Self-administered questionnaire assessing childhood cancer treatments and associated risks for adverse health outcomes - The KiKme study

Lara Kim Brackmann; Ronja Foraita; Heike Schwarz; Alicia Poplawski; Thomas Hankeln; Danuta Galetzka; Sebastian Zahnreich; Claudia Spix; Maria Blettner; Heinz Schmidberger; Manuela Marron

doi:10.3389/fonc.2023.1150629

Self-administered questionnaire assessing childhood cancer treatments and associated risks for adverse health outcomes - The KiKme study

Front Oncol. 2023 Apr 14:13:1150629. doi: 10.3389/fonc.2023.1150629. eCollection 2023.

Authors

Affiliations

¹ Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
² Faculty of Mathematics and Computer Science, University of Bremen, Bremen, Germany.
³ Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
⁴ Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁵ Institute of Organismic and Molecular Evolution, Molecular Genetics and Genome Analysis, Johannes Gutenberg University, Mainz, Germany.
⁶ Department of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁷ German Childhood Cancer Registry, Division of Childhood Cancer Epidemiology (EpiKiK), Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Abstract

Background: Childhood cancer survivors (CCS) are at particularly high risk for therapy-related late sequelae, with secondary primary neoplasms (SPN) being the most detrimental. Since there is no standardized questionnaire for retrospective assessment of associations between prior cancer treatments and late health effects, we developed a self-administered questionnaire and validated it in a cohort of CCS.

Methods: CCS of a first primary neoplasm (FPN, N=340) only or with a subsequent SPN (N=101) were asked whether they had received cancer therapies. Self-reports were compared to participants' medical records on cancer therapies from hospitals and clinical studies (N=242). Cohen's Kappa (κ) was used to measure their agreement and logistic regression was used to identify factors influencing the concordance. Associations between exposure to cancer therapies and late health effects (overweight/obesity, diseases of the lipid metabolism and the thyroid gland, cardiovascular diseases, occurrence of SPN) were analyzed in all participants by applying generalized linear mixed models to calculate odds ratios (OR) and 95% confidence intervals (95%CI).

Results: For CCS of SPN, a perfect agreement was found between self-reports and medical records for chemotherapy (CT, κ=1.0) while the accordance for radiotherapy (RT) was lower but still substantial (κ=0.8). For the CCS of FPN the accordance was less precise (CT: κ=0.7, RT: κ=0.3). Cancer status, tumors of the central nervous system, sex, age at recruitment, vocational training, follow-up time, and comorbidities had no impact on agreement. CCS with exposure to CT were found to be less often overweight or obese compared to those without CT (OR=0.6 (95%CI 0.39; 0.91)). However, they were found to suffer more likely from thyroid diseases excluding thyroid cancers (OR=9.91 (95%CI 4.0; 24.57)) and hypercholesterolemia (OR=4.45 (95%CI 1.5; 13.23)). All other analyses did not show an association.

Conclusion: Our new questionnaire proved reliable for retrospective assessment of exposure to CT and RT in CCS of SPN. For the CCS of FPN, self-reported RT was very imprecise and should not be used for further analyses. We revealed an association between late health outcomes occurring as hypercholesterolemia and thyroid diseases, excluding thyroid cancer, and the use of CT for the treatment of childhood cancer.

Keywords: body mass index - BMI; chemotherapy; childhood cancer survivors (CCS); lipid metabolism; radiotherapy; second malignancies; thyroid diseases; validation.

Grants and funding

This work was supported by the Federal Ministry of Education and Research in Germany (Grants 02NUK016A, 02NUK042A, 02NUK042B, 02NUK042C, and 02NUK042D). The study is funded among other research projects as part of the ISIMEP (Intrinsic radiation sensitivity: Identification, mechanisms and epidemiology, principal investigator: MB) and the ISIBELa (Intrinsic radiation sensitivity: Identification of biological and epidemiological long-term effects, principal investigator: MB and HSchm) consortium.