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Measuring childhood cancer late effects: evidence of a healthy survivor effect
Authors:Peter?Haubjerg?Asdahl  Rohit?Priyadarshi?Ojha  Jeanette?Falck?Winther  Anna?S?llfors?Holmqvist  Sofie?de?Fine Licht  Thorgerdur?Gudmundsdottir  Laura?Madanat-Harjuoja  Laufey?Tryggvadottir  Klaus?Kaae?Andersen  Henrik?Hasle
Institution:1.Department of Pediatrics,Aarhus University Hospital,?rhus,Denmark;2.Department of Hematology,Hospital Unit Jutland West,Holstebro,Denmark;3.Center for Outcomes Research,JPS Health Network,Fort Worth,USA;4.Danish Cancer Society Research Center,Copenhagen,Denmark;5.Children’s Hospital,Landspitali University Hospital,Reykjavík,Iceland;6.Pediatric Hematology and Oncology,Sk?ne University Hospital,Lund,Sweden;7.Finnish Cancer Registry,Helsinki,Finland;8.Faculty of Medicine,University of Iceland,Reykjavík,Iceland;9.Icelandic Cancer Registry,Reykjavík,Iceland
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:
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