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

Our plain-English summary of Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database, by A. Farioli, M. Ottone, A.G. Morganti, et al (Cancer Medicine, 2016).

The study

• Authors: A. Farioli, M. Ottone, A.G. Morganti, G. Compagnone, F. Romani, S. Cammelli, S. Mattioli, F.S. Violante
• Journal: Cancer Medicine
• Published: 2016;5(5):950-9
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

In plain English

This study used US cancer registry data (SEER, 1973 to 2012) to ask whether external beam radiotherapy (EBRT) for a first solid cancer was linked to later mesothelioma. The authors followed 935,637 adults who survived at least 5 years after their first cancer. They compared 341,688 people treated with EBRT with 593,949 who had no radiotherapy. No one's individual asbestos exposure was recorded, so the authors used each county's mesothelioma risk as a stand-in. There were 301 mesotheliomas: 265 pleural, 32 peritoneal and 4 at other or unknown sites. After adjustment, EBRT patients had a higher risk of mesothelioma at any site (hazard ratio 1.34, 95% CI 1.04 to 1.74) and of pleural mesothelioma (1.34, 1.01 to 1.77). Pleural risk was not higher with direct than with scattered radiation. For peritoneal mesothelioma, a raised estimate appeared only after direct irradiation, based on few cases. Forty years after diagnosis, the estimated cumulative incidence was 0.00032 without and 0.00055 with radiotherapy. The authors concluded that EBRT might be a determinant of mesothelioma but that its clinical impact is limited.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study using US SEER cancer registry data
• Who was studied: 935,637 adults (over 20) in US SEER registries with a first primary solid cancer at sites often treated with EBRT, diagnosed 1973 to 2012, who survived at least 5 years. Of these, 341,688 received EBRT and 593,949 received no radiotherapy. Follow-up started 5 years after diagnosis and was stopped at age 85.
• Exposure: External beam radiotherapy (alone or with other radiotherapy) as initial treatment, compared with no radiotherapy. For site-specific analyses, the dose to the pleura or peritoneum was classed as scattered or direct according to where the first cancer was located. Asbestos exposure was not measured individually. As a proxy, the authors used the relative risk of primary mesothelioma among males in the county of residence.
• Main results:
  • 301 mesotheliomas occurred in the cohort: 265 pleural, 32 peritoneal and 4 at other or unknown sites.
  • Mesothelioma at any site, EBRT patients compared with nonirradiated patients, all latency periods: fully adjusted HR 1.34, 95% CI 1.04 to 1.74.
  • Mesothelioma at any site, latency of more than 10 years: fully adjusted HR 1.58, 95% CI 1.10 to 2.26.
  • Pleural mesothelioma, EBRT patients compared with nonirradiated patients: fully adjusted HR 1.34, 95% CI 1.01 to 1.77.
  • Pleural mesothelioma by dose: scattered irradiation fully adjusted HR 1.38 (95% CI 1.01 to 1.89); direct irradiation HR 1.23 (95% CI 0.77 to 1.96). The authors reported no important difference between doses.
  • Pleural mesothelioma, latency of more than 10 years: fully adjusted HR for EBRT 1.49, 95% CI 1.00 to 2.21.
  • Peritoneal mesothelioma after direct peritoneal irradiation (10 cases): age- and sex-adjusted HR 2.20, 95% CI 0.99 to 4.88. Fully adjusted estimates were not calculated because there were too few cases.
  • Peritoneal mesothelioma after direct irradiation, latency of more than 10 years (6 cases): HR 3.28, 95% CI 1.14 to 9.43.
  • Competing-risks subhazard ratios were lower than the cause-specific HRs. The authors read this as a limited clinical impact because of the high risk of death or other cancers.
  • Cumulative incidence of mesothelioma after 40 years of observation: 0.00032 in nonirradiated patients and 0.00055 in irradiated patients.
  • The county asbestos proxy was strongly linked to mesothelioma. Compared with counties where the relative risk was below 0.67, HRs ranged from 2.11 (relative risk 0.67 to 0.90) to 5.60 (relative risk 1.50 or more).
• The authors' conclusion: The authors concluded that exposure to ionizing radiation, in particular EBRT, might be a determinant of mesothelioma. They found that longer latency periods were associated with higher relative risks and that the dose-response relationship seemed nonlinear. They also concluded that the clinical impact of secondary mesothelioma after EBRT for a primary solid cancer is limited.
• Limitations the authors state:
  • Information on potential confounders was limited, and asbestos exposure could not be controlled directly; only a county-level proxy was available.
  • Possible detection bias.
  • Possible confounding by indication, meaning differences linked to the type of first cancer.
  • EBRT exposure may be wrongly recorded in register data. The authors expected this to bias estimates toward no effect.
  • Very long latency periods could not be studied: only eleven secondary mesotheliomas occurred more than 20 years after the first diagnosis. The study therefore informs only on latencies under 20 years.
  • With few peritoneal cases, the large difference between the scattered and direct radiation estimates for peritoneal mesothelioma could be due to chance.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, SEER, Peritoneal Mesothelioma, Epidemiology, Relative Risk, Asbestos Exposure, Hazard Ratio, Dose-response relationship.

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