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JMIR Res Protoc. 2021 Jan 27;10(1):e21256. doi: 10.2196/21256.

Metabolic Syndrome Parameters, Determinants, and Biomarkers in Adult Survivors of Childhood Cancer: Protocol for the Dutch Childhood Cancer Survivor Study on Metabolic Syndrome (Dutch LATER METS).

JMIR research protocols

Vincent Pluimakers, Marta Fiocco, Jenneke van Atteveld, Monique Hobbelink, Dorine Bresters, Eline Van Dulmen-den Broeder, Margriet Van der Heiden-van der Loo, Geert O Janssens, Leontien Kremer, Jacqueline Loonen, Marloes Louwerens, Helena Van der Pal, Cécile Ronckers, Hanneke Van Santen, Birgitta Versluys, Andrica De Vries, Marry Van den Heuvel-Eibrink, Sebastian Neggers

Affiliations

  1. Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
  2. Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.
  3. Mathematical Institute, Leiden University, Leiden, Netherlands.
  4. Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands.
  5. Department of Pediatric Oncology, Emma Children's Hospital/Amsterdam University Medical Center, Amsterdam, Netherlands.
  6. Dutch Childhood Oncology Group, Utrecht, Netherlands.
  7. Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands.
  8. Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.
  9. Department of Pediatric Oncology and Hematology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, Netherlands.
  10. Department of Pediatric Oncology/Hematology, Sophia Children's Hospital/Erasmus Medical Center, Rotterdam, Netherlands.
  11. Department of Endocrinology, Erasmus Medical Center, Rotterdam, Netherlands.

PMID: 32750002 PMCID: PMC7875697 DOI: 10.2196/21256

Abstract

BACKGROUND: Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia, and hypertension. These risk factors cluster together as metabolic syndrome and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis, and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no national cohort studies on the prevalence and determinants of metabolic syndrome in childhood cancer survivors, including biomarkers and genetic predisposition, are available.

OBJECTIVE: The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of metabolic syndrome and its separate components, and 2) the potential diagnostic and predictive value of additional biomarkers for surveillance of metabolic syndrome in the national cohort of adult long-term survivors of childhood cancer.

METHODS: This is a cross-sectional study based on recruitment of all survivors treated in the Netherlands between 1963 and 2002. Metabolic syndrome will be classified according to the definitions of the third Adult Treatment Panel Report of the National Cholesterol Education Program as well as the Joint Interim Statement and compared to reference data. Dual-energy x-ray absorptiometry scans were performed to assess body composition in more detail. The effect of patient characteristics, previous treatment, and genetic variation on the risk of metabolic syndrome will be assessed. The diagnostic and predictive value of novel biomarkers will be tested.

RESULTS: Patient accrual started in 2016 and lasted until April 2020. A total of 2380 survivors from 7 pediatric oncology hospitals have participated. From July 2020, biomarker testing, single nucleotide polymorphism analysis, and data analysis will be performed.

CONCLUSIONS: The Dutch LATER METS study will provide knowledge on clinical and genetic determinants of metabolic syndrome and the diagnostic value of biomarkers in childhood cancer survivors. The results of this study will be used to optimize surveillance guidelines for metabolic syndrome in survivors based on enhanced risk stratification and screening strategies. This will improve diagnosis of metabolic syndrome and prevent complications.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21256.

©Vincent Pluimakers, Marta Fiocco, Jenneke van Atteveld, Monique Hobbelink, Dorine Bresters, Eline Van Dulmen-den Broeder, Margriet Van der Heiden-van der Loo, Geert O Janssens, Leontien Kremer, Jacqueline Loonen, Marloes Louwerens, Helena Van der Pal, Cécile Ronckers, Hanneke Van Santen, Birgitta Versluys, Andrica De Vries, Marry Van den Heuvel-Eibrink, Sebastian Neggers. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 27.01.2021.

Keywords: Dutch Childhood Cancer Survivor Study; Dutch LATER METS; childhood cancer survivor; metabolic syndrome; methodology

References

  1. Lancet. 2017 Dec 9;390(10112):2569-2582 - PubMed
  2. Blood. 2011 Apr 28;117(17):4442-8 - PubMed
  3. Eur J Intern Med. 2016 Apr;29:3-8 - PubMed
  4. Nat Commun. 2017 Nov 28;8(1):1826 - PubMed
  5. Annu Rev Med. 2018 Jan 29;69:247-262 - PubMed
  6. J Am Coll Cardiol. 2005 Dec 6;46(11):1978-85 - PubMed
  7. Bioinformatics. 2003 Jan;19(1):149-50 - PubMed
  8. Eur J Cancer. 2014 Apr;50(6):1169-75 - PubMed
  9. Pediatr Blood Cancer. 2015 Nov;62(11):1992-9 - PubMed
  10. Eur J Endocrinol. 2013 May 07;168(6):905-12 - PubMed
  11. Eur J Cancer. 2013 Feb;49(3):668-75 - PubMed
  12. Circulation. 2002 Dec 17;106(25):3143-421 - PubMed
  13. Lancet Oncol. 2010 Feb;11(2):193-203 - PubMed
  14. J Clin Oncol. 2012 Nov 10;30(32):3991-7 - PubMed
  15. Crit Rev Oncol Hematol. 2019 Jan;133:129-141 - PubMed
  16. Nat Genet. 2016 Oct;48(10):1279-83 - PubMed
  17. Sci Rep. 2018 Aug 1;8(1):11529 - PubMed
  18. PLoS One. 2012;7(8):e43269 - PubMed
  19. J Clin Oncol. 2009 May 10;27(14):2328-38 - PubMed
  20. Pediatr Blood Cancer. 2014 Jan;61(1):53-67 - PubMed
  21. Biol Blood Marrow Transplant. 2018 Mar;24(3):622-626 - PubMed
  22. Int J Cancer. 2016 Jul 15;139(2):322-33 - PubMed
  23. Nat Genet. 2016 Oct;48(10):1284-1287 - PubMed
  24. Am J Clin Nutr. 2018 Jan 1;107(1):3-11 - PubMed
  25. Clin Endocrinol (Oxf). 2015 Jan;82(1):59-67 - PubMed
  26. Indian J Cancer. 2015 Apr-Jun;52(2):219-23 - PubMed
  27. Crit Rev Oncol Hematol. 2018 Jun;126:154-167 - PubMed
  28. Circulation. 2009 Oct 20;120(16):1640-5 - PubMed
  29. Bone Marrow Transplant. 2015 Nov;50(11):1438-44 - PubMed
  30. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7 - PubMed
  31. Arch Intern Med. 2009 Aug 10;169(15):1381-8 - PubMed
  32. Ann Oncol. 2013 Mar;24(3):749-55 - PubMed
  33. PLoS One. 2012;7(12):e52237 - PubMed
  34. Eur J Cancer. 2019 Mar;110:86-97 - PubMed
  35. JAMA. 2010 Jul 14;304(2):172-9 - PubMed
  36. Cancer. 2005 Apr 1;103(7):1457-67 - PubMed
  37. Diabetes Care. 1991 Mar;14(3):173-94 - PubMed
  38. Nat Protoc. 2010 Sep;5(9):1564-73 - PubMed
  39. Circulation. 2012 May 22;125(20):2469-78 - PubMed
  40. Bioinformatics. 2016 May 1;32(9):1423-6 - PubMed
  41. Eur J Endocrinol. 2017 Apr;176(4):R183-R203 - PubMed
  42. Pediatr Blood Cancer. 2013 Dec;60(12):1922-8 - PubMed
  43. Cancer. 2014 Sep 1;120(17):2742-50 - PubMed
  44. Cancer. 2015 Dec 1;121(23):4197-204 - PubMed
  45. Biol Blood Marrow Transplant. 2017 Mar;23(3):475-482 - PubMed
  46. J Clin Oncol. 2012 May 1;30(13):1429-37 - PubMed
  47. Cancer Epidemiol Biomarkers Prev. 2017 Dec;26(12):1705-1713 - PubMed
  48. J Clin Epidemiol. 2003 Dec;56(12):1163-9 - PubMed
  49. Cancer. 2015 Jun 15;121(12):2036-43 - PubMed
  50. Eur J Cancer. 2012 May;48(8):1159-66 - PubMed
  51. BMC Cancer. 2017 Nov 10;17(1):751 - PubMed
  52. Biol Blood Marrow Transplant. 2010 Dec;16(12):1674-81 - PubMed
  53. Eur Heart J. 2020 Jan 1;41(1):111-188 - PubMed
  54. J Clin Oncol. 2016 Sep 20;34(27):3240-7 - PubMed
  55. J Clin Oncol. 2013 Nov 1;31(31):3906-13 - PubMed
  56. Lancet Oncol. 2012 Oct;13(10):1002-10 - PubMed
  57. Diabetes. 1988 Dec;37(12):1595-607 - PubMed
  58. Haematologica. 2016 Dec;101(12):1603-1610 - PubMed
  59. Br J Haematol. 2014 May;165(3):364-74 - PubMed
  60. Metabolism. 2006 Nov;55(11):1546-50 - PubMed
  61. J Exp Clin Cancer Res. 2011 Jun 01;30:64 - PubMed
  62. Endocr Dev. 2009;15:1-24 - PubMed
  63. Eur Respir J. 2011 Jan;37(1):150-6 - PubMed
  64. Cochrane Database Syst Rev. 2019 Mar 11;3:CD008944 - PubMed
  65. Cancer. 2015 Jul 1;121(13):2262-70 - PubMed
  66. Eur J Prev Cardiol. 2015 Jun;22(6):762-70 - PubMed

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