A Methodological Issue in the Analysis of Second-Primary Cancer Incidence in Long-Term Survivors of Childhood Cancers

Academic Article


  • Survival of childhood cancer patients has increased remarkably in the last several decades due to therapeutic improvements. Associated with this progress is the emerging need to accurately assess/minimize late effects of cancer therapy in long-term survivors. This paper considers a methodological issue in assessing the risk of second-primary malignant neoplasms, a major late effect of concern, using second-primary female breast cancer as an example. In the assessment of second-primary malignant neoplasm risk, attained age is a critical factor that must be taken into account. Even with follow-up of decades, childhood-cancer survivors are still at relatively young ages for developing adult-onset diseases. Attained ages at follow-up, however, modify cancer risk considerably; for example, in the general population, women aged 40 years have about fivefold increased breast cancer risk compared with women aged 30 years. A failure to account for the natural age-associated increase of risk could alter, or even reverse, analytical conclusions. This problem was studied empirically by both descriptive and regression analyses of two major studies of long-term childhood-cancer survivors, the Childhood Cancer Survivor Study (1975-1999) and the Late Effects Study Group (1955-1994). These showed appreciable differences in the analytical results by not accounting for the natural age-associated increase of risk illustrating a significant impact of this methodological issue on study conclusions.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Yasui Y; Liu Y; Neglia JP; Friedman DL; Bhatia S; Meadows AT; Diller LR; Mertens AC; Whitton J; Robison LL
  • Start Page

  • 1108
  • End Page

  • 1113
  • Volume

  • 158
  • Issue

  • 11