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Radiation-induced heart disease after treatment for esophageal cancer

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Abstract

Recently, the development of radiotherapy technology and to radiation-induced heart disease in patients with esophageal cancer. Investigations using chemotherapy has improved treatment results for esophageal cancer, and attention has been paidSEER for esophageal cancer showed that the hazard ratio of heart-related death was 1.62–1.96. Herein we review published literature regarding the mechanism of and countermeasures for radiation-induced heart disease and discuss the potential of concurrent chemotherapy, molecular-targeted agents and lifestyle for exacerbating radiation-induced heart disease.

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References

  1. Ariga H, Nemoto K, Miyazaki S, et al. Prospective comparison of surgery alone and chemoradiotherapy with selective surgery in resectable squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys. 2009;75(2):348–56.

    Article  PubMed  Google Scholar 

  2. Pöttgen C, Stuschke M. Radiotherapy versus surgery within multimodality protocols for esophageal cancer—a meta-analysis of the randomized trials. Cancer Treat Rev. 2012;38:599–604.

    Article  PubMed  Google Scholar 

  3. Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006;24:4107.

    Article  CAS  PubMed  Google Scholar 

  4. Aleman BMP, van den Belt-Dusebout AW, Klokman WJ, et al. Long-term cause-specific mortality of patients treated for Hodgkin’s disease. J Clin Oncol. 2003;21:3431–9.

    Article  PubMed  Google Scholar 

  5. Ozasa K, Takahashi I, Grant EJ. Radiation-related risks of non-cancer outcomes in the atomic bomb survivors. Ann ICRP. 2016;45(1 Suppl):253–61.

    Article  CAS  PubMed  Google Scholar 

  6. Jingu K, Matsushita H, Takeda K, et al. Results of chemoradiotherapy for stage I esophageal cancer in medically inoperable patients compared with results in operable patients. Dis Esophagus. 2013;26(5):522–7.

    Article  CAS  PubMed  Google Scholar 

  7. Jingu K, Umezawa R, Matsushita H, et al. Chemoradiotherapy for T4 and/or M1 lymph node esophageal cancer: experience since 2000 at a high-volume center in Japan. Int J Clin Oncol. 2016;21(2):276–82.

    Article  CAS  PubMed  Google Scholar 

  8. Umezawa R, Jingu K, Matsushita H, et al. Long-term results of chemoradiotherapy for stage II–III thoracic esophageal cancer in a single institution after 2000—with a focus on comparison of three protocols. BMC Cancer. 2015;15:813.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Nishimura Y, Jingu K, Itasaka S, et al. Clinical outcomes of radiotherapy for esophageal cancer between 2004 and 2008: the second survey of the Japanese Radiation Oncology Study Group (JROSG). Int J Clin Oncol. 2016;21(1):88–94.

    Article  PubMed  Google Scholar 

  10. Yamada S, Nemoto K, Takai Y, et al. Proposal for standard radiotherapy methods for superficial esophageal cancer: a multicenter retrospective evaluation. J JASTRO. 2000;12:169–76.

    Google Scholar 

  11. Ishikura S, Nihei K, Ohtsu A, et al. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003;21(14):2697–702.

    Article  CAS  PubMed  Google Scholar 

  12. Frandsen J, Boothe D, Gaffney DK, et al. Increased risk of death due to heart disease after radiotherapy for esophageal cancer. J Gastrointest Oncol. 2015;6:516–23.

    PubMed  PubMed Central  Google Scholar 

  13. Gharzai L, Verma V, Denniston KA, et al. Radiation therapy and cardiac death in long-term survivors of esophageal cancer: an analysis of the surveillance, epidemiology, and end result database. PLoS One. 2016;11(7):e0158916.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2768–801.

    Article  PubMed  Google Scholar 

  15. Veinot JP, Edwards WD. Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases. Hum Pathol. 1996;27(8):766–73.

    Article  CAS  PubMed  Google Scholar 

  16. Darby SC, Cutter DJ, Boerma M, et al. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010;76:656–65.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Carmel RJ, Kaplan HS. Mantle irradiation in Hodgkin’s disease. An analysis of technique, tumour eradication, and complications. Cancer. 1976;37:2813–25.

    Article  CAS  PubMed  Google Scholar 

  18. Karram T, Rinkevitch D, Markiewicz W. Poor outcome in radiation-induced constrictive pericarditis. Int J Radiat Oncol Biol Phys. 1993;25(2):329–31.

    Article  CAS  PubMed  Google Scholar 

  19. Wei X, Liu HH, Tucker SL, et al. Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2008;70:707–14.

    Article  PubMed  Google Scholar 

  20. Tamari K, Isohashi F, Akino Y, et al. Risk factors for pericardial effusion in patients with stage I esophageal cancer treated with chemoradiotherapy. Anticancer Res. 2014;34(12):7389–93.

    PubMed  Google Scholar 

  21. Fukuda J, Shigematsu N, Takeuchi H, et al. Symptomatic pericardial effusion after chemoradiation therapy in esophageal cancer patients. Int J Radiat Oncol Biol Phys. 2013;87(3):487–93.

    Article  PubMed  Google Scholar 

  22. Nishizawa S, Nakamura T, Shiraishi H, et al. Successful treatment with low dose steroids for recurrent radiation pericarditis after chemoradiotherapy of lower esophageal cancer: a case report. Heart 2010;42:369–374 (Japanese).

  23. Nishimura Y, Hiraoka M, Koike R, et al. Long-term follow-up of a randomized Phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021). Jpn J Clin Oncol. 2012;42(9):807–12.

    Article  PubMed  Google Scholar 

  24. Gladstone DJ, Flanagan MF, Southworth JB, et al. Radiation-induced cardiomyopathy as a function of radiation beam gating to the cardiac cycle. Phys Med Biol. 2004;49:1475–84.

    Article  PubMed  Google Scholar 

  25. Weintraub NL, Jones WK, Manka D. Understanding radiation-induced vascular disease. J Am Coll Cardiol. 2010;55(12):1237–9.

    Article  CAS  PubMed  Google Scholar 

  26. 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(1):53–63.

    Article  PubMed  Google Scholar 

  27. Umezawa R, Takase K, Jingu K, et al. Evaluation of radiation-induced myocardial damage using iodine-123 β-methyl-iodophenyl pentadecanoic acid scintigraphy. J Radiat Res. 2013;54(5):880–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Umezawa R, Takanami K, Kadoya N, et al. Assessment of myocardial metabolic disorder associated with mediastinal radiotherapy for esophageal cancer -a pilot study. Radiat Oncol. 2015;10(1):96.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gyenes G, Rutqvist LE, Liedberg A, Fornander T. 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. 1998;48(2):185–90.

    Article  CAS  PubMed  Google Scholar 

  30. Ling TC, Slater JM, Nookala P, et al. Analysis of intensity-modulated radiation therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) for reducing perioperative cardiopulmonary complications in esophageal cancer patients. Cancers (Basel). 2014;6(4):2356–68.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Jingu K, Nemoto K, Kaneta T, et al. Temporal change in brain natriuretic Peptide after radiotherapy for thoracic esophageal cancer. Int J Radiat Oncol Biol Phys. 2007;69(5):1417–23.

    Article  CAS  PubMed  Google Scholar 

  32. Palumbo I, Palumbo B, Fravolini ML, et al. Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: a prospective study. Breast. 2016;25:45–50.

    Article  CAS  PubMed  Google Scholar 

  33. van der Veen SJ, Ghobadi G, de Boer RA, et al. ACE inhibition attenuates radiation-induced cardiopulmonary damage. Radiother Oncol. 2015;114(1):96–103.

    Article  PubMed  Google Scholar 

  34. Brosius FC 3rd, Waller BF, Roberts WC. Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med. 1981;70:519–30.

    Article  PubMed  Google Scholar 

  35. Heidenreich PA, Hancock SL, Lee BK, et al. Asymptomatic cardiac disease following mediastinal irradiation. J Am Coll Cardiol. 2003;42(4):743–9.

    Article  PubMed  Google Scholar 

  36. Malanca M, Cimadevilla C, Brochet E, et al. Radiotherapy-induced mitral stenosis: a three-dimensional perspective. J Am Soc Echocardiogr 2010;23:108.e1–2.

  37. Copeland KA, Hosmane VR, Jurkovitz C, et al. Frequency of severe valvular disease caused by mediastinal radiation among patients undergoing valve surgery in a community-based, regional academic medical center. Clin Cardiol. 2013;36(4):217–21.

    Article  PubMed  Google Scholar 

  38. Baeuml H, Behrends U, Peter RU, et al. Ionizing radiation induces, via generation of reactive oxygen intermediates, intercellular adhesion molecule-1 (ICAM-1) gene transcription and NF kappa B-like binding activity in the ICAM-1 transcriptional regulatory region. Free Radic Res. 1997;27:127–42.

    Article  CAS  PubMed  Google Scholar 

  39. Gyenes G, Fornander T, Carlens P, et al. Detection of radiation-induced myocardial damage by technetium-99m sestamibi scintigraphy. Eur J Nucl Med. 1997;24:286–92.

    CAS  PubMed  Google Scholar 

  40. Küpeli S, Hazirolan T, Varan A, et al. Evaluation of coronary artery disease by computed tomography angiography in patients treated for childhood Hodgkin’s lymphoma. J Clin Oncol. 2010;28(6):1025–30.

    Article  PubMed  Google Scholar 

  41. Kaplan BM, Miller AJ, Bharati S, et al. Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature. Arch Intern Med. 1981;141:676–9.

    Article  Google Scholar 

  42. Tötterman KJ, Pesonen E, Siltanen P. Radiation-related chronic heart disease. Chest. 1983;83(6):875–8.

    Article  PubMed  Google Scholar 

  43. Slama MS, Le Guludec D, Sebag C, et al. Complete atrioventricular block following mediastinal irradiation: a report of six cases. Pacing Clin Electrophysiol. 1991;14(7):1112–8.

    Article  CAS  PubMed  Google Scholar 

  44. Pohjola-Sintonen S, Tötterman KJ, Kupari M. Sick sinus syndrome as a complication of mediastinal radiation therapy. Cancer. 1990;65:2494–6.

    Article  CAS  PubMed  Google Scholar 

  45. Zuppinger C, Timolati F, Suter TM. Pathophysiology and diagnosis of cancer drug induced cardiomyopathy. Cardiovasc Toxicol. 2007;7(2):61–6.

    Article  CAS  PubMed  Google Scholar 

  46. Floyd JD, Nguyen DT, Lobins RL, et al. Cardiotoxicity of cancer therapy. J Clin Oncol. 2005;23(30):7685–96.

    Article  CAS  PubMed  Google Scholar 

  47. Lieutaud T, Brain E, Golgran-Toledano D, et al. 5-Fluorouracil cardiotoxicity: a unique mechanism for ischaemic cardiopathy and cardiac failure? Eur J Cancer 1996; 32a:368–9.

  48. Chirino J, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 2009;61:223–42.

  49. Suter TM, Ewer MS. Cancer drugs and the heart: importance and management. Eur Heart J. 2013;34(15):1102–11.

    Article  CAS  PubMed  Google Scholar 

  50. Zhang W, Zhao L, Liu J, et al. Cisplatin induces platelet apoptosis through the ERK signaling pathway. Thromb Res. 2012;130(1):81–91.

    Article  CAS  PubMed  Google Scholar 

  51. Saito K, Takeda K, Yoshida K, et al. Assessment of fatty acid metabolism in taxan-induced myocardial damage with iodine-123 BMIPP SPECT: comparative study with myocardial perfusion, left ventricular function, and histopathological findings. Ann Nucl Med. 2003;17(6):481–8.

    Article  CAS  PubMed  Google Scholar 

  52. Tomonari M, To H, Nishida M, Mishima T, Sasaki H, Kurose H. Mechanism of the cardioprotective effects of docetaxel pre-administration against adriamycin-induced cardiotoxicity. J Pharmacol Sci. 2011;115(3):336–45.

    Article  CAS  PubMed  Google Scholar 

  53. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.

    Article  CAS  PubMed  Google Scholar 

  54. Marinko T, Dolenc J, Bilban-Jakopin C. Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. Radiol Oncol. 2014;48(2):105–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Friess H, Fukuda A, Tang WH, et al. Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer: overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3. World J Surg. 1999;23:1010–8.

    Article  CAS  PubMed  Google Scholar 

  56. Cellini F, Valentini V. Targeted therapies in combination with radiotherapy in oesophageal and gastroesophageal carcinoma. Curr Med Chem. 2014;21(8):990–1004.

    Article  CAS  PubMed  Google Scholar 

  57. Ikushima H, Takegawa Y, Yasuda H, et al. Radiation complications following breast conserving therapy. Breast Cancer. 1998;5(4):395–400.

    Article  CAS  PubMed  Google Scholar 

  58. Dorth JA, Patel PR, Broadwater G, et al. Incidence and risk factors of significant carotid artery stenosis in asymptomatic survivors of head and neck cancer after radiotherapy. Head Neck. 2014;36(2):215–9.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-chou, Aoba-ku, Sendai, 980-8574, Japan

    Keiichi Jingu, Rei Umezawa & Katsuya Fukui

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  1. Keiichi Jingu
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  2. Rei Umezawa
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  3. Katsuya Fukui
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Correspondence to Keiichi Jingu.

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This article is a review. It did not involve any new clinical or laboratory work by the authors. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the principles of the Declaration of Helsinki (2013).

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Jingu, K., Umezawa, R. & Fukui, K. Radiation-induced heart disease after treatment for esophageal cancer. Esophagus 14, 215–220 (2017). https://doi.org/10.1007/s10388-017-0569-5

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