We would like to thank Brown et al. for bringing to our attention their important work, which demonstrated an association between radiotherapy and mesothelioma in testicular cancer survivors.1 Both in their study as well in our cohort of non-Hodgkin lymphoma survivors,2 we observed an association between radiotherapy and a subsequent diagnosis of mesothelioma. Prophylactic supradiaphragmatic radiotherapy is no longer the standard of care for patients with locoregional germ cell testicular cancer.

Brown et al. also reveal new data from a Scandinavian population-based study showing an increased risk of mesothelioma in breast cancer survivors treated with radiotherapy, with the greatest risk observed in patients treated prior to 1970. Although the details of their study population and radiotherapy treatment techniques were not revealed in their correspondence, we attempted to corroborate their findings using the U.S. Surveillance, Epidemiology, and End Results (SEER) program population database. There were 328,878 patients diagnosed with in situ, localized, or regional breast cancer between 1973 and 2002 who were identified. A total of 32 patients subsequently developed mesothelioma, and the standardized incidence ratio was similar to the endemic population risk (observed/expected [O/E] ratio, 0.82; 95% confidence interval [95% CI], 0.56–1.15). When examining only those patients who survived ≥10 years from the time of their breast cancer diagnosis, those who had received radiotherapy were found to have a similar risk to the nonirradiated cohort (O/E ratio, 1.29; 95% CI, 0.26–3.76 for the 28,595 radiotherapy patients; and O/E ratio, 0.82; 95% CI, 0.35-1.62 for the 83,869 nonirradiated patients). Neither of the groups of patients surviving for ≥10 years was found to have a significantly elevated risk compared with the referent U.S. population.

Brown et al. had a longer follow-up period. Patients were followed in their cancer registry since 1943 whereas the SEER program we evaluated reported data from 1973 onward. As Brown et al. indicated, radiotherapy techniques have markedly improved since the pre-1970s era. In the pre-1970s era (prior to the widespread adoption of megavoltage linear accelerators), patients may have received maximum and integral doses to the pleural surface that were greater than those using modern radiotherapy techniques due to nonstandardized dose/fractionation regimens, the variability and lower peak energies from “historic” radiotherapy equipment, less rigorous quality assurance, an inability to account for tissue inhomogeneities, and a lack of computerized treatment planning.

Travis et al. elegantly demonstrated a radiotherapy dose response for tumor induction in patients with Hodgkin disease and this may also be relevant for mesothelioma.3 Population-based studies such as these are important to evaluate treatment-induced late toxicities. With continued studies, we can refine our treatments to make them safer for patients.


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Jonathan D. Tward MD, PhD*, Dennis C. Shrieve MD, PhD*, David K. Gaffney MD, PhD*, * Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah.