High risk of cardiovascular side effects after treatment of Hodgkin’s lymphoma – is there a need for intervention in long-term survivors?

  • Anne Andersson Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden https://orcid.org/0000-0002-9597-6465
  • Beatrice Melin Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden https://orcid.org/0000-0002-9982-3757
  • Gunilla Enblad Department of Immunology, Genetics and Pathology, Section Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0002-0594-724X
  • Martin Erlanson Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
  • Ann-Sofie Johansson Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden https://orcid.org/0000-0001-5783-9489
  • Daniel Molin Department of Immunology, Genetics and Pathology, Section Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden
  • Björn Tavelin Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
  • Ulf Näslund Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden https://orcid.org/0000-0003-4100-8298
Keywords: Hodgkin lymphoma, survivorship, cardiovascular side effects, intervention

Abstract

Background: Hodgkin lymphoma (HL) patients have a good prognosis after adequate treatment. Previous treatment with mantle field irradiation has been accompanied by an increased long-term risk of cardiovascular disease (CVD). This study identified co-morbidity factors for the development of cardiovascular side effects and initiated an intervention study aimed to decrease morbidity and mortality of CVD in HL survivors.

Design: Hodgkin lymphoma patients aged ≤45 years diagnosed between 1965 and 1995 were invited to participate. In total, 453 patients completed a questionnaire that addressed co-morbidity factors and clinical symptoms. Of these, 319 accepted to participate in a structured clinical visit. The statistical analyses compared individuals with CVD with those with no CVD.

Results: Cardiovascular disease was reported by 27.9%. Radiotherapy (odds ratio [OR]: 3.27), hypertension and hypercholesterolemia were shown to be independent risk factors for the development of CVD. The OR for CVD and valve disease in patients who received radiotherapy towards mediastinum was 4.48 and 6.07, respectively. At clinical visits, 42% of the patients were referred for further investigation and 24% of these had a cardiac ultrasound performed due to previously unknown heart murmurs.

Conclusion: Radiotherapy towards mediastinum was an independent risk factor for CVD as well as hypercholesterolemia and hypertension. A reasonable approach as intervention for this cohort of patients is regular monitoring of hypertension and hypercholesterolemia and referral to adequate investigation when cardiac symptoms appear. Broad knowledge about the side effects from radiotherapy in the medical community and well-structured information regarding late side effects to the patients are all reasonable approaches as late effects can occur even 40 years after cancer treatment.

Downloads

Download data is not yet available.

References


  1. Socialstyrelsen. Cancer i siffror. National board of health and wellfare. 2018:66. Available from www.socialstyrelsen.se/globalassets/sharepoint-dokument/artikelkatalog/statistik/2018-6-10.pdf

  2. De Vita Jr. VT, Hubbard SM, Longo DL. Treatment of Hodgkin’s disease. J Natl Cancer Inst Monogr. 1990(10):19–28.

  3. Aleman BM, van den Belt-Dusebout AW, De Bruin ML, van ‘t Veer MB, Baaijens MH, de Boer JP, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007;109:1878–86. doi: 10.1182/blood-2006-07-034405

  4. Foss Abrahamsen A, Andersen A, Nome O, Jacobsen AB, Holte H, Foss Abrahamsen J, et al. Long-term risk of second malignancy after treatment of Hodgkin’s disease: the influence of treatment, age and follow-up time. Ann Oncol. 2002;13:1786–91. doi: 10.1093/annonc/mdf289

  5. Metayer C, Lynch CF, Clarke EA, Glimelius B, Storm H, Pukkala E, et al. Second cancers among long-term survivors of Hodgkin’s disease diagnosed in childhood and adolescence. J Clin Oncol. 2000;18:2435–43. doi: 10.1200/JCO.2000.18.12.2435

  6. Swerdlow AJ, Barber JA, Hudson GV, Cunningham D, Gupta RK, Hancock BW, et al. Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol. 2000;18:498–509. doi: 10.1200/jco.2000.18.3.498

  7. Swerdlow AJ, Higgins CD, Smith P, Cunningham D, Hancock BW, Horwich A, et al. Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J Natl Cancer Inst. 2007;99:206–14. doi: 10.1093/jnci/djk029

  8. Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B, et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin’s disease. J Natl Cancer Inst. 2002;94:182–92. doi: 10.1093/jnci/94.3.182

  9. Glanzmann C, Kaufmann P, Jenni R, Hess OM, Huguenin P. Cardiac risk after mediastinal irradiation for Hodgkin’s disease. Radiother Oncol;1998;46:51–62. doi: 10.1016/S0167-8140(97)00125-4

  10. Dores GM, Metayer C, Curtis RE, Lynch CF, Clarke EA, Glimelius B, et al. Second malignant neoplasms among long-term survivors of Hodgkin’s disease: a population-based evaluation over 25 years. J Clin Oncol. 2002;20:3484–94. doi: 10.1200/jco.2002.09.038

  11. van Nimwegen FA, Schaapveld M, Janus CP, Krol AD, Petersen EJ, Raemaekers JM, et al. Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med. 2015;175:1007–17. doi: 10.1001/jamainternmed.2015.1180

  12. van Leeuwen FE, Ng AK. Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment. Hematology. 2016;1:323–30. doi: 10.1182/asheducation-2016.1.323

  13. Aleman BM, van den Belt-Dusebout AW, Klokman WJ, Van’t Veer MB, Bartelink H, van Leeuwen FE. Long-term cause-specific mortality of patients treated for Hodgkin’s disease. J Clin Oncol. 2003;21:3431–9. doi: 10.1200/jco.2003.07.131

  14. Engert A, Plutschow A, Eich HT, Lohri A, Dorken B, Borchmann P, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med. 2010;363:640–52. doi: 10.1056/nejmoa1000067

  15. Ng AK, Bernardo MP, Weller E, Backstrand KH, Silver B, Marcus KC, et al. Long-term survival and competing causes of death in patients with early-stage Hodgkin’s disease treated at age 50 or younger. J Clin Oncol. 2002;20:2101–8. doi: 10.1200/jco.2002.08.021

  16. Ng AK. Current survivorship recommendations for patients with Hodgkin lymphoma: focus on late effects. Hematology. 2014;1:488–94. doi: 10.1182/asheducation-2014.1.488

  17. van Nimwegen FA, Ntentas G, Darby SC, Schaapveld M, Hauptmann M, Lugtenburg PJ, et al. Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines. Blood. 2017;129:2257–65. doi: 10.1182/blood-2016-09-740332

  18. Dahlof B. Cardiovascular disease risk factors: epidemiology and risk assessment. Am J Cardiol. 2010;105:3A–9A. doi: 10.1016/j.amjcard.2009.10.007

  19. Bijl JM, Roos MM, van Leeuwen-Segarceanu EM, Vos JM, Bos WW, Biesma DH, et al. Assessment of valvular disorders in survivors of Hodgkin’s lymphoma treated by mediastinal radiotherapy +/- chemotherapy. Am J Cardiol. 2016;117:691–6. doi: 10.1016/j.amjcard.2015.11.027

  20. Galper SL, Yu JB, Mauch PM, Strasser JF, Silver B, Lacasce A, et al. Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation. Blood. 2011;117:412–8. doi: 10.1182/blood-2010-06-291328

  21. Andersson A, Naslund U, Tavelin B, Enblad G, Gustavsson A, Malmer B. Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors – retrospective cohort analyses and a concept for prospective intervention. Int J Cancer. 2009;124:1914–7. doi: 10.1002/ijc.24147

  22. Chen AB, Punglia RS, Kuntz KM, Mauch PM, Ng AK. Cost effectiveness and screening interval of lipid screening in Hodgkin’s lymphoma survivors. J Clin Oncol. 2009;27:5383–9. doi: 10.1200/jco.2009.22.8460

  23. Blomstedt Y, Norberg M, Stenlund H, Nystrom L, Lonnberg G, Boman K, et al. Impact of a combined community and primary care prevention strategy on all-cause and cardiovascular mortality: a cohort analysis based on 1 million person-years of follow-up in Vasterbotten County, Sweden, during 1990–2006. BMJ Open. 2015;5:e009651. doi: 10.1136/bmjopen-2015-009651

  24. Lindholm L, Stenling A, Norberg M, Stenlund H, Weinehall L. A cost-effectiveness analysis of a community based CVD program in Sweden based on a retrospective register cohort. BMC Public Health. 2018;18:452. doi: 10.1186/s12889-018-5339-3

  25. van Leeuwen-Segarceanu EM, Bos WJ, Dorresteijn LD, Rensing BJ, der Heyden JA, Vogels OJ, et al. Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. Cancer Treat Rev. 2011;37:391–403. doi: 10.1016/j.ctrv.2010.12.004

Published
2021-03-15
How to Cite
Andersson, A., Melin, B., Enblad, G., Erlanson, M., Johansson, A.-S., Molin, D., Tavelin, B., & Näslund, U. (2021). High risk of cardiovascular side effects after treatment of Hodgkin’s lymphoma – is there a need for intervention in long-term survivors?. Upsala Journal of Medical Sciences, 126(1). https://doi.org/10.48101/ujms.v126.6117
Section
Original Articles