1932

Abstract

Treatment advances have increased survival in children with cancer, but subclinical, progressive, irreversible, and sometimes fatal treatment-related cardiovascular effects may appear years later. Cardio-oncologists have identified promising preventive and treatment strategies. Dexrazoxane provides long-term cardioprotection from doxorubicin-associated cardiotoxicity without compromising the efficacy of anticancer treatment. Continuous infusion of doxorubicin is as effective as bolus administration in leukemia treatment, but no evidence has indicated that it provides long-term cardioprotection; continuous infusions should be eliminated from pediatric cancer treatment. Angiotensin-converting enzyme inhibitors can delay the progression of subclinical and clinical cardiotoxicity. All survivors, regardless of whether they were treated with anthracyclines or radiation, should be monitored for systemic inflammation and the risk of premature cardiovascular disease. Echocardiographic screening must be supplemented with screening for biomarkers of cardiotoxicity and perhaps by identification of genetic susceptibilities to cardiovascular diseases; optimal strategies need to be identified. The health burden related to cancer treatment will increase as this population expands and ages.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-070213-054849
2015-01-14
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/med/66/1/annurev-med-070213-054849.html?itemId=/content/journals/10.1146/annurev-med-070213-054849&mimeType=html&fmt=ahah

Literature Cited

  1. 1. American Cancer Society 2013. Cancer Facts & Figures 2013 Atlanta: Am. Cancer Soc.
  2. Lipshultz SE, Cochran TR, Franco VI, Miller TL. 2.  2013. Treatment-related cardiotoxicity in survivors of childhood cancer. Nat. Rev. Clin. Oncol. 10:697–710 [Google Scholar]
  3. Lipshultz SE, Colan SD, Gelber RD. 3.  et al. 1991. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N. Engl. J. Med. 324:808–15 [Google Scholar]
  4. Mulrooney DA, Yeazel MW, Kawashima T. 4.  et al. 2009. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339:b4606 [Google Scholar]
  5. Oeffinger KC, Mertens AC, Sklar CA. 5.  et al. 2006. Chronic health conditions in adult survivors of childhood cancer. N. Engl. J. Med. 355:1572–82 [Google Scholar]
  6. Mertens AC, Liu Q, Neglia JP. 6.  et al. 2008. Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J. Natl. Cancer Inst. 100:1368–79 [Google Scholar]
  7. Lipshultz SE, Adams MJ. 7.  2010. Cardiotoxicity after childhood cancer: beginning with the end in mind. J. Clin. Oncol. 28:1276–81 [Google Scholar]
  8. Tukenova M, Guibout C, Oberlin O. 8.  et al. 2010. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J. Clin. Oncol. 28:1308–15 [Google Scholar]
  9. Mertens AC, Yasui Y, Neglia JP. 9.  et al. 2001. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J. Clin. Oncol. 19:3163–72 [Google Scholar]
  10. Reulen RC, Winter DL, Frobisher C. 10.  et al. 2010. Long-term cause-specific mortality among survivors of childhood cancer. JAMA 304:172–79 [Google Scholar]
  11. Nysom K, Holm K, Lipsitz SR. 11.  et al. 1998. Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. J. Clin. Oncol. 16:545–50 [Google Scholar]
  12. Lipshultz SE, Lipsitz SR, Sallan SE. 12.  et al. 2005. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J. Clin. Oncol. 23:2629–36 [Google Scholar]
  13. Kremer LC, van der Pal HJ, Offringa M. 13.  et al. 2002. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann. Oncol. 13:819–29 [Google Scholar]
  14. Adams MJ, Lipshultz SE. 14.  2005. Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention. Pediatr. Blood Cancer 44:600–6 [Google Scholar]
  15. Lipshultz SE, Miller TL, Gerschenson M. 15.  et al. 2012. Effect of dexrazoxane on impaired mitochondrial structure and function in doxorubicin-treated childhood ALL survivors. J. Clin. Oncol. 30:Suppl.9530 (Abstr.) [Google Scholar]
  16. Taniguchi I.16.  2005. Clinical significance of cyclophosphamide-induced cardiotoxicity. Intern. Med. 44:89–90 [Google Scholar]
  17. Hudis CA.17.  2007. Trastuzumab—mechanism of action and use in clinical practice. N. Engl. J. Med. 357:39–51 [Google Scholar]
  18. Albanell J, Montagut C, Jones ET. 18.  et al. 2008. A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors. Clin. Cancer Res. 14:2726–31 [Google Scholar]
  19. De Keulenaer GW, Doggen K, Lemmens K. 19.  2010. The vulnerability of the heart as a pluricellular paracrine organ: lessons from unexpected triggers of heart failure in targeted ErbB2 anticancer therapy. Circ. Res. 106:35–46 [Google Scholar]
  20. Bowles EJ, Wellman R, Feigelson HS. 20.  et al. 2012. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J. Natl. Cancer Inst. 104:1293–305 [Google Scholar]
  21. Ewer MS, Vooletich MT, Durand JB. 21.  et al. 2005. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J. Clin. Oncol. 23:7820–26 [Google Scholar]
  22. Ebb D, Meyers P, Grier H. 22.  et al. 2012. Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression: a report from the Children's Oncology Group. J. Clin. Oncol. 30:2545–51 [Google Scholar]
  23. Perez EA, Koehler M, Byrne J. 23.  et al. 2008. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin. Proc. 83:679–86 [Google Scholar]
  24. Fouladi M, Stewart CF, Blaney SM. 24.  et al. 2010. Phase I trial of lapatinib in children with refractory CNS malignancies: a Pediatric Brain Tumor Consortium study. J. Clin. Oncol. 28:4221–27 [Google Scholar]
  25. Suttorp M, Millot F. 25.  2010. Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematol. Am. Soc. Hematol. Educ. Program 2010:368–76 [Google Scholar]
  26. Kerkela R, Grazette L, Yacobi R. 26.  et al. 2006. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med. 12:908–16 [Google Scholar]
  27. Atallah E, Durand JB, Kantarjian H, Cortes J. 27.  2007. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 110:1233–37 [Google Scholar]
  28. Bond M, Bernstein ML, Pappo A. 28.  et al. 2008. A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children's Oncology Group study. Pediatr. Blood Cancer 50:254–58 [Google Scholar]
  29. Schultz KR, Bowman WP, Aledo A. 29.  et al. 2009. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a Children's Oncology Group study. J. Clin. Oncol. 27:5175–81 [Google Scholar]
  30. Herman EH, Knapton A, Rosen E. 30.  et al. 2011. A multifaceted evaluation of imatinib-induced cardiotoxicity in the rat. Toxicol. Pathol. 39:1091–106 [Google Scholar]
  31. Pavey T, Hoyle M, Ciani O. 31.  et al. 2012. Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses. Health Technol. Assess. 16:421–277 [Google Scholar]
  32. 32. US Food Drug Admin 2013. FDA Drug Safety Communication: FDA asks manufacturer of the leukemia drug Iclusig (ponatinib) to suspend marketing and sales US Food Drug Admin., Washington, DC. http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm [Google Scholar]
  33. Tefferi A.33.  2013. Nilotinib treatment-associated accelerated atherosclerosis: When is the risk justified?. Leukemia 27:1939–40 [Google Scholar]
  34. Groarke JD, Cheng S, Moslehi J. 34.  2013. Cancer-drug discovery and cardiovascular surveillance. N. Engl. J. Med. 369:1779–81 [Google Scholar]
  35. Bair SM, Choueiri TK, Moslehi J. 35.  2013. Cardiovascular complications associated with novel angiogenesis inhibitors: emerging evidence and evolving perspectives. Trends Cardiovasc. Med. 23:104–13 [Google Scholar]
  36. Rini BI, Cohen DP, Lu DR. 36.  et al. 2011. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J. Natl. Cancer Inst. 103:763–73 [Google Scholar]
  37. Chu TF, Rupnick MA, Kerkela R. 37.  et al. 2007. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370:2011–19 [Google Scholar]
  38. Telli ML, Witteles RM, Fisher GA, Srinivas S. 38.  2008. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann. Oncol. 19:1613–18 [Google Scholar]
  39. Schmidinger M, Zielinski CC, Vogl UM. 39.  et al. 2008. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 26:5204–12 [Google Scholar]
  40. Dubois SG, Shusterman S, Ingle AM. 40.  et al. 2011. Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a Children's Oncology Group study. Clin. Cancer Res. 17:5113–22 [Google Scholar]
  41. Inaba H, Rubnitz JE, Coustan-Smith E. 41.  et al. 2011. Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia. J. Clin. Oncol. 29:3293–300 [Google Scholar]
  42. Widemann BC, Kim A, Fox E. 42.  et al. 2012. A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a Children's Oncology Group Phase I Consortium report. Clin. Cancer Res. 18:6011–22 [Google Scholar]
  43. Boivin JF, Hutchison GB, Lubin JH, Mauch P. 43.  1992. Coronary artery disease mortality in patients treated for Hodgkin's disease. Cancer 69:1241–47 [Google Scholar]
  44. Adams MJ, Lipsitz SR, Colan SD. 44.  et al. 2004. Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy. J. Clin. Oncol. 22:3139–48 [Google Scholar]
  45. Landy DC, Miller TL, Lipsitz SR. 45.  et al. 2013. Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. Pediatr. Cardiol. 34:826–34 [Google Scholar]
  46. Lipshultz SE, Landy DC, Lopez-Mitnik G. 46.  et al. 2012. Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. J. Clin. Oncol. 30:1050–57 [Google Scholar]
  47. Lipshultz SE, Alvarez JA, Scully RE. 47.  2008. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart 94:525–33 [Google Scholar]
  48. Kremer LC, van Dalen EC, Offringa M. 48.  et al. 2001. Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J. Clin. Oncol. 19:191–96 [Google Scholar]
  49. Trachtenberg BH, Landy DC, Franco VI. 49.  et al. 2011. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr. Cardiol. 32:342–53 [Google Scholar]
  50. Messiah SE, Arheart KL, Lopez-Mitnik G. 50.  et al. 2013. Ethnic group differences in cardiometabolic disease risk factors independent of body mass index among American youth. Obesity 21:424–28 [Google Scholar]
  51. Landy DC, Miller TL, Lopez-Mitnik G. 51.  et al. 2012. Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. Am. Heart J. 163:295–301.e2 [Google Scholar]
  52. Ness KK, Leisenring WM, Huang S. 52.  et al. 2009. Predictors of inactive lifestyle among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 115:1984–94 [Google Scholar]
  53. Miller AM, Lopez-Mitnik G, Somarriba G. 53.  et al. 2013. Exercise capacity in long-term survivors of pediatric cancer: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. Pediatr. Blood Cancer 60:663–68 [Google Scholar]
  54. Lipshultz SE, Lipsitz SR, Kutok JL. 54.  et al. 2013. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer 119:3555–62 [Google Scholar]
  55. Blanco JG, Leisenring WM, Gonzalez-Covarrubias VM. 55.  et al. 2008. Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer. Cancer 112:2789–95 [Google Scholar]
  56. Blanco JG, Sun CL, Landier W. 56.  et al. 2012. Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes—a report from the Children's Oncology Group. J. Clin. Oncol. 30:1415–21 [Google Scholar]
  57. Visscher H, Ross CJ, Rassekh SR. 57.  et al. 2012. Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J. Clin. Oncol. 30:1422–28 [Google Scholar]
  58. Visscher H, Ross CJ, Rassekh SR. 58.  et al. 2013. Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr. Blood Cancer 60:1375–81 [Google Scholar]
  59. Miranda CJ, Makui H, Soares RJ. 59.  et al. 2003. Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin. Blood 102:2574–80 [Google Scholar]
  60. Lipshultz SE.60.  1996. Dexrazoxane for protection against cardiotoxic effects of anthracyclines in children. J. Clin. Oncol. 14:328–31 [Google Scholar]
  61. Lipshultz SE, Scully RE, Lipsitz SR. 61.  et al. 2010. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomized, multicentre trial. Lancet Oncol. 11:950–61 [Google Scholar]
  62. Wexler LH, Andrich MP, Venzon D. 62.  et al. 1996. Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J. Clin. Oncol. 14:362–72 [Google Scholar]
  63. 62a.  US Food and Drug Administration Orphan drug designations and approvals. http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?_Index_Number=441314. Accessed Sep. 2014
  64. Lipshultz SE, Rifai N, Dalton VM. 63.  et al. 2004. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N. Engl. J. Med. 351:145–53 [Google Scholar]
  65. Asselin B, Devidas M, Zhou T. 64.  et al. 2012. Cardioprotection and safety of dexrazoxane (DRZ) in children treated for newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or advanced stage lymphoblastic leukemia (T-LL). J. Clin. Oncol. 30:Suppl.9504 (Abstr.) [Google Scholar]
  66. Kopp LM, Bernstein ML, Schwartz CL. 65.  et al. 2012. The effects of dexrazoxane on cardiac status and second malignant neoplasms (SMN) in doxorubicin-treated patients with osteosarcoma (OS). J. Clin. Oncol. 30:Suppl.9503 (Abstr.) [Google Scholar]
  67. Walker DM, Fisher BT, Seif AE. 66.  et al. 2013. Dexrazoxane use in pediatric patients with acute lymphoblastic or myeloid leukemia from 1999 and 2009: analysis of a national cohort of patients in the Pediatric Health Information Systems database. Pediatr. Blood Cancer 60:616–20 [Google Scholar]
  68. Lipshultz SE, Lipsitz SR, Orav EJ. 67.  2007. Dexrazoxane-associated risk for secondary malignancies in pediatric Hodgkin's disease: a claim without compelling evidence. J. Clin. Oncol. 25:3179; author reply 3180 [Google Scholar]
  69. Hellmann K.68.  2007. Dexrazoxane-associated risk for secondary malignancies in pediatric Hodgkin's disease: a claim without evidence. J. Clin. Oncol. 25:4689–90; author reply 90–91 [Google Scholar]
  70. Cardinale D, Colombo A, Sandri MT. 69.  et al. 2006. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114:2474–81 [Google Scholar]
  71. Barry EV, Vrooman LM, Dahlberg SE. 70.  et al. 2008. Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J. Clin. Oncol. 26:1106–11 [Google Scholar]
  72. Lipshultz SE, Franco VI, Sallan SE. 70a.  et al. 2014. Dexrazoxane for reducing anthracycline-related cardiotoxicity in children with cancer: an update of the evidence. Prog. Pediatr. Cardiol In press. doi: 101016/j.ppedcard.2014.09.007
  73. Vrooman LM, Neuberg DS, Stevenson KE. 71.  et al. 2011. The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium. Eur. J. Cancer 47:1373–79 [Google Scholar]
  74. Salzer WL, Devidas M, Carroll WL. 72.  et al. 2010. Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984–2001: a report from the Children's Oncology Group. Leukemia 24:355–70 [Google Scholar]
  75. Lipshultz SE, Franco VI, Sallan SE. 73.  et al. 2014. Dexrazoxane for reducing anthracycline-related cardiotoxicity in children with cancer: an update of the evidence. Prog. Pediatr. Cardiol. 3639–49
  76. Tebbi CK, London WB, Friedman D. 74.  et al. 2007. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J. Clin. Oncol. 25:493–500 [Google Scholar]
  77. Tebbi CK, Mendenhall NP, London WB. 75.  et al. 2012. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group. Pediatr. Blood Cancer 59:1259–65 [Google Scholar]
  78. Schwartz CL, Constine LS, Villaluna D. 76.  et al. 2009. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood 114:2051–59 [Google Scholar]
  79. Chow EJ, Asselin B, Schwartz CL. 77.  et al. 2014. Late mortality and relapse after dexrazoxane (DRZ) treatment: an update from the Children's Oncology Group (COG). J. Clin. Oncol. 32:Suppl.10024 (Abstr.) [Google Scholar]
  80. Lipshultz SE, Miller TL, Lipsitz SR. 78.  et al. 2012. Continuous versus bolus infusion of doxorubicin in children with ALL: long-term cardiac outcomes. Pediatrics 130:1003–11 [Google Scholar]
  81. Levitt GA, Dorup I, Sorensen K, Sullivan I. 79.  2004. Does anthracycline administration by infusion in children affect late cardiotoxicity?. Br. J. Haematol. 124:463–68 [Google Scholar]
  82. Gupta M, Steinherz PG, Cheung NK, Steinherz L. 80.  2003. Late cardiotoxicity after bolus versus infusion anthracycline therapy for childhood cancers. Med. Pediatr. Oncol. 40:343–47 [Google Scholar]
  83. Lipshultz SE, Giantris AL, Lipsitz SR. 81.  et al. 2002. Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J. Clin. Oncol. 20:1677–82 [Google Scholar]
  84. 82. SOLVD Investig 1991. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N. Engl. J. Med. 325:293–302 [Google Scholar]
  85. Lipshultz SE, Lipsitz SR, Sallan SE. 83.  et al. 2002. Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. J. Clin. Oncol. 20:4517–22 [Google Scholar]
  86. Silber JH, Cnaan A, Clark BJ. 84.  et al. 2004. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J. Clin. Oncol. 22:820–28 [Google Scholar]
  87. Wouters KA, Kremer LC, Miller TL. 85.  et al. 2005. Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies. Br. J. Haematol. 131:561–78 [Google Scholar]
  88. van Dalen EC, Caron HN, Dickinson HO, Kremer LC. 86.  2011. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst. Rev. 2005:1CD003917 [Google Scholar]
  89. Lipshultz SE, Miller TL, Scully RE. 87.  et al. 2012. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J. Clin. Oncol. 30:1042–49 [Google Scholar]
  90. Bosch X, Rovira M, Sitges M. 88.  et al. 2013. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (prevention of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J. Am. Coll. Cardiol. 61:232355–62 [Google Scholar]
  91. Sliwa K, Norton GR, Kone N. 89.  et al. 2004. Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure. J. Am. Coll. Cardiol. 44:1825–30 [Google Scholar]
  92. Ewer MS, Yeh ET. 90.  2006. Cancer and the Heart New York: BC Decker Inc.
  93. Ward KM, Binns H, Chin C. 91.  et al. 2004. Pediatric heart transplantation for anthracycline cardiomyopathy: cancer recurrence is rare. J. Heart Lung Transplant. 23:1040–45 [Google Scholar]
  94. Lipshultz SE, Vlach SA, Lipsitz SR. 92.  et al. 2005. Cardiac changes associated with growth hormone therapy among children treated with anthracyclines. Pediatrics 115:1613–22 [Google Scholar]
  95. Lipshultz SE, Franco VI, Cochran TR. 93.  2013. Cardiotoxicity in childhood cancer survivors: a problem with long-term consequences in need of early detection and prevention. Pediatr. Blood Cancer 60:1395–96 [Google Scholar]
  96. Steiner R.94.  2013. Increasing exercise in long-term survivors of pediatric cancer and their siblings: should treatment be a family affair?. Pediatr. Blood Cancer 60:529–30 [Google Scholar]
  97. Miller TL, Lipsitz SR, Lopez-Mitnik G. 95.  et al. 2010. Characteristics and determinants of adiposity in pediatric cancer survivors. Cancer Epidemiol. Biomark. Prev. 19:2013–22 [Google Scholar]
  98. Krischer JP, Epstein S, Cuthbertson DD. 96.  et al. 1997. Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience. J. Clin. Oncol. 15:1544–52 [Google Scholar]
  99. Lipshultz SE, Lipsitz SR, Mone SM. 97.  et al. 1995. Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N. Engl. J. Med. 332:1738–43 [Google Scholar]
  100. van der Pal HJ, van Dalen EC, Hauptmann M. 98.  et al. 2010. Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study. Arch. Intern. Med. 170:1247–55 [Google Scholar]
  101. Barry E, Alvarez JA, Scully RE. 99.  et al. 2007. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin. Pharmacother. 8:1039–58 [Google Scholar]
  102. Giantris A, Abdurrahman L, Hinkle A. 100.  et al. 1998. Anthracycline-induced cardiotoxicity in children and young adults. Crit. Rev. Oncol. Hematol. 27:53–68 [Google Scholar]
  103. Lipshultz SE, Wilkinson JD. 101.  2014. Beta-adrenergic adaptation in idiopathic dilated cardiomyopathy: differences between children and adults. Eur. Heart J. 35:10–12 [Google Scholar]
/content/journals/10.1146/annurev-med-070213-054849
Loading
/content/journals/10.1146/annurev-med-070213-054849
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error