International Journal of Radiation Oncology * Biology * Physics
Volume 63, Issue 1 , Pages 214-223 , 1 September 2005

The incidence and functional consequences of RT-associated cardiac perfusion defects

Portions of this work were presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, New Orleans, LA, October 6–10, 2002, and at the 45th Annual Meeting of American Society for Therapeutic Radiology and Oncology, Salt Lake City, UT, October 18–23, 2003.

  • Lawrence B. Marks, M.D.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
    • Corresponding Author InformationReprint requests to: Lawrence B. Marks, M.D., Department of Radiation Oncology, Box 3085, Duke University Medical Center, Durham, NC 27710. Tel: (919) 668-5640; Fax: (919) 668-7345
  • ,
  • Xiaoli Yu, M.D.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Robert G. Prosnitz, M.D.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Su-Min Zhou, Ph.D.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Patricia H. Hardenbergh, M.D.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Michael Blazing, M.D.

      Affiliations

    • Department of Cardiology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Donna Hollis, M.S.

      Affiliations

    • Department of Biostatistics, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Pehr Lind, M.D., Ph.D.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Andrea Tisch, B.A.

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
  • ,
  • Terence Z. Wong, M.D., Ph.D.

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC
  • ,
  • Salvador Borges-Neto, M.D.

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC

Received 24 August 2004 ,Revised 10 January 2005 ,Accepted 18 January 2005.

References 

  1. Fisher B , Anderson S , Bryant J , et al.   Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy and lumpectomy plus irradiation for the treatment of invasive breast cancer . N Engl J Med . 2002;347:1233–1241
  2. Lichter AS , Lippman ME , Danforth D . Mastectomy versus breast conserving therapy in the treatment of stage I and II carcinoma of the breast (A randomized trial at the National Cancer Institute) . J Clin Oncol . 1992;10:976–983
  3. van Dongen JA , Voogd AC , Fentiman IS , et al.   Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy (European Organization for Research and Treatment of Cancer 10801 trial) . J Natl Cancer Inst . 2002;92:1143–1150
  4. National Institute of Health Concensus Development Panel . Treatments of early stage breast cancer . J Natl Cancer Inst Monograph . 1992;11:1
  5. Overgaard M , Hansen PS , Overgaard J , et al.   Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy . N Engl J Med . 1997;337:949–955
  6. Overgaard M , Jensen M-J , Overgaard J , et al.   Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen (Danish Breast Cancer Cooperative Group DBCG 82c randomized trial) . Lancet . 1999;353: 1651–1647
  7. Ragaz J , Jackson SM , Nhu L , et al.   Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer . N Engl J Med . 1997;337:956–962
  8. Cuzick J , Stewart H , Rutqvist L , et al.   Cause specific mortality in long term survivors of breast cancer who participated in trials of radiotherapy . J Clin Oncol . 1994;12:447–453
  9. Rutqvist LE , Lax I , Fornander T , et al.   Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer . Int J Radiat Oncol Biol Phys . 1992;22:887–896
  10. Stewart JR , Fajardo LF , Gillette SM , et al.   Radiation injury to the heart . Int J Radiat Oncol Biol Phys . 1995;31:1205–1211
  11. Haybittle JL , Brinkley D , Houghton J , et al.   Postoperative radiotherapy and late mortality (Evidence from the Cancer Research Campaign Trial for early breast cancer) . Br Med J . 1989;298:1611–1614
  12. Host H , Brennhovd IO , Lock M . Post operative radiotherapy in breast cancer long-term results from the Oslo Study . Int J Radiat Oncol Biol Phys . 1986;12:727–732
  13. Hancock SL , Tucker MA , Hoppe RT . Factors affecting late mortality from heart disease after treatment of Hodgkin’s Disease . JAMA . 1993;270:1949–1955
  14. Harris JR , Hellman S . Put the “Hockey stick” on ice . Int J Radiat Oncol Biol Phys . 1988;15:497–499
  15. Seddon BM , Cook A , Gothard L , et al.   Detection of coronary and myocardial disease in patients with early breast cancer treated with radiotherapy [Abstract] . Progr Proceed Am Soc Clin Oncol . 2001;20:29a
  16. Shapiro CL , Hardenbergh PH , Gelman R , et al.   Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients . J Clin Oncol . 1998;16:3493–3501
  17. Valagussa P , Zambetti M , Biasi S , et al.   Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancer . Ann Oncol . 1994;5:209–216
  18. Von Hoff DD , Layard MW , Basa P , et al.   Risk failures for doxorubicin-induced congestive heart failure . Ann Intern Med . 1977;91:710–711
  19. Billingham ME , Briston MR , Glabstein  , et al.   Adriamycin cardiotoxicity (Endomyocardial biopsy evidence of enhancement by irradiation) . Am J Surg Pathol . 1977;1:17–23
  20. Eltringham JR , Fajardo L , Stewart JR , et al.   Investigation of cardiotoxicity in rabbits from adriamycin and fractionated cardiac irradiation (Preliminary result) . Front Radiat Ther Oncol . 1979;13:21–35
  21. Lipshultz S , Colan S , Gelber R , et al.   Late effects of doxorubicin therapy for ALL in childhood . N Engl J Med . 1991;324:808–815
  22. Gustavsson A , Bendahl P , Cwikiel M , et al.   No serious late cardiac effects after adjuvant radiotherapy following mastectomy in premenopausal women with early breast cancer . Int J Radiat Oncol Biol Phys . 1999;43:745–754
  23. Gyenes G , Fornander T , Carlens P , et al.   Morbidity of ischemic heart disease in early stage breast cancer 15–20 years after adjuvant radiotherapy . Int J Radiat Oncol Biol Phys . 1994;28:1235–1241
  24. Sailer SL , Chaney EL , Rosenman JG , et al.   Treatment planning at the University of North Carolina at Chapel Hill . Semin Radiat Oncol . 1992;2:267–273
  25. Hardenbergh PH , Munley MT , Bentel GC , et al.   Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin (Preliminary results) . Int J Radiat Oncol Biol Phys . 2001;49:1023–1028
  26. Sherouse GW , Bourland JD , Reynolds KL , et al.   Virtual simulation in the clinical setting (Some practical considerations) . Int J Radiat Oncol Biol Phys . 1990;19:1059–1065
  27. Borges-Neto S , Coleman RE , Jones RH . Perfusion and function at rest and treadmill using technetium-99m sestamibi (Comparison of one and two day protocols in normal volunteers) . J Nucl Med . 1990;31:1128–1132
  28. Borges-Neto S , Shaw LJ , Kesler KL , et al.   Prediction of severe coronary artery disease by combined rest and exercise radionuclide angiocardiography and tomographic perfusion imaging with technetium-99m labeled sestamibi (A comparison with clinical and electrocardiographic data) . J Nucl Cardiol . 1997;4:189–194
  29. Jones RH , Borges-Neto S , Potts JM . Simultaneous measurement of myocardial perfusion and ventricular function during exercise from a single injection of technetium-99m sestamibi in coronary artery disease . Am J Cardiol . 1990;66:68E–71E
  30. Hachamovitch R , Berman DS , Kiat H , et al.   Exercise myocardial perfusion SPECT in patients without known coronary artery disease (Incremental prognostic value and impact on subsequent patient management) . Circulation . 1996;93:905–914
  31. Mast ST , Shaw LK , Ravizzini GC , et al.   Incremental prognostic value of RNA ejection fraction measurements during pharmacologic stress testing (A comparison with clinical and perfusion variables) . J Nucl Med . 2001;42:871–877
  32. Borges-Neto S, Shaw LK, Alexander JH, et al. Incremental prognostic power of SPECT imaging in patients with documented or high risk coronary artery disease. Radiology. In press.
  33. Germano G , Kiat H , Kavanaugh PB , et al.   Automatic quantification of ejection fraction from gated myocardial perfusion SPECT . J Nucl Med . 1995;36:2138–2147
  34. Agresti A . Categorical data analysis . New York: John Wiley & Sons; 1990;
  35. Hojris I , Ronnow Sand NP , Andersen J , et al.   Myocardial perfusion imaging in breast cancer patients treated with or without post-mastectomy radiotherapy . Radiother Oncol . 2000;55:163–172
  36. Cowen D , Gonzague-Casabianca L , Brenot-Rossi I , et al.   Thallium-201 perfusion scintigraphy in left-side breast cancer treated with adjuvant radiotherapy . Int J Radiat Oncol Biol Phys . 1998;41:809–815
  37. Seddon B , Cook A , Gothard L , et al.   Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy . Radiother Oncol . 2002;64:53–63
  38. Gyenes G , Forander T , Carlens P , et al.   Myocardial damage in breast cancer patients treated with adjuvant radiotherapy (A prospective study) . Int J Radiat Oncol Biol Phys . 1996;36:899–905
  39. Borges-Neto S , Coleman RE , Potts JM , et al.   Combined exercise radionuclide angiocardiography and single photon emission computed tomography perfusion studies for assessment of coronary artery disease . Semin Nucl Med . 1991;21:223–229
  40. Yu XL , Prosnitz RR , Zhou SM , et al.   Symptomatic “cardiac” events following radiation therapy (RT) for left-sided breast cancer (Possible association with RT-induced changes in regional perfusion) . Clin Breast Cancer . 2003;4:193–197
  41. Lind PA , Pagnanelli R , Marks LB , et al.   Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution . Int J Radiat Oncol Biol Phys . 2003;55:914–920
  42. Otto CM . The practice of clinical echocardiography . 2nd ed. Philadelphia: W.B. Saunders; 2002;
  43. Choragudi NL , Prakash AM , Sun Y , et al.   Comparison of echocardiography with technetium 99m-gated single photon emission computed tomography as diagnostic tools for left ventricular ejection fraction . Echocardiography . 2001;18:627–632
  44. Marks LB , Hebert ME , Bentel G , et al.   To treat or not to treat the internal mammary nodes (A possible compromise) . Int J Radiat Oncol Biol Phys . 1994;29:903–909
  45. Quaranta BP , Prosnitz R , Steffey B , et al.   Customized blocking of tangential radiation (RT) breast fields: Excluding the heart vs. covering the breast. Striking a balance . [Abstract] Breast Cancer Res Treat . 2002;76(Suppl. 1):S118
  46. Hurkmans CW , Cho BC , Damen E , et al.   Reduction of cardiac and lung complication probabilities after breast irradiation using conformal radiotherapy with or without intensity modulation . Radiother Oncol . 2002;62:163–171
  47. Marks LB , Yu XL , Zhou SM , et al.   The impact of irradiated left ventricular volume on the incidence of radiation-induced cardiac perfusion changes [Abstract] . Int J Radiat Oncol Biol Phys . 2003;57:S129
  48. Chui CS , Hong L , Hunt M , et al.   A simplified intensity modulated radiation therapy technique for the breast . Med Phys . 2002;29:522–529
  49. Vicini FA , Sharpe M , Kestin L , et al.   Optimizing breast cancer treatment efficacy with intensity-modulated radiotherapy . Int J Radiat Oncol Biol Phys . 2002;54:1336–1344
  50. Lo YC , Yasuda G , Fitzgerald TJ , et al.   Intensity modulation for breast treatment using static multi-leaf collimators . Int J Radiat Oncol Biol Phys . 2002;46:187–194
  51. Chang SX , Deschesne KM , Cullip TJ , et al.   A comparison of different intensity modulation treatment techniques for tangential breast irradiation . Int J Radiat Oncol Biol Phys . 1999;45:1305–1314
  52. Hong L , Hunt M , Chui C , et al.   Intensity-modulated tangential beam irradiation of the intact breast . Int J Radiat Oncol Biol Phys . 1999;44:1155–1164
  53. Remouchamps VM , Letts N , Vicini FA , et al.   Initial clinical experience with moderate deep-inspiration breath hold using an active breathing control device in the treatment of patients with left-sided breast cancer using external beam radiation therapy . Int J Radiat Oncol Biol Phys . 2003;56:704–715
  54. Remouchamps VM , Vicini FA , Sharpe MB , et al.   Significant reductions in heart and lung doses using deep inspiration breath hold with active breathing control and intensity-modulated radiation therapy for patients treated with locoregional breast irradiation . Int J Radiat Oncol Biol Phys . 2003;55:392–406
  55. Sixel KE , Aznar MC , Ung YC . Deep inspiration breath hold to reduce irradiated heart volume in breast cancer patients . Int J Radiat Oncol Biol Phys . 2001;49:199–204
  56. Lu HM , Cash E , Chen MH , et al.   Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers (A CT study) . Int J Radiat Oncol Biol Phys . 2000;47:895–904
  57. Fowble B , Hanlon A , Freedman G , et al.   Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer . Int J Radiat Oncol Biol Phys . 2000;47:883–894
  58. Obedian E , Haffty BG . Internal mammary nodal irradiation in conservatively-managed breast cancer patients (Is there a benefit?) . Int J Radiat Oncol Biol Phys . 1999;44:997–1003
  59. Stemmer SM , Rizel S , Hardan I , et al.   The role of irradiation of the internal mammary lymph nodes in high-risk stage II to IIIA breast cancer patients after high-dose chemotherapy (A prospective sequential nonrandomized study) . J Clin Oncol . 2003;21:2713–2718
  60. Bentel G , Marks LB , Hardenbergh P , et al.   Variability of the location of internal mammary vessels and glandular breast tissue in breast cancer patients undergoing routine CT-based treatment planning . Int J Radiat Oncol Biol Phys . 1999;44:1017–1025
  61. Vicini FA , Kestin L , Chen P , et al.   Limited-field radiation therapy in the management of early-stage breast cancer . J Natl Cancer Inst . 2003;95:1205–1210
  62. King TA , Bolton JS , Kuske RR , et al.   Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer . Am J Surg . 2000;180:299–304
  63. Veronesi U , Orecchia R , Luini A , et al.   A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated . Eur J Cancer . 2001;37:2178–2183

 Supported in part by Grants 17-98-1-8071 and BC010663 from the Department of Defense.Dr. P. H. Hardenbergh’s current address is Vale Medical Center, Vale, CO.

PII: S0360-3016(05)00157-4

doi: 10.1016/j.ijrobp.2005.01.029

International Journal of Radiation Oncology * Biology * Physics
Volume 63, Issue 1 , Pages 214-223 , 1 September 2005