Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma



This large, population-based U.S. study of lymphoma patients followed for up to four decades enables detailed analysis of second primary mesothelioma risk after radiotherapy.


U.S. Surveillance, Epidemiology, and End Results data were used to identify second primary mesothelioma among patients diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) between 1973 and 2014. Standardized incidence ratios (SIRs) were calculated by radiotherapy. Multivariate adjusted associations were examined using competing risks survival analysis.


Among 47,219 HL patients (19,538 irradiated) and 252,090 NHL patients (52,454 irradiated), second primary mesothelioma developed among 28 lymphoma patients who received radiotherapy and 59 who did not. Mesothelioma risk was increased among HL and NHL patients treated with radiotherapy [SIR = 1.78, 95% confidence interval (CI) 1.18–2.58], but not without radiotherapy. After multivariate adjustment, radiotherapy was associated with increased mesothelioma risk (relative risk = 1.64, 95% CI 1.05–2.57), especially in lymphoma patients diagnosed before 1995 and after a latency of at least 10 years, and apparently with younger age at diagnosis.


The increase in second primary mesothelioma risk following radiotherapy for lymphoma is independent of several patient and disease characteristics, and is higher with earlier treatment era and longer latency.

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We thank Dr. Karin Ekström Smedby (Karolinska University Hospital) for her expert guidance on clinical issues. M. Jane Teta and Fionna Mowat have served as expert witnesses and consultants, and Ellen Chang has provided litigation support, involving potential health hazards associated with asbestos in various consumer products. Partial funding for the analyses performed was provided by counsel for CenturyLink, who are involved with asbestos-related litigation and retained M. Jane Teta. This manuscript is exclusively the work product of the authors, and the results and the manuscript were not reviewed or discussed by the study sponsors prior to journal submission.

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Correspondence to Ellen T. Chang.

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Chang, E.T., Lau, E.C., Mowat, F.S. et al. Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma. Cancer Causes Control 28, 971–979 (2017).

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  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
  • Mesothelioma
  • Radiotherapy
  • Epidemiology
  • SEER Program