AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision‐making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer.
A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5‐ and 10‐year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C‐index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan‐Meier (K‐M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five‐ and ten‐year survival rates for the two groups were shown using K‐M curves.
The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C‐indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5‐ and 10‐year risk of cardiac death. The model exhibited moderate predictive power for 5‐ and 10‐year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively).
Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660
Xie SH, Wahlin K, Lagergren J. Cause of death in patients diagnosed with esophageal cancer in Sweden: a population‐based study. Oncotarget. 2017;8(31):51800–9. https://doi.org/10.18632/oncotarget.15270
Deng W, Yu R, Yang Z, Dong X, Wang W. Trends in conditional overall survival of esophageal cancer: a population‐based study. Ann Transl Med. 2021;9(2):102. https://doi.org/10.21037/atm-20-2798
He SM, Xu J, Liu XJ, Zhen YS. Advances and challenges in the treatment of esophageal cancer. Acta Pharm Sin B. 2021;11(11):3379–92. https://doi.org/10.1016/j.apsb.2021.03.008
Qi L, Luo Q, Zhang Y, Jia F, Zhao Y, Wang F. Advances in toxicological research of the anticancer drug cisplatin. Chem Res Toxicol. 2019;32(8):1469–86. https://doi.org/10.1021/acs.chemrestox.9b00204
Brell JM. 5‐Fluorouracil cardiotoxicity: known but unknown. JACC: CardioOncol. 2021;3(1):110–2. https://doi.org/10.1016/j.jaccao.2021.01.006
Lu YJ, Deng SZ, Dou QY, Pan W, Liu QQ, Ji HC, et al. Treatment‐related coronary disorders of fluoropyrimidine administration: a systematic review and meta‐analysis. Front Pharmacol. 2022;13:885699. https://doi.org/10.3389/fphar.2022.885699
Moriyama S, Yokoyama T, Irie K, Ito M, Tsuchihashi K, Fukata M, et al. Atrial fibrillation observed in a patient with esophageal cancer treated with fluorouracil. J Cardiol Cases. 2019;20(5):183–6. https://doi.org/10.1016/j.jccase.2019.08.005
Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxorubicin‐induced cardiotoxicity: an update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother. 2021;139:111708. https://doi.org/10.1016/j.biopha.2021.111708
Stein‐Merlob AF, Rothberg MV, Ribas A, Yang EH. Cardiotoxicities of novel cancer immunotherapies. Heart. 2021;107(21):1694–703. https://doi.org/10.1136/heartjnl-2020-318083
Yang YM, Hong P, Xu WW, He QY, Li B. Advances in targeted therapy for esophageal cancer. Signal Transduct Target Ther. 2020;5(1):229. https://doi.org/10.1038/s41392-020-00323-3
Vošmik M, Hodek M, Buka D, Sýkorová P, Grepl J, Paluska P, et al. Cardiotoxicity of radiation therapy in esophageal cancer. Rep Pract Oncol Radiother. 2020;25(3):318–22. https://doi.org/10.1016/j.rpor.2020.02.005
Beukema JC, van Luijk P, Widder J, Langendijk JA, Muijs CT. Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer? Radiother Oncol. 2015;114(1):85–90. https://doi.org/10.1016/j.radonc.2014.11.037
Wang X, Palaskas NL, Hobbs BP, Abe JI, Nead KT, et al. The impact of radiation dose to heart substructures on major coronary events and patient survival after chemoradiation therapy for esophageal. Cancers. 2022;14(5):1304. https://doi.org/10.3390/cancers14051304
Ell P, Martin JM, Cehic DA, Ngo DTM, Sverdlov AL. Cardiotoxicity of radiation therapy: mechanisms, management, and mitigation. Curr Treat Options Oncol. 2021;22(8):70. https://doi.org/10.1007/s11864-021-00868-7
Garant A, Spears G, Routman D, Whitaker T, Liao Z, Harmsen W, et al. A multi‐institutional analysis of radiation dosimetric predictors of toxicity after trimodality therapy for esophageal cancer. Pract Radiat Oncol. 2021;11(4):e415–e425. https://doi.org/10.1016/j.prro.2021.01.004
Ogino I, Watanabe S, Iwahashi N, Kosuge M, Sakamaki K, Kunisaki C, et al. Symptomatic radiation‐induced cardiac disease in long‐term survivors of esophageal cancer. Strahlenther Onkol. 2016;192(6):359–67. https://doi.org/10.1007/s00066-016-0956-1
Ishikura S, Nihei K, Ohtsu A, Boku N, Hironaka S, Mera K, et al. Long‐term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003;21(14):2697–702. https://doi.org/10.1200/jco.2003.03.055
Lester SC, Lin SH, Chuong M, Bhooshan N, Liao Z, Arnett AL, et al. A multi‐institutional analysis of trimodality therapy for esophageal cancer in elderly patients. Int J Radiat Oncol Biol Phys. 2017;98(4):820–8. https://doi.org/10.1016/j.ijrobp.2017.02.021
Hayashi Y, Iijima H, Isohashi F, Tsujii Y, Fujinaga T, Nagai K, et al. 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(1):195. https://doi.org/10.1186/s12885-019-5421-y
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(7):552–60. https://doi.org/10.1007/s00066-017-1127-8
Wei X, Liu HH, Tucker SL, Wang S, Mohan R, Cox JD, 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(3):707–14. https://doi.org/10.1016/j.ijrobp.2007.10.056
Frandsen J, Boothe D, Gaffney DK, Wilson BD, Lloyd S. Increased risk of death due to heart disease after radiotherapy for esophageal cancer. J Gastrointest Oncol. 2015;6(5):516–23. https://doi.org/10.3978/j.issn.2078-6891.2015.040
Gharzai L, Verma V, Denniston KA, Bhirud AR, Bennion NR, 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(7):e0158916. https://doi.org/10.1371/journal.pone.0158916
Lyon AR, López‐Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler‐Klein J, et al. 2022 ESC guidelines on cardio‐oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio‐Oncology Society (IC‐OS). Eur Heart J ‐ Cardiovasc Imaging. 2022;23(10):e333–465. https://doi.org/10.1093/ehjci/jeac106
Jia ZT, Yan YQ, Wang JX, Yang H, Zhan HH, Chen Q, et al. Development and validation of prognostic nomogram in patients with WHO grade III meningioma: a retrospective cohort study based on SEER database. Front Oncol. 2021;11:719974. https://doi.org/10.3389/fonc.2021.719974
Iasonos A, Schrag D, Raj GV, Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008;26(8):1364–70. https://doi.org/10.1200/jco.2007.12.9791
Eads JR. Cardiovascular concerns in the management of esophageal cancer patients. JACC: CardioOncol. 2021;3(5):722–4. https://doi.org/10.1016/j.jaccao.2021.11.005
Li JX, Jia YB, Cheng YF, Wang JB. Chemoradiotherapy vs radiotherapy for nonoperative early stage esophageal cancer: a seer data analysis. Cancer Med. 2020;9(14):5025–34. https://doi.org/10.1002/cam4.3132
Suzuki G, Yamazaki H, Aibe N, Masui K, Kimoto T, SHIMIZU D, et al. Definitive radiotherapy for older patients aged ≥75 years with localized esophageal cancer. In Vivo. 2019;33(3):925–32. https://doi.org/10.21873/invivo.11560
Sarkar RR, Hatamipour A, Panjwani N, Courtney PT, Cherry DR, Salans MA, et al. Impact of radiation on cardiovascular outcomes in older resectable esophageal cancer patients with Medicare. Am J Clin Oncol. 2021;44(6):275–82. https://doi.org/10.1097/coc.0000000000000815
Song EY, Venkat P, Fradley M, Frakes JM, Klocksieben F, Fontaine J, et al. Clinical factors associated with the development of postoperative atrial fibrillation in esophageal cancer patients receiving multimodality therapy before surgery. J Gastrointest Oncol. 2020;11(1):68–75. https://doi.org/10.21037/jgo.2019.12.05
Yu G, Yuexin Y, Yin L, Yiyin Z, Mei K, Liyang Z, et al. Mortality risk factors and SOX2 and mTOR expression in patients with esophageal cancer. Cell Mol Biol. 2022;67(40):346–57. https://doi.org/10.14715/cmb/2021.67.4.40
Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40. https://doi.org/10.1056/NEJMoa040694
Qiu BZ, Zhou Y, Lou M, Zhang K, Lu JW, Tong JC. The effect of the appropriate timing of radiotherapy on survival benefit in patients with metastatic esophageal cancer who have undergone resection of primary site: a SEER database analysis. J Oncol. 2022;2022:1–6. https://doi.org/10.1155/2022/6086953
Mücke T, Konen M, Wagenpfeil S, Kesting MR, Wolff KD, Hölzle F. Low‐dose preoperative chemoradiation therapy compared with surgery alone with or without postoperative radiotherapy in patients with head and neck carcinoma. Ann Surg Oncol. 2011;18(10):2739–47. https://doi.org/10.1245/s10434-011-1643-1
Garg PK, Sharma J, Jakhetiya A, Goel A, Gaur MK. Preoperative therapy in locally advanced esophageal cancer. World J Gastroenterol. 2016;22(39):8750–9. https://doi.org/10.3748/wjg.v22.i39.8750
Glimelius B, Isacsson U, Jung B, Påhlman L. Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose‐response effect favoring preoperative treatment. Int J Radiat Oncol Biol Phys. 1997;37(2):281–7. https://doi.org/10.1016/s0360-3016(96)00510-x
Zhang J, Lv Y, Chen F, Wang X, Zhang L, Zhang X. Doses of intensity‐modulated radiotherapy and its association with cardiac disease in esophageal cancer patients. Ann Transl Med. 2021;9(2):166. https://doi.org/10.21037/atm-21-184
Quintero‐Martinez JA, Cordova‐Madera SN, Villarraga HR. Radiation‐induced heart disease. J Clin Med. 2021;11(1):146. https://doi.org/10.3390/jcm11010146
Astrup Søndergaard MM, Nordsmark M, Sloth Møller D, Melgaard Nielsen K, Poulsen SH. Reduction in myocardial function and oxygen consumption after chemoradiotherapy in patients with esophageal cancer. Acta Oncol. 2022;61(5):566–74. https://doi.org/10.1080/0284186x.2022.2048068
Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, et al. 5‐fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol. 2018;10:175883591878014. https://doi.org/10.1177/1758835918780140
Albertsson M. Chemoradiotheraphy of esophageal cancer. Acta Oncol. 2002;41(2):118–23. https://doi.org/10.1080/028418602753669472
More LA, Lane S, Asnani A. 5‐FU cardiotoxicity: vasospasm, myocarditis, and sudden death. Curr Cardiol Rep. 2021;23(3):17. https://doi.org/10.1007/s11886-021-01441-2
Amin NP, Desai N, Kim SM, Agarwal M, Amin NP. Cardiac monitoring for thoracic radiation therapy: survey of practice patterns in the United States. Am J Clin Oncol. 2020;43(4):249–56. https://doi.org/10.1097/coc.0000000000000666
Agha A, Zarifa A, Kim P, Iliescu C, Gladish G, Hassan S, et al. The role of cardiovascular imaging and serum biomarkers in identifying cardiotoxicity related to cancer therapeutics. Methodist Debakey Cardiovasc J. 2019;15(4):258–66. https://doi.org/10.14797/mdcj-15-4-258
Hoeger CW, Hayek SS. Role of cardiovascular biomarkers in the risk stratification, monitoring, and management of patients with cancer. Cardiol Clin. 2019;37(4):505–23. https://doi.org/10.1016/j.ccl.2019.07.015
Manolis AA, Manolis TA, Mikhailidis DP, Manolis AS. Cardiovascular safety of oncologic agents: a double‐edged sword even in the era of targeted therapies ‐ part 2. Expert Opin Drug Saf. 2018;17(9):893–915. https://doi.org/10.1080/14740338.2018.1513489
Venneri L, Zoppellaro G, Khattar RS. Cardio‐oncology: the role of advanced echocardiography in cancer patients. Expert Rev Cardiovasc Ther. 2018;16(4):249–58. https://doi.org/10.1080/14779072.2018.1443394
Badano LP, Muraru D, Ciambellotti F, Caravita S, Guida V, Tomaselli M, et al. Assessment of left ventricular diastolic function by three‐dimensional transthoracic echocardiography. Echocardiography. 2020;37(11):1951–6. https://doi.org/10.1111/echo.14782
Morariu VI, Arnautu DA, Morariu SI, Popa AM, Parvanescu T, Andor M, et al. 2D speckle tracking: a diagnostic and prognostic tool of paramount importance. Eur Rev Med Pharmacol Sci. 2022;26(11):3903–10. https://doi.org/10.26355/eurrev_202206_28958
Wei XT, Lin L, Zhang GZ, Zhou XH. Cardiovascular magnetic resonance imaging in the early detection of cardiotoxicity induced by cancer therapies. Diagnostics. 2022;12(8):1846. https://doi.org/10.3390/diagnostics12081846
Jokar N, Amini A, Ravanbod M, Barekat M, Shooli H, Gholamrezanezhad A, et al. State‐of‐the‐art modalities in cardio‐oncology: insight from a nuclear medicine approach. Nuclear Med Rev. 2021;24(2):82–92. https://doi.org/10.5603/nmr.2021.0019
Kwan JM, Oikonomou EK, Henry ML, Sinusas AJ. Multimodality advanced cardiovascular and molecular imaging for early detection and monitoring of cancer therapy‐associated cardiotoxicity and the role of artificial intelligence and big data. Front Cardiovasc Med. 2022;9:829553. https://doi.org/10.3389/fcvm.2022.829553
Pang L, Liu ZC, Wei F, Cai CZ, Yang X. Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel exploratory tools. Arch Toxicol. 2021;95(3):791–805. https://doi.org/10.1007/s00204-020-02952-7
Bergom C, Bradley JA, Ng AK, Samson P, Robinson C, Lopez‐Mattei J, et al. Past, present, and future of radiation‐induced cardiotoxicity: refinements in targeting, surveillance, and risk stratification. JACC: CardioOncology. 2021;3(3):343–59. https://doi.org/10.1016/j.jaccao.2021.06.007
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
