Measuring childhood cancer late effects: evidence of a healthy survivor effect

  • Peter Haubjerg Asdahl
  • Rohit Priyadarshi Ojha
  • Jeanette Falck Winther
  • Anna Sällfors Holmqvist
  • Sofie de Fine Licht
  • Thorgerdur Gudmundsdottir
  • Laura Madanat-Harjuoja
  • Laufey Tryggvadottir
  • Klaus Kaae Andersen
  • Henrik Hasle
  • on behalf of the ALiCCS study group
CANCER
  • 76 Downloads

Abstract

Introduction

Given considerable focus on health outcomes among childhood cancer survivors, we aimed to explore whether survivor bias is apparent during long-term follow-up of childhood cancer survivors.

Methods

We identified all 1-year survivors of cancer diagnosed before 20 years of age in Denmark, Finland, Iceland, and Sweden. From the general population, we randomly sampled a comparison cohort. Study individuals were followed for hospitalizations for diseases of the gastroenterological tract, endocrine system, cardiovascular system, or urinary tract from the start of the cancer registries to 2010. We estimated cumulative incidence with death as competing risk and used threshold regression to compare the hazards of the diseases of interest at ages 20, 40, 60, and 75 years.

Results

Our study included 27,007 one-year survivors of childhood cancer and 165,620 individuals from the general population. The cumulative incidence of all four outcomes was higher for childhood cancer survivors during early adulthood, but for three outcomes, the cumulative incidence was higher for the general population after age 55 years. The hazard ratios (HRs) decreased for all outcomes with increasing age, and for two of the outcomes, the hazards were higher for the general population at older ages (endocrine diseases: age-specific HRs = 3.0, 1.4, 1.0, 0.87; Cardiovascular diseases: age-specific HRs = 4.1, 1.4, 0.97, 0.84).

Conclusions

Our findings provide empirical evidence that survivor bias attenuates measures of association when comparing survivors with the general population. The design and analysis of studies among childhood cancer survivors, particularly as this population attains older ages, should account for survivor bias to avoid misinterpreting estimates of disease burden.

Keywords

Survivor bias Healthy survivor effect Cancer survivorship Childhood cancer Competing risk Late effects 

Notes

Acknowledgements

We thank Andrea Bautz and Anja Krøyer Kristoffersen for their for tremendous contribution to data management and members of the ALiCCS board Catherine Rechnitzer, Kirsi Jahnukainen, Jørgen H. Olsen, Finn Wesenberg, and Lars Hjorth for their valuable guidance and discussions. The study was supported by Grant 09-066899 from the Danish Council for Strategic Research and by a grant from the Danish Child Cancer Foundation. All authors have approved the final manuscript. Peter H. Asdahl had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Peter Haubjerg Asdahl
    • 1
    • 2
  • Rohit Priyadarshi Ojha
    • 3
  • Jeanette Falck Winther
    • 4
  • Anna Sällfors Holmqvist
    • 6
  • Sofie de Fine Licht
    • 4
  • Thorgerdur Gudmundsdottir
    • 4
    • 5
  • Laura Madanat-Harjuoja
    • 7
  • Laufey Tryggvadottir
    • 8
    • 9
  • Klaus Kaae Andersen
    • 4
  • Henrik Hasle
    • 1
  • on behalf of the ALiCCS study group
  1. 1.Department of PediatricsAarhus University HospitalÅrhusDenmark
  2. 2.Department of HematologyHospital Unit Jutland WestHolstebroDenmark
  3. 3.Center for Outcomes ResearchJPS Health NetworkFort WorthUSA
  4. 4.Danish Cancer Society Research CenterCopenhagenDenmark
  5. 5.Children’s HospitalLandspitali University HospitalReykjavíkIceland
  6. 6.Pediatric Hematology and OncologySkåne University HospitalLundSweden
  7. 7.Finnish Cancer RegistryHelsinkiFinland
  8. 8.Faculty of MedicineUniversity of IcelandReykjavíkIceland
  9. 9.Icelandic Cancer RegistryReykjavíkIceland

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