With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data.

Department of Oncology and Radiotherapy University Hospital Hradec Kralove Czech Republic

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Gupta B., Kumar N. Worldwide incidence, mortality and time trends for cancer of the oesophagus. Eur J Cancer Prev. 2017;26:107–118. PubMed

Wong M.C.S., Hamilton W., Whiteman D.C. Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries. Sci Rep. 2018;8:4522. PubMed PMC

Xie S.H., Lagergren J. Risk factors for oesophageal cancer. Best Pract Res Clin Gastroenterol. 2018;36–37:3–8. PubMed

Thrift A.P., Whiteman D.C. The incidence of esophageal adenocarcinoma continues to rise: Analysis of period and birth cohort effects on recent trends. Ann Oncol. 2012;23:3155–3162. PubMed

Malhotra G.K., Yanala U., Ravipati A., Follet M., Vijayakumar M., Are C. Global trends in esophageal cancer. J Surg Oncol. 2017;115:564–579. PubMed

Lordick F., Mariette C., Haustermans K., Obermannová R., Arnold D., ESMO Guidelines Committee Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v50–v57. PubMed

The National Comprehensive Cancer Network (NCCN). Esophageal and Esophagogastric Junction Cancer. Version 1.2019. https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf [accessed 23 April 2019].

Cooper J.S., Guo M.D., Herskovic A. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999;281:1623–1627. PubMed

Minsky B.D., Pajak T.F., Ginsberg R.J. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20:1167–1174. PubMed

Ruppert B.N., Watkins J.M., Shirai K. Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer. Am J Clin Oncol. 2010;33:346–352. PubMed

Conroy T., Galais M.P., Raoul J.L. Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014;15:305–314. PubMed

Urschel J.D., Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg. 2003;185:538–543. PubMed

Fiorica F., Di Bona D., Schepis F. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53:925–930. PubMed PMC

Shapiro J., van Lanschot J.J., Hulshof M.C. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16:1090–1098. PubMed

ICRU; Bethesda, MD: 1993. International commission on radiation units and measurements (ICRU). prescribing, recording, and reporting photon beam therapy. ICRU report 50.

ICRU; Bethesda, MD: 1999. International Commission on Radiation Units and Measurements. ICRU Report 62: Prescribing, recording, and reporting photon beam therapy (supplement to ICRU Report 50)

Han D., Yuan Y., Song X., Yu Y., Yu J. What is the appropriate clinical target volume for esophageal squamous cell carcinoma? Debate and consensus based on pathological and clinical outcomes. J Cancer. 2016;7:200–206. PubMed PMC

Dong Y., Guan H., Huang W. Precise delineation of clinical target volume for crossing-segments thoracic esophageal squamous cell carcinoma based on the pattern of lymph node metastases. J Thorac Dis. 2015;7(Dec (12)):2313–2320. PubMed PMC

Vosmik M., Petera J., Sirak I. Technological advances in radiotherapy for esophageal cancer. World J Gastroenterol. 2010;16:5555–5564. PubMed PMC

Vieillevigne L., Vidal M., Izar F., Rives M. Is dose escalation achievable for esophageal carcinoma? Rep Pract Oncol Radiother. 2015;20(Jan 5(2)):135–140. PubMed PMC

Darby S.C., Ewertz M., McGale P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987–998. PubMed

van den Bogaard V.A., Ta B.D., van der Schaaf A. Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures. J Clin Oncol. 2017;35:1171–1178. PubMed PMC

Hahn E., Jiang H., Ng A. Late cardiac toxicity after mediastinal radiation therapy for Hodgkin lymphoma: contributions of coronary artery and whole heart dose-volume variables to risk prediction. Int J Radiat Oncol Biol Phys. 2017;98:1116–1123. PubMed

van Nimwegen F.A., Schaapveld M., Cutter D.J. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin Lymphoma. J Clin Oncol. 2016;34:235–243. PubMed

Mathieu L.N., Kanarek N.F., Tsai H.L., Rudin C.M., Brock M.V. Age and sex differences in the incidence of esophageal adenocarcinoma: results from the Surveillance, Epidemiology, and End Results (SEER) Registry (1973–2008) Dis Esophagus. 2014;27:757–763. PubMed PMC

Wang Q.L., Xie S.H., Wahlin K., Lagergren J. Global time trends in the incidence of esophageal squamous cell carcinoma. Clin Epidemiol. 2018;10:717–728. PubMed PMC

Worni M., Castleberry A.W., Gloor B. Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008. Dis Esophagus. 2014;27:662–669. PubMed PMC

Sio T.T., Wilson Z.C., Stauder M.C. Long-term treatment outcomes for locally advanced esophageal cancer: a single-institution experience. Am J Clin Oncol. 2016;39:448–452. PubMed

Fakhrian K., Ordu A.D., Lordick F. Long-term outcomes of trimodality treatment for squamous cell carcinoma of the esophagus with cisplatin and/or 5-FU: more than 20 years’ experience at a single institution. Strahlenther Onkol. 2014;190:1133–1140. PubMed

van Hagen P., Hulshof M.C., van Lanschot J.J. CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–2084. PubMed

Yusuf S.W., Venkatesulu B.P., Mahadevan L.S., Krishnan S. Radiation-induced cardiovascular disease: a clinical perspective. Front Cardiovasc Med. 2017;4:66. PubMed PMC

Spetz J., Moslehi J., Sarosiek K. Radiation-induced cardiovascular toxicity: mechanisms, prevention, and treatment. Curr Treat Options Cardiovasc Med. 2018;20:31. PubMed PMC

Gharzai L., Verma V., Denniston K.A., Bhirud A.R., Bennion N.R., Lin C. 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 PubMed PMC

Frandsen J., Boothe D., Gaffney D.K., Wilson B.D., Lloyd S. Increased risk of death due to heart disease after radiotherapy for esophageal cancer. J Gastrointest Oncol. 2015;6:516–523. PubMed PMC

Beukema J.C., van Luijk P., Widder J., Langendijk J.A., Muijs C.T. Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer. Radiother Oncol. 2015;114:85–90. PubMed

Ogino I., Watanabe S., Iwahashi N. Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer. Strahlenther Onkol. 2016;192:359–367. PubMed

Wei X., Liu H.H., Tucker S.L. Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2008;70:707–714. PubMed

Fukada J., Shigematsu N., Takeuchi H. Symptomatic pericardial effusion after chemoradiation therapy in esophageal cancer patients. Int J Radiat Oncol Biol Phys. 2013;87:487–493. PubMed

Ishikura S., Nihei K., Ohtsu A. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003;21:2697–2702. PubMed

Ogino I., Watanabe S., Sakamaki K., Ogino Y., Kunisaki C., Kimura K. Dosimetric predictors of radiation-induced pericardial effusion in esophageal cancer. Strahlenther Onkol. 2017;193:552–560. PubMed

Konski A., Li T., Christensen M. Symptomatic cardiac toxicity is predicted by dosimetric and patient factors rather than changes in 18F-FDG PET determination of myocardial activity after chemoradiotherapy for esophageal cancer. Radiother Oncol. 2012;104:72–77. PubMed PMC

Tait L.M., Meyer J.E., McSpadden E. Women at increased risk for cardiac toxicity following chemoradiation therapy for esophageal carcinoma. Pract Radiat Oncol. 2013;3:e149–55. PubMed

Lester S.C., Lin S.H., Chuong M. A multi-institutional analysis of trimodality therapy for esophageal cancer in elderly patients. Int J Radiat Oncol Biol Phys. 2017;98:820–828. PubMed

Hayashi Y., Iijima H., Isohashi F. The heart’s exposure to radiation increases the risk of cardiac toxicity after chemoradiotherapy for superficial esophageal cancer: a retrospective cohort study. BMC Cancer. 2019;19:195. PubMed PMC

Sekii S., Ito Y., Harada K. Intrafraction esophageal motion in patients with clinical T1N0 esophageal cancer. Rep Pract Oncol Radiother. 2018;23:398–401. PubMed PMC

Chen Y.J., Liu A., Han C. Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution. Med Dosim. 2007;32:166–171. PubMed

Choi K.H., Kim J., Lee S.W., Kang Y.N., Jang H. Dosimetric comparison between modulated arc therapy and static intensity modulated radiotherapy in thoracic esophageal cancer: a single institutional experience. Radiat Oncol J. 2018;36:63–70. PubMed PMC

Kataria T., Govardhan H.B., Gupta D. Dosimetric comparison between volumetric modulated arc therapy (VMAT) vs intensity modulated radiation therapy (IMRT) for radiotherapy of mid esophageal carcinoma. J Cancer Res Ther. 2014;10:871–877. PubMed

Wu Z., Xie C., Hu M. Dosimetric benefits of IMRT and VMAT in the treatment of middle thoracic esophageal cancer: is the conformal radiotherapy still an alternative option? J Appl Clin Med Phys. 2014;15:93–101. PubMed PMC

Xu C., Xi M., Komaki R. Dosimetric and clinical outcomes after volumetric modulated arc therapy for carcinoma of the thoracic esophagus. Adv Radiat Oncol. 2017;2:325–332. PubMed PMC

Hirano Y., Onozawa M., Hojo H. Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma. Radiat Oncol. 2018;13:23. PubMed PMC

Ling T.C., Slater J.M., Nookala P. 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;6:2356–2368. PubMed PMC

Shiraishi Y., Xu C., Yang J., Komaki R., Lin S.H. Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy. Radiother Oncol. 2017;125:48–54. PubMed

Prayongrat A., Xu C., Li H., Lin S.H. Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. Adv Radiat Oncol. 2017;2:301–307. PubMed PMC

Venkat P.S., Shridhar R., Naghavi A.O. Dose escalated neoadjuvant chemoradiotherapy with dose-painting intensity-modulated radiation therapy and improved pathologic complete response in locally advanced esophageal cancer. Dis Esophagus. 2017;30:1–9. PubMed