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Original research
Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study
  1. Elizabeth Arnoldina Maria Feijen1,
  2. Elvira C van Dalen1,
  3. Heleen J H van der Pal1,
  4. Raoul C Reulen2,
  5. David L Winter2,
  6. Claudia E Kuehni3,4,
  7. Vera Morsellino5,
  8. Daniela Alessi6,
  9. Rodrigue S Allodji7,
  10. Julliana Byrne8,
  11. Edit Bardi9,
  12. Zsuzsanna Jakab10,
  13. Desiree Grabow11,
  14. Stanislaw Garwicz12,
  15. Nadia Haddy13,
  16. Momcilo Jankovic14,
  17. Peter Kaatsch11,
  18. Gill A Levitt15,
  19. Cecile M Ronckers1,
  20. Christina Schindera3,
  21. Roderick Skinner16,
  22. Lorna Zalatel17,
  23. Lars Hjorth12,
  24. Wim J E Tissing1,18,
  25. Florent De Vathaire7,
  26. Mike M Hawkins2,
  27. Leontien C M Kremer1
  28. on behalf of the PanCareSurFup consortium
  1. 1Pediatric Oncology, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
  2. 2University of Birmingham, Birmingham, UK
  3. 3Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
  4. 4Pediatric Hematology and Oncology, University Children's Hospital Bern, University of Bern, Bern, Switzerland
  5. 5Giannina Gaslini Children's Hospital, Genova, Italy
  6. 6Childhood Cancer Registry of Piedmont, Torino, Italy
  7. 7Gustave Roussy, Villejuif, Île-de-France, France
  8. 8Boyne Institute, Drogheda, Ireland
  9. 9Kepler University Clinic, Linz, Austria
  10. 10Markusovszky University Teaching Hospital, Szombathely, Vas, Hungary
  11. 11University Medical Center Mainz, Mainz, Germany
  12. 12Skåne University Hospital Lund, Lund, Sweden
  13. 13INSERM, Paris, France
  14. 14Hospital San Gerardo, Monza, Italy
  15. 15Great Ormond Street Hospital for Children, London, UK
  16. 16Newcastle University, Newcastle upon Tyne, UK
  17. 17Institute of Oncology Ljubljana, Ljubljana, Slovenia
  18. 18Pediatric Oncology, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Elizabeth Arnoldina Maria Feijen, Princess Maxima Center for Pediatric Oncology, Utrecht 3720 AC, The Netherlands; e.a.m.feijen{at}prinsesmaximacentrum.nl

Abstract

Objective In this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.

Methods Eight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3–5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.

Results Overall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14–30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).

Conclusions In this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

  • myocardial disease

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Footnotes

  • Deceased SG died on the 27 Nov 2018.

  • Correction notice This article has been corrected since it was first published. The author Claudia E Keuhni should have been listed as Claudia E Kuehni, and the corresponding affiliations have been updated to include the specific departments: ‘Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland’ and ‘Pediatric Hematology and Oncology, University Children's Hospital Bern, University of Bern, Bern, Switzerland’.

  • Contributors Planning: EAMF, HJHvdP, RCR, CEK, RSA, EB, ZJ, SG, NH, PK, GAL, RS, LZ, LH, FDV, MHH, LCMK. Conduct: EAMF, ECVD, HJHvdP, RCR, DLW, CEK, VM, DA, RSA, JB, EB, ZJ, DG, SG, NH, MJ, PK, GAL, CMR, CS, RS, LZ, LH, WJET, FDV, MHH, LCMK. Reporting: EAMF, ECVD, HJHvdP, RCR, CEK, VM, DA, RSA, JB, EB, ZJ, DG, SG, NH, MJ, PK, GAL, CMR, CS, RS, LZ, LH, WJET, FDV, MHH, LCMK.

  • Funding Supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration (Grant Agreement No. 257505; PanCareSurFup). CMR was supported by grant funding from the Dutch Cancer Society. The Swiss Childhood Cancer Registry and the Swiss Childhood Cancer Survivor Study are supported by the Swiss Paediatric Oncology Group, the Swiss Cancer League (KLS-3412-02-2014, KLS-3886-02-2016), Swiss Cancer Research (KFS-02783-02-2011), the Swiss National Science Foundation (PDFMP3_141775), Kinderkrebshilfe Schweiz, the Federal Office of Public Health and the National Institute of Cancer Epidemiology and Registration. Slovenian Research Agency. The French Childhood Cancer Survivor Cohort is supported by the French Society of Childhood Cancer (SFCE), ARC foundation with the Pop-HaRC and CHART projects, the French National Cancer Institute (INCA) with Programme Hospitalier de Recherche Clinique, the Pfizer Foundation for childhood and adolescent health, the Ligue Nationale Contre le Cancer (LNCC), the Institut de Recherche en Santé Publique (IRESP) and the French 'Agence Nationale Pour la Recherche Scientifique' (Hope-Epi Project).

  • Disclaimer No funders played a role in the present study.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the 'Methods' section for further details.

  • Patient consent for publication Not required.

  • Ethics approval Medical ethical approval was obtained by each country (France, Hungary, Italy, the Netherlands, Switzerland, Slovenia, the UK).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Data will be available on request, an application of intent should be send to the corresponding author, she will send the application of intent to the appropriate comity.

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