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References 1. Schwartz RG, McKenzie WB, Alexander J, Sager P, D’Souza A, Manatunga A, Schwartz PE, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med. 1987; 82:1109-18. 10.1016/0002-9343(87)90212-9 2. Mason JW, Bristow MR, Billingham ME, Daniels JR. Invasive and non invasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978; 62:857-64. 3

of data from these trials, adjuvant trastuzumab has become the foundation of care for HER2- positive early breast cancer. Its use as an adjuvant treatment for a period of 1 year is currently an international standard of care in HER 2 - overexpressed localised breast cancer. It is generally well tolerated, with a low incidence of adverse effects [ 11 ] of which the most relevant is cardiotoxicity. It is typically manifested by an asymptomatic decrease in left ventricular ejection fraction (LVEF) and less often by clinical heart failure (HF) [ 12 ]. The mechanisms of

References 1. Imbach P, Kuhne T, Arceci RJ. Introduction: Incidence and management of childhood cancer. In Imbach P, Kuhne T, Arceci RJ (editors). Pediatric Oncology, a comprehensive guide. Springer-Verlag Berlin Heidelberg. 2011; XVII-IX DOI: 10.1007/978-3-642-20359-6 2. Sági JC, Egyed B, Kelemen A, Kutszegi N, Gezsi A, Herlitschke MA, et al. Possible roles of genetic variations in chemotherapy related cardiotoxicity in pediatric acute lymphoblastic leukemia and osteosarcoma. BMC Cancer. 2018; 18(1):704 DOI: 10.1186/s12885-018-4629-6 3. Spector LG, Ross JA

and heart toxicity of a concurrent association of trastuzumab and locoregional breast radiotherapy including internal mammary chain: a single-institution study. Eur J Cancer 2011; 47: 65-73. 12. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Traastuzumab after adjuvant chemotherapy in HER-2 positive breast cancer. N Engl J Med 2005; 353: 1659-72. 13. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 1973; 32: 302-14. 14. Ewer MS, Ewer SM. Cardiotoxicity of

, 3 , 4 The patients treated with adjuvant radiotherapy (RT) of the breast or chest wall receive trastuzumab concurrently with RT. Treatment with trastuzumab results in a small to modest cardiotoxicity risk. 5 , 6 , 7 RT could be cardiotoxic as well. 8 , 9 , 10 Longterm effects of concomitant treatment with trastuzumab and RT have not yet been known, the most important of which is the issue of cardiotoxicity. Reduced left ventricular ejection fraction (LVEF) and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels represent early parameters of

References 1. Harake D, Franco VI, Henkel JM, Miller TL, Lipshultz SE. Cardiotoxicity in childhood cancer survivors: strategies for prevention and management. Future Cardiol. 2012;8(4):647-70. DOI: 10.2217/fca.12.44 2. Gillespie HS, McGann CJ, Wilson BD. Noninvasive diagnosis of chemotherapy related cardiotoxicity. Curr Cardio Rev. 2011; 7: 234-44. DOI: 10.2174/157340311799960672 3. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014; 64(9): 938-45. DOI: 10.1016/j. jacc.2014.06.1167 4

References 1. Cancer Research UK, http://www.cancerresearchuk. org/health-professional/cancer-statistics, Accessed: May, 2018. 2. Ilic M, Ilic I. Cancer mortality in Serbia, 1991-2015: an age-period-cohort and joinpoint regression analysis.Cancer Commun (Lond). 2018 Apr 10;38(1):10. 3. Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102(1):14-25. 4. Vignot S, Andre T, Caux C, Bouleuc C, Evrard S, Goncalves A, Lacroix M

Summary

Previous studies have shown that palladium has toxic effects on the kidney and liver, leads to deterioration of the general condition of animals, and could cause allergy in animals and humans. Considering the limited data about the influence of palladium on the cardiovascular system, the aim of our study was to evaluate the effects of palladium on the heart from available published data, and to compare the toxicity of inorganic and organic palladium compounds. Relevant studies for our review were identified from PubMed and Scopus databases. The search terms included »palladium «, »palladium compound«, »cardiotoxicity«, »toxicity«, »heart«, »myocardium«, »oxidative stress« and »myocardial enzyme«, as well as combinations of these terms. There were only two published studies with the primary purpose to investigate the effect of palladium on the cardiovascular system, while others registered the side-effects of palladium compounds on the heart. Palladium could cause arrhythmias, a drop in blood pressure, decrease of the heart rate, as well as death of experimental animals. Based on the presented data it seems that palladium does not express significant cardiac toxicity when it is bound in an organic compound. Further investigation of the effects of palladium on the heart is necessary for a clear picture of the nature and extent of its cardiac toxicity.

-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495-502. 4. Palumbo A, Anderson K. Medical progress. Multiple myeloma. N Engl J Med 2011; 364 : 1046-60. 5. Zver S, Zadnik V, Cernelc P, Koželj M. Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation. Int J Haematology 2008; 88 : 227-36. 6. Braverman AC, Antin JH, Plappert MT. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin

(doxorubicin encapsulated in liposomes). Cancer Res. 1993; 53: 2796–802. 37. Safra T., Muggia F., Jeffers S. et a l.: Pegylated liposomal doxorubicin (Doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m 2 . Ann. Oncol. 2000; 11: 1029–1033. 38. O’Brien M.E., Wigler N., Inbar M. et al .: Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (Caelyx/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann. Oncol. 2004; 15: 440–449. 39