Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database

Abstract

We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5 years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01-1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies ≥10 years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited.

Keywords: Cohort study; SEER program; dose-response relationship, radiation; mesothelioma; radiation-induced malignancies; radiotherapy.

Figure 1

Flowchart of the study population. Patients affected by primary cancer followed up for malignant mesothelioma. EBRT, external beam radiotherapy.

Figure 2

Cumulative incidence function of mesothelioma in any site; estimates from flexible parametric survival models for competing risks. *Cumulative incidence functions adjusted by age (60 years, mean value), sex (female, modal value), race (white, modal value), year of primary cancer diagnosis (1996, median value), primary cancer surgery (performed, modal value), and county's mesothelioma relative risk (1.01, mean value).