Complications and Toxicity of Radiotherapy for the Breast, Lung and Heart

  • John T. Murchison
  • Edwin J. R. van Beek
Part of the Medical Radiology book series (MEDRAD)


The side effects and toxicity of radiotherapy administered to the thorax can be separated into early and late types. The most important early effect is radiation pneumonitis which is dependent on various factors, the most important of which is dose. In the most severe cases, this can prove fatal, and the risk of developing severe radiation pneumonitis can limit therapeutic options. Early acute cardiac and cardiac side effects can also occur. The longer-term sequelae of thoracic irradiation include pulmonary radiation fibrosis, premature ischemic heart, cardiac valvular disease, radiation osteonecrosis, oesophageal strictures and the development of second cancers. These side effects are particularly relevant in the treatment of cancers of children and young adults especially in the treatment of lymphoma.


Breast Cancer Radiation Field Radiation Pneumonitis Constrictive Pericarditis Thoracic 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.


  1. Bachman AL, Macken K (1959) Pleural effusions following supervoltage radiation for breast carcinoma. Radiology 72:1157–1164Google Scholar
  2. Bates EL, Bragg CM, Wild JM, Hatton MQ, Ireland RH (2009) Functional image-based radiotherapy planning for non-small cell lung cancer: a simulation study. Radiother Oncol 93:32–36PubMedCentralCrossRefPubMedGoogle Scholar
  3. Bell J, McGivern D (1988) Bullimore, et al Diagnostic imaging of post-irradiation change in the chest. Clin Radiol 39:109–119CrossRefPubMedGoogle Scholar
  4. Billiet C, Peeters S, Ruysscher DD (2014) Focus on treatment complications and optimal management: radiation oncology. Transl Lung Cancer Res 3:187–191PubMedCentralPubMedGoogle Scholar
  5. Bouillon K, Haddy N, Delaloge S et al (2011) Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol 57:445–452CrossRefPubMedGoogle Scholar
  6. Claude L, Perol D, Ginestet C, Falchero L, Arpin D, Vincent M et al (2004) A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: clinical and dosimetric factors analysis. Radiother Oncol 71:175–181CrossRefPubMedGoogle Scholar
  7. Darby SC, 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 6:557–565CrossRefPubMedGoogle Scholar
  8. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368:987–998CrossRefPubMedGoogle Scholar
  9. Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and on 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106CrossRefGoogle Scholar
  10. Early Breast Cancer Trialists’ Collaborative Group (2011) Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378:1707–1716CrossRefGoogle Scholar
  11. Farr KP, Kramer S, Khalil AA, Morsing A, Grau C (2015) Role of perfusion SPECT in prediction and measurement of pulmonary complications after radiotherapy for lung cancer. Eur J Nucl Med Mol Imaging 42:1315–1324CrossRefPubMedGoogle Scholar
  12. Fowble B, Hanlon A, Freedman G, Nicolaou N, Anderson P (2001) Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk. Int J Radiat Oncol Biol Phys 51:679–690CrossRefPubMedGoogle Scholar
  13. Galper S, Gelman R, Recht A, Silver B, Kohli A, Wong JS, van Buren T, Baldini EH, Harris JR (2002) Second nonbreast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys 52:406–414CrossRefPubMedGoogle Scholar
  14. Glanzmann C, Kaufmann P, Jenni R, Hess OM, Huguenin P (1998) Cardiac risk after mediastinal irradiation for Hodgkin’s disease. Radiother Oncol 46:51–62CrossRefPubMedGoogle Scholar
  15. Gustavsson A, Osterman B, Cavallin-Stahl E (2003) A systematic overview of radiation therapy effects in Hodgkin’s Lymphoma. Acta Oncologica 42:589–604Google Scholar
  16. Hancock SL, Hoppe RT (1996) Long-term complications of treatment and causes of mortality after Hodgkin’s disease. Semin Radiat Oncol 6:225–242CrossRefPubMedGoogle Scholar
  17. Hancock SL, Tucker MA, Hoppe RT (1993) Breast cancer after treatment of Hodgkin’s disease. J Natl Cancer Inst 85:1530–1537CrossRefGoogle Scholar
  18. Heidenreich PA, Schnittger I, Strauss HW, Vagelos RH, Lee BK, Mariscal CS, Tate DJ, Horning SJ, Hoppe RT, Hancock SL (2007) Screening for coronary artery disease after mediastinal irradiation for Hodgkin’s Disease. J Clin Oncol 25:43–49CrossRefPubMedGoogle Scholar
  19. Hooning MJ, Botma A, Aleman BMP et al (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99:365–375CrossRefPubMedGoogle Scholar
  20. Hoppe RT (1997) Hodgkin’s disease: complications of therapy and excess mortality. Ann Oncol 8(Suppl 1):115–118 (R1/2498)Google Scholar
  21. Inoue T, Shiomi H, Oh RJ (2015) Stereotactic body radiotherapy for stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis. J Radiat Res 56:727–734Google Scholar
  22. Inskip PD, Stoval M, Flannery JT (1994) Lung cancer risk and radiation dose among women treated for breast cancer. J Natl Cancer Inst 86:983–988CrossRefPubMedGoogle Scholar
  23. Inskip PD, Robison LL, Stovall M et al (2009) Radiation dose and breast cancer risk in the childhood Cancer Survivor study. J Clin Oncol 27:3901–3907PubMedCentralCrossRefPubMedGoogle Scholar
  24. Ireland RH, Woodhouse N, Hoggard N, Swinscoe JA, Foran BH, Hatton MQ, Wild JM (2008) An image acquisition and registration strategy for the fusion of hyperpolarized helium-3 MRI and X-ray CT images of the lung. Phys Med Biol 53:6055–6063PubMedCentralCrossRefPubMedGoogle Scholar
  25. Johansson S, Svensson H, Denekamp J (2002) Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients. Int J Radiat Oncol Biol Phys 52:1207–1219CrossRefPubMedGoogle Scholar
  26. King V, Constine LD, Clark D et al (1996) Symptomatic coronary artery disease after mantle irradiation for Hodgkin’s disease. Int J Radiat Oncol Biol Phys 36:881–889CrossRefPubMedGoogle Scholar
  27. Kirova YM, Gambotti L, de Rycke Y, Vilcoq JR, Asselain B, Fouquet A (2007) Risk of second malignancies after adjuvant chemotherapy for breast cancer: a large-scale, single-institution review. Int J Radiat Oncol Biol Phys 68:359–363CrossRefPubMedGoogle Scholar
  28. Kirova YM, de Rycke Y, Gambotie L, Pierga JY, Asselain B, Fourquet A, Institut Curie Breast Cancer Study Group (2008) Second malignancies after breast cancer: the impact of different treatment modalities. Br J Cancer 98:870–874PubMedCentralCrossRefPubMedGoogle Scholar
  29. Lamoureux K (1975) Increased clinically symptomatic pulmonary radiation reactions with adjuvant chemotherapy. Cancer Chemother Res 36:946–949 (part1)Google Scholar
  30. Libshitz HI, Shuman LS (1984) Radiation-induced pulmonary change: CT findings. J Comput Assist Tomogr 8:15–19CrossRefPubMedGoogle Scholar
  31. Meadows AT (2001) Second tumours. Eur J Cancer 37:2074–2079CrossRefPubMedGoogle Scholar
  32. Montgomery D, Campbell S, Cheng K, et al (2013) Predicting the Occurrence of Radiation Induced Pneumonitis by Texture Analysis of CT Images from Lung Cancer Patients.. Published in the Proceedings of the Fifth International Workshop on Pulmonary Image Analysis, held in conjunction with the MICCAI 2013 meeting in Nagoya, 26 Sept 2013Google Scholar
  33. Mulrooney DA, Nunnery SE, Armstrong GT, Ness KK, Srivastava D, Donovan FD, Kurt BA, Metzger ML, Krasin MJ, Joshi V, Durand JB, Robison LL, Hudson MM, Flamm SD (2014) Cancer 120:3536–3544CrossRefPubMedGoogle Scholar
  34. Murofushi KN, Oguchi M, Gosho M, Kozuka T, Sakurai H (2015) Radiation Induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome in breast cancer patients is associated with age. Radiat Oncol 10:103PubMedCentralCrossRefPubMedGoogle Scholar
  35. Nahum AE (2015) The radiobiology of hypofractionation. Clin Oncol 27:260–269CrossRefGoogle Scholar
  36. Omer H, Sulieman A, Alzimami K (2015) Risk of lung fibrosis and pneumonitis after post mastectomy electron radiotherapy. Radiat Prot Dosimetry 165:499–502Google Scholar
  37. Orzan F, Brusca A, Conte MR, Prebitero P, Figliomeni MC (1993) Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. Br Heart J 69:496–500PubMedCentralCrossRefPubMedGoogle Scholar
  38. Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M et al (2013) Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 85:444–450PubMedCentralCrossRefPubMedGoogle Scholar
  39. Park KJ, Chung JY, Chun MS, Suh JH (2000) Radiation-induced lung disease and the impact of radiation methods on imaging features. Radiographics 20:83–98CrossRefPubMedGoogle Scholar
  40. Reinders JG, Heijmen BJM, Olofsen-can Acht MJJ et al (1999) Ischaemic heart disease after mantlefield irradiation for Hodgkin’s disease in long-term follow-up. Radiother Oncol 51:35–42CrossRefPubMedGoogle Scholar
  41. Rodriques G, Lock M, D’Souza D et al (2007) Prediction of radiation pneumonitis, derived from a combined analysis of RTOG 9311 and institutional data. Int J Radiat Oncol Biol Phys 69:985–992CrossRefGoogle Scholar
  42. Santyr G, Fox M, Think K, Hegarty E, Ouriadov A, Jensen M et al (2014) Anatomical, functional and metabolic imaging of radiation-induced lung injury using hyperpolarized MRI. NMR Biomed 27:1515–1524CrossRefPubMedGoogle Scholar
  43. Saxena P, Joyce LD, Daly RC, Kushwaha SS, Schirger JA, Rosedahl J, Dearani JA, Kara T, Edwards BS (2014) Cardiac transplantation for radiation-induced cardiomyopathy: the Mayo Clinic experience. Ann Thorac Surg 98:2115–2121CrossRefPubMedGoogle Scholar
  44. Swerdlow AJ, Douglas AJ, Vaughan Hudson G et al (1993) Risk of second primary cancer in after Hodgkin’s disease in patients in the British National Lymphoma Investigation: relationships to host factors, histology, and stage of Hodgkin’s disease, and splenectomy. Br J Cancer 68:1006–1011PubMedCentralCrossRefPubMedGoogle Scholar
  45. Swerdlow AJ, Barber JA, Vaughan Hudson G et al (2000) Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 18:498–509PubMedGoogle Scholar
  46. Tjessem KH, Bosse G, Fossa K, Reinertsen KV, Fossa SD, Johansen S, Fossa A (2015) Coronary calcium score in 12-year breast cancer survivors after adjuvant radiotherapy with low to moderate heart exposure – relationship to cardiac radiation dose and cardiovascular risk factors. Radiother Oncol 114:328–334CrossRefPubMedGoogle Scholar
  47. Travis LB, Hill D, Dores GM et al (2003) Breast Cancer following radiotherapy and chemotherapy among young women with Hodgkin Disease. JAMA 290:465–475CrossRefPubMedGoogle Scholar
  48. Travis LB, Hill D, Dores GM et al (2005) Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma. J Natl Cancer Inst 97:1428–1437CrossRefPubMedGoogle Scholar
  49. van Leeuwen FE, Klokman WJ, Hagenbeek A et al (1994) Second cancer risk following Hodgkin’s disease: a 20-year follow-up study. J Clin Oncol 12:312–325PubMedGoogle Scholar
  50. van Leeuwen FE, Klokman WJ, van’t Veer MB et al (2000) Long-term risk of second malignancy in survivors of Hodgkin’s disease treated during adolescence or young adulthood. J Clin Oncol 18:487–497PubMedGoogle Scholar
  51. Vogelius IR, Bentzen A (2012) Literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis. Acta Oncol 51:975–983PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of RadiologyRoyal Infirmary of EdinburghEdinburghUK
  2. 2.Queen’s Medical Research InstituteUniversity of EdinburghEdinburghUK

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