Purpose: In epidemiologic research radiation-associated late effects after childhood cancer are usually analyzed without considering fraction dose. According to radiobiological principles, fraction dose is an important determinant of late effects. We aim to provide the rationale for using equivalent dose in 2-Gy fractions (EQD2(α/β)) as the measure of choice rather than total physical dose as prescribed according to the clinical protocol.
Methods: Between 1966 and 1996, 597 (43.8%) children in our cohort of 1,362 5-year childhood cancer survivors (CCS) received radiotherapy before the age of 18 years as part of their primary cancer treatment. Detailed information from individual patients' charts was collected and physical doses were converted into the EQD2(α/β), which includes total dose, fraction dose, and the tissue-specific α/β ratio. The use of EQD2(α/β) is illustrated in examples studies describing different analyses using EQD2(α/β) and physical dose.
Results: Radiotherapy information was obtained for 510 (85.4%) CCS. Multivariable analyses rendered different risk estimates for total body irradiation in EQD2(α/β)-based vs. physical-dose-based models. For other radiotherapy regimens, risk estimates were similar.
Conclusions: Using the total physical dose is not adequate for advanced analyses of radiation-associated late effects in CCS. Therefore, it is advised that for future studies the EQD2(α/β) is used, because the EQD2(α/β) incorporates the fraction dose, and the tissue-specific α/β ratio. Furthermore, it enables comparisons across fractionation regimens and allows for summing doses delivered by various contemporary and future radiation modalities.
Implications for cancer survivors: Risk estimates of radiation-associated side effects expressed in EQD2(α/β) provide more precise, clinically relevant information for cancer survivor screening guidelines.