Radiation Exposure Assessment in Late Effects Studies: Overview of Available Methods and Design/Rationale of the DCOG Later Dosimetry Research Project

Berthe Aleman, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital 
William F Anderson, BB/DCEG/NCI 
Dorine Bresters, Leiden University Medical Center, Leiden 
Huib N. Caron, Emma Children's Hospital/ AMC University Medical Center Amsterdam 
Wil Dolsma, Groningen University Medical Center 
*Judith L. Kok, DCOG LATER/ Emma Children's Hospital/ AMC 
Leontien C. Kremer, Emma Children's Hospital/ AMC Univeristy Medical Center Amsterdam 
Jacqueline Loonen, Radboud University Nijmegen Medical Center, Nijmegen 
Cecile M. Ronckers, DCOG LATER/ Emma Children's Hospital/ AMC 
Wim Tissing, Groningen University Medical Center 
Marry M. van den Heuvel-Eibrink, Erasmus MC-Sophia Children's Hospital Rotterdam 
Irma W.M. van Dijk, Academic Medical Center, Amsterdam 
Eline van Dulmen-den Broeder, VU University Medical Center, Amsterdam 
Flora E. van Leeuwen, Netherlands Cancer Institute, Amsterdam 
Brigitta Versluys, Wilhelmina Children's Hospital, Utrecht 

Keywords: Radiation dosimetry, Late effects, Childhood Cancer Survivors

Background Anticancer therapy is associated with adverse health effects. We are conducting a series of retrospective studies on medically assessed adverse events among long-term childhood cancer survivors in the Dutch DCOG LATER cohort, of whom ~3000 had radiotherapy between 1963 and 2001. We aim to (1) provide a review of available methods to quantify radiation effects in existing late effects studies and (2) describe rationale for and design of our Dosimetry Research Program.

Methods We conducted a review of available methods employed in studies on late effects of radiotherapy, including study design (i.e., cohort, case-control, patient series, etc.), methods to quantify radiation dose (patient chart based, type of dosimetry method employed, etc.), and the statistical/biological/mathematical models applied to derive quantitative risk estimates, including an assessment of pros and cons.

Results The literature review results will be summarized in a concise table. Cohort-wide data collection for absorbed radiation doses for multiple organs-at-risk is warranted and feasible and should allow for (a) valid comparison of patients treated for different cancer types at different ages and affecting different body parts; and (b) investigation of the potential contribution of volume and fractionation to risk estimates, important parameters according to radiobiology, yet rarely studied epidemiologically. We propose to construct a radiation exposure matrix, for homogeneous patient groups treated with similar radiotherapy, with measures of: organ-in-beam (y/n); absorbed dose; volume; and fractionation; for relevant organs, where feasible. This is probably not possible for any combination of past therapy and organ-at-risk. Nevertheless, this effort will serve DCOG LATER late effects studies and will allow for a descriptive analysis of radiotherapy methods in pediatric oncology in the past 50 years. Conclusions The DCOG LATER Dosimetry Research Program is unique in scope and will provide a solid basis for current and future retrospective quantitative studies on radiotherapy-related adverse events.