The cardiac toxicity of radiotherapy – a review of characteristics, mechanisms, diagnosis, and prevention

References

• Abd-ElRaouf A, Nada AS, Mohammed NEA, Amer HA, Abd-ElRahman SS, Abdelsalam RM, Salem HA. 2021. Low dose gamma irradiation attenuates cyclophosphamide-induced cardiotoxicity in rats: role of NF-kappaB signaling pathway. Int J Radiat Biol. 97(5):632–641.
   PubMed Web of Science ®Google Scholar
• Ahamed J, Laurence J. 2017. Role of platelet-derived transforming growth factor-β1 and reactive oxygen species in radiation-induced organ fibrosis. Antioxid Redox Signal. 27(13):977–988.
   PubMed Web of Science ®Google Scholar
• Alonso-Gonzalez C, Gonzalez A, Martinez-Campa C, Menendez-Menendez J, Gomez-Arozamena J, Garcia-Vidal A, Cos S. 2016. Melatonin enhancement of the radiosensitivity of human breast cancer cells is associated with the modulation of proteins involved in estrogen biosynthesis. Cancer Lett. 370(1):145–152.
   PubMed Web of Science ®Google Scholar
• Atkins KM, Chaunzwa TL, Lamba N, Bitterman DS, Rawal B, Bredfeldt J, Williams CL, Kozono DE, Baldini EH, Nohria A, et al. 2021. Association of left anterior descending coronary artery radiation dose with major adverse cardiac events and mortality in patients with non-small cell lung cancer. JAMA Oncol. 7(2):206–219.
   PubMed Web of Science ®Google Scholar
• Badakhshi H, Gruen A, Graf R, Boehmer D, Budach V. 2014. Image-guided intensity-modulated radiotherapy for patients with locally advanced gastric cancer: a clinical feasibility study. Gastric Cancer. 17(3):537–541.
   PubMed Web of Science ®Google Scholar
• Bahig H, de Guise J, Vu T, Blais D, Chartrand-Lefebvre C, Nguyen NT, Lavertu S, Guay JP, Bedwani S, Roberge D. 2018. In a heartbeat: an assessment of dynamic dose variation to cardiac structures using dual source computed tomography. Int J Radiat Oncol Biol Phys. 102(4):950–959.
   PubMed Web of Science ®Google Scholar
• Baselet B, Sonveaux P, Baatout S, Aerts A. 2019. Pathological effects of ionizing radiation: endothelial activation and dysfunction. Cell Mol Life Sci. 76(4):699–728.
   PubMed Web of Science ®Google Scholar
• Bouillon K, Haddy N, Delaloge S, Garbay JR, Garsi JP, Brindel P, Mousannif A, Le MG, Labbe M, Arriagada R, et al. 2011. Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol. 57(4):445–452.
   PubMed Web of Science ®Google Scholar
• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68(6):394–424.
   PubMed Web of Science ®Google Scholar
• Brockelmann PJ, Sasse S, Engert A. 2018. Balancing risk and benefit in early-stage classical Hodgkin lymphoma. Blood. 131(15):1666–1678.
   PubMed Web of Science ®Google Scholar
• Campbell BA, Hornby C, Cunninghame J, Burns M, MacManus M, Ryan G, Lau E, Seymour JF, Wirth A. 2012. Minimising critical organ irradiation in limited stage Hodgkin lymphoma: a dosimetric study of the benefit of involved node radiotherapy. Ann Oncol. 23(5):1259–1266.
   PubMed Web of Science ®Google Scholar
• Chang JY, Zhang W, Komaki R, Choi NC, Chan S, Gomez D, O'Reilly M, Jeter M, Gillin M, Zhu X, et al. 2017. Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer. Radiother Oncol. 122(2):274–280.
   PubMed Web of Science ®Google Scholar
• Christersdottir T, Pirault J, Gistera A, Bergman O, Gallina AL, Baumgartner R, Lundberg AM, Eriksson P, Yan ZQ, Paulsson-Berne G, et al. 2019. Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade. Eur Heart J. 40(30):2495–2503.
   PubMed Web of Science ®Google Scholar
• Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, Bogart JA, Dobelbower MC, Bosch W, Galvin JM, et al. 2017. Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. JCO. 35(1):56–62.
   PubMed Web of Science ®Google Scholar
• Chung E, Corbett JR, Moran JM, Griffith KA, Marsh RB, Feng M, Jagsi R, Kessler ML, Ficaro EC, Pierce LJ. 2013. Is there a dose-response relationship for heart disease with low-dose radiation therapy? Int J Radiat Oncol Biol Phys. 85(4):959–964.
   PubMed Web of Science ®Google Scholar
• Chung Y, Yu JI, Park W, Choi DH. 2019. Korean first prospective phase ii study, feasibility of prone position in postoperative whole breast radiotherapy: a dosimetric comparison. Cancer Res Treat. 51(4):1370–1379.
   PubMed Web of Science ®Google Scholar
• Cutter DJ, Schaapveld M, Darby SC, Hauptmann M, van Nimwegen FA, Krol AD, Janus CP, van Leeuwen FE, and Aleman BM. 2015. Risk of valvular heart disease after treatment for Hodgkin lymphoma. J Natl Cancer Inst. 107(4):djv008.
   PubMedGoogle Scholar
• Criswell T, Beman M, Araki S, Leskov K, Cataldo E, Mayo LD, Boothman DA. 2005. Delayed activation of insulin-like growth factor-1 receptor/Src/MAPK/Egr-1 signaling regulates clusterin expression, a pro-survival factor. J Biol Chem. 280(14):14212–14221.
   PubMed Web of Science ®Google Scholar
• Daniels LA, Krol AD, de Graaf MA, Scholte AJ, Van't Veer MB, Putter H, de Roos A, Schalij MJ, Creutzberg CL. 2014. Screening for coronary artery disease after mediastinal irradiation in Hodgkin lymphoma survivors: phase II study of indication and acceptance†. Ann Oncol. 25(6):1198–1203.
   PubMed Web of Science ®Google Scholar
• Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, et al. 2013. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 368(11):987–998.
   PubMed Web of Science ®Google Scholar
• 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(8):557–565.
   PubMed Web of Science ®Google Scholar
• Demissei BG, Freedman G, Feigenberg SJ, Plastaras JP, Maity A, Smith AM, McDonald C, Sheline K, Simone CB, 2nd, Lin LL, et al. 2019. Early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy for breast cancer, lung cancer, and lymphoma. Int J Radiat Oncol Biol Phys. 103(4):851–860.
   PubMed Web of Science ®Google Scholar
• Dess RT, Sun Y, Matuszak MM, Sun G, Soni PD, Bazzi L, Murthy VL, Hearn JWD, Kong FM, Kalemkerian GP, et al. 2017. Cardiac events after radiation therapy: combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer. J Clin Oncol. 35(13):1395–1402.
   PubMed Web of Science ®Google Scholar
• Dreyfuss AD, Goia D, Shoniyozov K, Shewale SV, Velalopoulou A, Mazzoni S, Avgousti H, Metzler SD, Bravo PE, Feigenberg SJ, et al. 2021. A novel mouse model of radiation-induced cardiac injury reveals biological and radiological biomarkers of cardiac dysfunction with potential clinical relevance. Clin Cancer Res. 27(8):2266–2276.
   PubMed Web of Science ®Google Scholar
• El-Mahdy MA, Alzarie YA, Hemann C, Badary OA, Nofal S, Zweier JL. 2020. The novel SOD mimetic GC4419 increases cancer cell killing with sensitization to ionizing radiation while protecting normal cells. Free Radic Biol Med. 160:630–642.
   PubMed Web of Science ®Google Scholar
• Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, et al. 2019. Genetic variants associated with cancer therapy-induced cardiomyopathy. Circulation. 140(1):31–41.
   PubMed Web of Science ®Google Scholar
• Gomez DR, Yusuf SW, Munsell MF, Welsh JW, Liao Z, Lin SH, Pan HY, Chang JY, Komaki R, Cox JD, et al. 2014. Prospective exploratory analysis of cardiac biomarkers and electrocardiogram abnormalities in patients receiving thoracic radiation therapy with high-dose heart exposure. J Thorac Oncol. 9(10):1554–1560.
   PubMed Web of Science ®Google Scholar
• Guberina M, Eberhardt W, Stuschke M, Gauler T, Heinzelmann F, Cheufou D, Kimmich M, Friedel G, Schmidberger H, Darwiche K, et al. 2017. Heart dose exposure as prognostic marker after radiotherapy for resectable stage IIIA/B non-small-cell lung cancer: secondary analysis of a randomized trial. Ann Oncol. 28(5):1084–1089.
   PubMed Web of Science ®Google Scholar
• Hooning MJ, Botma A, Aleman BM, Baaijens MH, Bartelink H, Klijn JG, Taylor CW, van Leeuwen FE. 2007. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 99(5):365–375.
   PubMedGoogle Scholar
• Hoppe BS, Flampouri S, Su Z, Morris CG, Latif N, Dang NH, Lynch J, Li Z, Mendenhall NP. 2012. Consolidative involved-node proton therapy for Stage IA-IIIB mediastinal Hodgkin lymphoma: preliminary dosimetric outcomes from a phase II study. Int J Radiat Oncol Biol Phys. 83(1):260–267.
   PubMed Web of Science ®Google Scholar
• Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, et al. 2010. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res. 87(4):656–664.
   PubMed Web of Science ®Google Scholar
• Jagsi R, Griffith KA, Moran JM, Ficaro E, Marsh R, Dess RT, Chung E, Liss AL, Hayman JA, Mayo CS, et al. 2018. A randomized comparison of radiation therapy techniques in the management of node-positive breast cancer: primary outcomes analysis. Int J Radiat Oncol Biol Phys. 101(5):1149–1158.
   PubMed Web of Science ®Google Scholar
• Jaworski C, Mariani JA, Wheeler G, Kaye DM. 2013. Cardiac complications of thoracic irradiation. J Am Coll Cardiol. 61(23):2319–2328.
   PubMed Web of Science ®Google Scholar
• Kale S, Korcum AF, Dundar E, Erin N. 2020. HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators. Naunyn Schmiedebergs Arch Pharmacol. 393(2):253–262.
   PubMed Web of Science ®Google Scholar
• Karam HM, Radwan RR. 2019. Metformin modulates cardiac endothelial dysfunction, oxidative stress and inflammation in irradiated rats: a new perspective of an antidiabetic drug. Clin Exp Pharmacol Physiol. 46(12):1124–1132.
   PubMed Web of Science ®Google Scholar
• Kenchegowda D, Legesse B, Hritzo B, Olsen C, Aghdam S, Kaur A, Culp W, Derrien-Colemyn A, Severson G, Moroni M. 2018. Selective insulin-like growth factor resistance associated with heart hemorrhages and poor prognosis in a novel preclinical model of the hematopoietic acute radiation syndrome. Radiat Res. 190(2):164–175.
   PubMed Web of Science ®Google Scholar
• Klokov D, Leskov K, Araki S, Zou Y, Goetz EM, Luo X, Willson D, Boothman DA. 2013. Low dose IR-induced IGF-1-sCLU expression: a p53-repressed expression cascade that interferes with TGFβ1 signaling to confer a pro-survival bystander effect . Oncogene. 32(4):479–490.
   PubMed Web of Science ®Google Scholar
• Kura B, Kalocayova B, LeBaron TW, Frimmel K, Buday J, Surovy J, Slezak J. 2019. Regulation of microRNAs by molecular hydrogen contributes to the prevention of radiation-induced damage in the rat myocardium. Mol Cell Biochem. 457(1-2):61–72.
   PubMed Web of Science ®Google Scholar
• Kura B, Babal P, Slezak J. 2017. Implication of microRNAs in the development and potential treatment of radiation-induced heart disease. Can J Physiol Pharmacol. 95(10):1236–1244.
   PubMed Web of Science ®Google Scholar
• Ky B, Putt M, Sawaya H, French B, Januzzi JL, Sebag IA, Plana JC, Cohen V, Banchs J, Carver JR, et al. 2014. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 63(8):809–85.
   PubMed Web of Science ®Google Scholar
• Leask A. 2010. Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ Res. 106(11):1675–1680.
   PubMed Web of Science ®Google Scholar
• Li X, Ding D, Chen W, Liu Y, Pan H, Hu J. 2021. Growth differentiation factor 11 mitigates cardiac radiotoxicity via activating AMPKalpha. Free Radic Res. 55(2):176–185.
   PubMed Web of Science ®Google Scholar
• Li X, Cui W, Hull L, Wang L, Yu T, Xiao M. 2020. IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice. Sci Rep. 10(1):18674.
   PubMed Web of Science ®Google Scholar
• Liao Z, Lee JJ, Komaki R, Gomez DR, O'Reilly MS, Fossella FV, Blumenschein GR, Jr., Heymach JV, Vaporciyan AA, Swisher SG, et al. 2018. Bayesian adaptive randomization trial of passive scattering proton therapy and intensity-modulated photon radiotherapy for locally advanced non-small-cell lung cancer. J Clin Oncol. 36(18):1813–1822.
   PubMed Web of Science ®Google Scholar
• Mapuskar KA, Flippo KH, Schoenfeld JD, Riley DP, Strack S, Hejleh TA, Furqan M, Monga V, Domann FE, Buatti JM, et al. 2017. Mitochondrial superoxide increases age-associated susceptibility of human dermal fibroblasts to radiation and chemotherapy. Cancer Res. 77(18):5054–5067.
   PubMed Web of Science ®Google Scholar
• Maraldo MV, Brodin NP, Aznar MC, Vogelius IR, Munck af Rosenschold P, Petersen PM, Specht L. 2013. Estimated risk of cardiovascular disease and secondary cancers with modern highly conformal radiotherapy for early-stage mediastinal Hodgkin lymphoma. Ann Oncol. 24(8):2113–2118.
   PubMed Web of Science ®Google Scholar
• Minasian LM, Dimond E, Davis M, Adhikari B, Fagerstrom R, Fabian C, Floyd J, Unger JM, Douglas PS, Mustian KM, et al. 2019. The evolving design of NIH-funded cardio-oncology studies to address cancer treatment-related cardiovascular toxicity. JACC Cardiooncol. 1(1):105–113.
   PubMedGoogle Scholar
• Naimi Z, Moujahed R, Neji H, Yahyaoui J, Hamdoun A, Bohli M, Kochbati L. 2021. Cardiac substructures exposure in left-sided breast cancer radiotherapy: is the mean heart dose a reliable predictor of cardiac toxicity? Cancer Radiother. 25(3):229–236
   PubMed Web of Science ®Google Scholar
• Ning MS, Tang L, Gomez DR, Xu T, Luo Y, Huo J, Mouhayar E, Liao Z. 2017. Incidence and predictors of pericardial effusion after chemoradiation therapy for locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 99(1):70–79.
   PubMed Web of Science ®Google Scholar
• Palumbo I, Palumbo B, Fravolini ML, Marcantonini M, Perrucci E, Latini ME, Falcinelli L, Sabalich I, Tranfaglia C, Schillaci G, et al. 2016. Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: a prospective study. Breast. 25:45–50
   PubMed Web of Science ®Google Scholar
• Pavo N, Raderer M, Hulsmann M, Neuhold S, Adlbrecht C, Strunk G, Goliasch G, Gisslinger H, Steger GG, Hejna M, et al. 2015. Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality. Heart. 101(23):1874–1880.
   PubMed Web of Science ®Google Scholar
• Ping Z, Peng Y, Lang H, Xinyong C, Zhiyi Z, Xiaocheng W, Hong Z, Liang S. 2020. Oxidative stress in radiation-induced cardiotoxicity. Oxid Med Cell Longev. 2020:3579143.
   PubMed Web of Science ®Google Scholar
• Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, Sugiura A, Cohen AS, Ali A, Do BT, et al. 2021. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature. 593(7858):282–288.
   PubMed Web of Science ®Google Scholar
• Roach MC, Robinson CG, DeWees TA, Ganachaud J, Przybysz D, Drzymala R, Rehman S, Kashani R, Bradley JD. 2018. Stereotactic body radiation therapy for central early-stage NSCLC: results of a prospective phase I/II trial. J Thorac Oncol. 13(11):1727–1732.
   PubMed Web of Science ®Google Scholar
• Saiki H, Petersen IA, Scott CG, Bailey KR, Dunlay SM, Finley RR, Ruddy KJ, Yan E, Redfield MM. 2017. Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancer. Circulation. 135(15):1388–1396.
   PubMed Web of Science ®Google Scholar
• Sakka M, Kunzelmann L, Metzger M, Grabenbauer GG. 2017. Cardiac dose-sparing effects of deep-inspiration breath-hold in left breast irradiation : Is IMRT more beneficial than VMAT? Strahlenther Onkol. 193(10):800–811.
   PubMed Web of Science ®Google Scholar
• Salata C, deAlmeida CE, Ferreira-Machado SC, Barroso RC, Nogueira LP, Mantuano A, Pickler A, Mota CL, Andrade CBV. 2021. Preliminary pre-clinical studies on the side effects of breast cancer treatment. Int J Radiat Biol. 97(7):877–887.
   PubMed Web of Science ®Google Scholar
• Sardar P, Kundu A, Chatterjee S, Nohria A, Nairooz R, Bangalore S, Mukherjee D, Aronow WS, Lavie CJ. 2017. Long-term cardiovascular mortality after radiotherapy for breast cancer: a systematic review and meta-analysis. Clin Cardiol. 40(2):73–81.
   PubMed Web of Science ®Google Scholar
• Schild SE, SL, Hillman AD, Tan HJ, Ross WL, McGinnis YA, Garces DL, Graham AA, Adjei JR, Jett and North Central C. Mayo Clinic, North Central Cancer Treatment Group 2017. Long-term results of a trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small cell lung cancer: NCCTG N0028 (Alliance). J Thorac Oncol. 12(4):697–703.
   PubMed Web of Science ®Google Scholar
• Simonetto C, Eidemuller M, Gaasch A, Pazos M, Schonecker S, Reitz D, Kaab S, Braun M, Harbeck N, Niyazi M, et al. 2019. Does deep inspiration breath-hold prolong life? Individual risk estimates of ischaemic heart disease after breast cancer radiotherapy. Radiother Oncol. 131:202–207.
   PubMed Web of Science ®Google Scholar
• Speirs CK, DeWees TA, Rehman S, Molotievschi A, Velez MA, Mullen D, Fergus S, Trovo M, Bradley JD, Robinson CG. 2017. Heart dose is an independent dosimetric predictor of overall survival in locally advanced non-small cell lung cancer. J Thorac Oncol. 12(2):293–301.
   PubMed Web of Science ®Google Scholar
• Sridharan V, Aykin-Burns N, Tripathi P, Krager KJ, Sharma SK, Moros EG, Corry PM, Nowak G, Hauer-Jensen M, Boerma M. 2014. Radiation-induced alterations in mitochondria of the rat heart. Radiat Res. 181(3):324–334.
   PubMed Web of Science ®Google Scholar
• Tang S, Otton J, Holloway L, Delaney GP, Liney G, George A, Jameson M, Tran D, Batumalai V, Thomas L, et al. 2019. Quantification of cardiac subvolume dosimetry using a 17 segment model of the left ventricle in breast cancer patients receiving tangential beam radiotherapy. Radiother Oncol. 132:257–265.
   PubMed Web of Science ®Google Scholar
• Thavendiranathan P, Negishi T, Cote MA, Penicka M, Massey R, Cho GY, Hristova K, Vinereanu D, Popescu BA, Izumo M, et al. And Succour Investigators. 2018. Single versus standard multiview assessment of global longitudinal strain for the diagnosis of cardiotoxicity during cancer therapy. JACC Cardiovasc Imag. 11:1109–1118.
   PubMed Web of Science ®Google Scholar
• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. 2015. Global cancer statistics, 2012. CA Cancer J Clin. 65(2):87–108.
   PubMed Web of Science ®Google Scholar
• Trivedi SJ, Tang S, Byth K, Stefani L, Lo Q, Otton J, Jameson M, Tran D, Batumalai V, Holloway L, et al. 2021. Segmental cardiac radiation dose determines magnitude of regional cardiac dysfunction. J Am Heart Assoc. 10(7):e019476.
   PubMed Web of Science ®Google Scholar
• van Boxtel W, Bulten BF, Mavinkurve-Groothuis AMC, Bellersen L, Mandigers CMPW, Joosten LAB, Kapusta L, de Geus-Oei LF, van Laarhoven HWM. 2015. New biomarkers for early detection of cardiotoxicity after treatment with docetaxel, doxorubicin and cyclophosphamide. Biomarkers. 20(2):143–148.
   PubMed Web of Science ®Google Scholar
• van den Bogaard VA, Ta BD, van der Schaaf A, Bouma AB, Middag AM, Bantema-Joppe EJ, van Dijk LV, van Dijk-Peters FB, Marteijn LA, de Bock GH, et al. 2017. 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. 35(11):1171–1178.
   PubMed Web of Science ®Google Scholar
• van Maaren MC, de Munck L, de Bock GH, Jobsen JJ, van Dalen T, Linn SC, Poortmans P, Strobbe LJA, Siesling S. 2016. 10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study. Lancet Oncol. 17(8):1158–1170.
   PubMed Web of Science ®Google Scholar
• van Nimwegen FA, Schaapveld M, Janus CP, Krol AD, Petersen EJ, Raemaekers JM, Kok WE, Aleman BM, van Leeuwen FE. 2015. Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med. 175(6):1007–1017.
   PubMed Web of Science ®Google Scholar
• Wang B, Wang H, Zhang M, Ji R, Wei J, Xin Y, Jiang X. 2020. Radiation-induced myocardial fibrosis: mechanisms underlying its pathogenesis and therapeutic strategies. J Cell Mol Med. 24(14):7717–7729.
   PubMed Web of Science ®Google Scholar
• Wang H, Wei J, Zheng Q, Meng L, Xin Y, Yin X, Jiang X. 2019. Radiation-induced heart disease: a review of classification, mechanism and prevention. Int J Biol Sci. 15(10):2128–2138.
   PubMed Web of Science ®Google Scholar
• Wang K, Eblan MJ, Deal AM, Lipner M, Zagar TM, Wang Y, Mavroidis P, Lee CB, Jensen BC, Rosenman JG, et al. 2017. Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. JCO. 35(13):1387–1394.
   PubMed Web of Science ®Google Scholar
• Weberpals J, Jansen L, Muller OJ, Brenner H. 2018. Long-term heart-specific mortality among 347 476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort study . Eur Heart J. 39(43):3896–3903.
   PubMed Web of Science ®Google Scholar
• Wockel A, Wolters R, Wiegel T, Novopashenny I, Janni W, Kreienberg R, Wischnewsky M, Schwentner L, Study Group B. 2014. The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects. Ann Oncol. 25(3):628–632.
   PubMed Web of Science ®Google Scholar
• Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. 2012. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma-a report from the Children's Oncology Group. J Clin Oncol. 30(26):3174–3180.
   PubMed Web of Science ®Google Scholar
• Yahyapour R, Motevaseli E, Rezaeyan A, Abdollahi H, Farhood B, Cheki M, Rezapoor S, Shabeeb D, Musa AE, Najafi M, et al. 2018. Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clin Transl Oncol. 20(8):975–988.
   PubMed Web of Science ®Google Scholar
• Yakovlev VA. 2013. Nitric oxide-dependent downregulation of BRCA1 expression promotes genetic instability. Cancer Res. 73(2):706–715.
   PubMed Web of Science ®Google Scholar
• Zamorano JL, Lancellotti P, Rodriguez Munoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, 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. 37(36):2768–2801.
   PubMed Web of Science ®Google Scholar
• Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, et al. 2007. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 13(8):952–961.
   PubMed Web of Science ®Google Scholar