Br Heart J 69(6):496–500PubMedCrossRefGoogle Scholar
  113. Ozsahin M, Crompton NE, Gourgou S et al (2005) CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients. Clin Cancer Res 11:7426–7433PubMedCrossRefGoogle Scholar
  114. Ozsahin M, Belkacemi Y, Rosenstein B et al (2007) Radiation-induced CD8 T-lymphocyte apoptosis yield predicts toxicities after adjuvant treatment with concurrent and sequential radiotherapy and letrozole in postmenopausal women with hormone receptor positive breast cancers: preliminary results of the multicenter phase II randomized trial (COHORT) [Abstract]. Breast Cancer Res Treat 106(Suppl.):166Google Scholar
  115. Paszat LF, Mackillop WJ, Groome PA et al (1999) Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada. Int J Radiat Oncol Biol Phys 43:755–762PubMedCrossRefGoogle Scholar
  116. Patel RR, Becker SJ, Das RK, Mackie TR (2007) A dosimetric comparison of accelerated partial breast irradiation techniques: multicatheter interstitial brachytherapy, three-dimensional conformal radiotherapy, and supine versus prone helical tomotherapy. Int J Radiat Oncol Biol Phys 68:935–942PubMedCrossRefGoogle Scholar
  117. Penninkhof J, Quint S, Boer H, Mens JW, Heijmen B, Dirkx M (2009) Surgical clips for position verification and correction of non-rigid breast tissue in simultaneously integrated boost (SIB) treatments. Radiother Oncol 90:110–115PubMedCrossRefGoogle Scholar
  118. Pierce LJ (2005) The use of radiotherapy after mastectomy: a review of the literature. J Clin Oncol 23:1706–1717PubMedCrossRefGoogle Scholar
  119. Pierce LJ, Butler JB, Martel MK et al (2002) Postmastectomy radiotherapy of the chest wall: dosimetric comparison of common techniques. Int J Radiat Oncol Biol Phys 52:1220–1230PubMedCrossRefGoogle Scholar
  120. Prendergast B, Indelicato DJ, Grobmyer SR et al (2009) The dynamic tumor bed: volumetric changes in the lumpectomy cavity during breast-conserving therapy. J Radiat Oncol Biol Phys 74:695–701CrossRefGoogle Scholar
  121. Prosnitz RG, Chen H, Marks LB (2005) Cardiac toxicity following thoracic radiation. Semin Oncol 32(Suppl 3):S71–S80PubMedCrossRefGoogle Scholar
  122. Recht A, Ancukiewicz M, El-Din MAA et al (2009) Lung dose-volume parameters and the risk of pneumonitis for patients treated with accelerated partial-breast irradiation using three-dimensional conformal radiotherapy. J Clin Oncol 27:3887–3893PubMedCrossRefGoogle Scholar
  123. Renella R, Verkooijen HM, Fioretta G et al (2006) Increased risk of acute myeloid leukemia after treatment for breast cancer. Breast 15:614–619PubMedCrossRefGoogle Scholar
  124. Roychoudhuri R, Evans HM, Robinson D, Moller H (2004) Radiation-induced malignancies following radiotherapy for breast cancer. Br J Cancer 91:868–872PubMedGoogle Scholar
  125. Rubino, Shamsaldin A, Lê MG et al (2005) Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res Treat 89:277–288PubMedCrossRefGoogle Scholar
  126. Russell NS, Grummels A, Hart AA et al (1998) Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer. Int J Radiat Biol 73:661–670PubMedCrossRefGoogle Scholar
  127. Rutqvist LE, Lax I, Fornander T, Johansson H (1992) Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alona in primary breast cancer. Int J Radiat Oncol Biol Phys 22:887–896PubMedCrossRefGoogle Scholar
  128. Seppenwoolde Y, Lebesque JV, de Jaeger K et al (2003) Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys 55:724–735PubMedCrossRefGoogle Scholar
  129. Shapiro CL, Hardenbergh PH, Gelman R et al (1998) Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol 16:3493–3501PubMedGoogle Scholar
  130. Skoczylas JZ, Bentzen SM, Overgaard M et al (2000) Time course of radiological lung density changes after postmastectomy radiotherapy. Acta Oncol 39:181–187PubMedCrossRefGoogle Scholar
  131. START Trialists’ Group, Bentzen SM, Agrawal RK, Aird EG et al (2008a) The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 9:331–341CrossRefGoogle Scholar
  132. START Trialists’ Group, Bentzen SM, Agrawal RK, Aird EG et al (2008b) The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 371:1098–1107CrossRefGoogle Scholar
  133. Stegman LD, Beal KP, Hunt MA et al (2007) Long-term clinical outcomes of whole-breast irradiation delivered in the prone position. Int J Radiat Oncol Biol Phys 68:73–81PubMedCrossRefGoogle Scholar
  134. Stewart JR, Fajardo LF, Gilette SM, Constine LS (1995) Radiation injury to the heart. Int J Radiat Oncol Biol Phys 31:1205–1211PubMedCrossRefGoogle Scholar
  135. Storm HH, Andersson M, Boice JD Jr et al (1992) Adjuvant radiotherapy and risk of contralateral breast cancer. J Natl Cancer Inst 84:1245–1250PubMedCrossRefGoogle Scholar
  136. Struikmans H, Wárlám-Rodenhuis C, Stam T et al (2005) Interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation. Radiother Oncol 76:293–299PubMedCrossRefGoogle Scholar
  137. Svane G, Rotstein S, Lax I (1995) Influence of radiation therapy on lung tissue in breast cancer patients. CT-assessed density changes 4 years after completion of radiotherapy. Acta Oncol 34:845–849PubMedCrossRefGoogle Scholar
  138. Taghian AG, Assaad SI, Niemierko A et al (2001) Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 93:1806–1811PubMedCrossRefGoogle Scholar
  139. Taylor ME, Perez CA, Halverson KJ et al (1995) Factors influencing cosmetic results after conservation therapy for breast cancer. Int J Radiat Oncol Biol Phys 31:753–764PubMedCrossRefGoogle Scholar
  140. Taylor CW, Nisbet A, McGale P et al (2009) Cardiac doses from Swedish breast cancer radiotherapy since the 1950s. Radiother Oncol 90:127–135PubMedCrossRefGoogle Scholar
  141. Tell R, Edgren MR, Sverrisdottir A et al (2003) Radiation-induced cell cycle response in lymphocytes is not related to clinical side-effects in breast cancer patients. Anticancer Res 23:3077–3083PubMedGoogle Scholar
  142. Theuws JC, Kwa SL, Wagenaar AC et al (1998) Dose-effect relations for early local pulmonary injury after irradiation for malignant lymphoma and breast cancer. Radiother Oncol 48:33–43PubMedCrossRefGoogle Scholar
  143. Toledano A, Garaud P, Serin D et al (2006) Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: long-term results of the ARCOSEIN multicenter randomized srudy. Int J Radiat Oncol Biol Phys 65:324–332PubMedCrossRefGoogle Scholar
  144. Tsougos I, Mavroidis P, Rajala J et al (2005) Evaluation of dose-response models and parameters predicting radiation. Phys Med Biol 50:3535–3554PubMedCrossRefGoogle Scholar
  145. Vågane R, Bruland ØS, Fosså SD, Olsen DR (2008) Radiological and functional assessment of radiation-induced pulmonary damage following breast irradiation. Acta Oncol 47:248–254PubMedCrossRefGoogle Scholar
  146. van Mourik AM, Elkhuizen PH, Minkema D et al (2010) Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines. Radiother Oncol 94:286–291PubMedCrossRefGoogle Scholar
  147. Varga Z, Hideghéty K, Mező T et al (2009) Individual positioning: a comparative study of adjuvant breast radiotherapy in the prone versus supine position. Int J Radiat Oncol Biol Phys 75:94–100PubMedCrossRefGoogle Scholar
  148. Varga Z, Cserháti A, Kelemen G (2010) The role of systemic therapy in the development of lung sequelae after conformal radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys (accepted for publication) Google Scholar
  149. Wazer DE, DiPetrillo T, Schmidt-Ullrich R et al (1992) Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma. J Clin Oncol 10:356–363PubMedGoogle Scholar
  150. Wazer DE, Morr J, Erban JK et al (1997) The effects of postradiation treatment with tamoxifen on local control and cosmetic outcome in the conservatively treated breast. Cancer 80:732–740PubMedCrossRefGoogle Scholar
  151. Wennberg B, Gagliardi G, Sundbom L et al (2002) Early response of lung in breast cancer irradiation: radiologic density changes measured by CT and symptomatic radiation pneumonitis. Int J Radiat Oncol Biol Phys 52:1196–1206PubMedCrossRefGoogle Scholar
  152. Whelan TJ, Pignol J-P, Levine MN et al (2010) Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 362:513–520PubMedCrossRefGoogle Scholar
  153. Whipp EC, Halliwell M (2008) Magnetic resonance imaging appearances in the postoperative breast: the clinical target volume-tumor and its relationship to the chest wall. Int J Radiat Oncol Biol Phys 72:49–57PubMedCrossRefGoogle Scholar
  154. Winer EP, Hudis C, Burstein HJ et al (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23:619–629PubMedCrossRefGoogle Scholar
  155. Yang TI, Elkhuizen PH, Minkema D et al (2009) Clinical factors associated with seroma volume reduction in breast-conserving therapy for early-stage breast cancer: a multi-institutional analysis. Int J Radiat Oncol Biol Phys.74:695–701CrossRefGoogle Scholar
  156. Yu TK, Whitman GJ, Thames HD et al (2004) Clinically relevant pneumonitis after sequential paclitaxel-based chemotherapy and radiotherapy in breast cancer patients. J Natl Cancer Inst 96:1676–1681PubMedCrossRefGoogle Scholar
  157. Zablotska LB, Neugut AI (2003) Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast cancer. Cancer 97:1404–1411PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Zsuzsanna Kahán
    • 1
  • Katalin Hideghéty
    • 1
  • Zoltán Varga
    • 1
  1. 1.Department of OncotherapyUniversity of SzegedSzegedHungary

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