Radiotherapy-Related Dose and Irradiated Volume Effects on Breast Cancer Risk Among Hodgkin Lymphoma Survivors

Sander Roberti, Flora E. van Leeuwen, Cécile M. Ronckers, Inge M. Krul, Florent de Vathaire, Cristina Veres, Ibrahima Diallo, Cécile P.M. Janus, Berthe M.P. Aleman, Nicola S. Russell, Michael Hauptmann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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BACKGROUND: Breast cancer (BC) risk is increased among Hodgkin lymphoma (HL) survivors treated with chest radiotherapy. Case-control studies showed a linear radiation dose-response relationship for estimated dose to the breast tumor location. However, these relative risks cannot be used for absolute risk prediction of BC anywhere in the breasts. Furthermore, the independent and joint effects of radiation dose and irradiated volumes are unclear. Therefore, we examined the effects of mean breast dose and various dose-volume parameters on BC risk in HL patients. METHODS: We conducted a nested case-control study of BC among 5-year HL survivors (173 case patients, 464 matched control patients). Dose-volume histograms were obtained from reconstructed voxel-based 3-dimensional dose distributions. Summary parameters of dose-volume histograms were studied next to mean and median breast dose, Gini index, and the new dose metric mean absolute difference of dose, using categorical and linear excess odds ratio (EOR) models. Interactions between dose-volume parameters and mean dose were also examined. RESULTS: Statistically significant linear dose-response relationships were observed for mean breast dose (EOR per Gy = 0.19, 95% confidence interval [CI] = 0.05 to 1.06) and median dose (EOR/Gy = 0.06, 95% CI = 0.02 to 0.19), with no statistically significant curvature. All metrics except Gini and mean absolute difference were positively correlated with each other. These metrics all showed similar patterns of dose-response that were no longer statistically significant when adjusting for mean dose. No statistically significant modification of the effect of mean dose was observed. CONCLUSION: Mean breast dose predicts subsequent BC risk in long-term HL survivors.

Original languageEnglish
Pages (from-to)1270-1278
Number of pages9
JournalJournal of the National Cancer Institute
Issue number9
Publication statusPublished - 1 Sept 2022

Bibliographical note

This work was supported by the Dutch Cancer Society (grant number KWF10004).

Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press.


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