Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma

Our plain-English summary of Therapeutic radiation for lymphoma and risk of second primary malignant mesothelioma, by E.T. Chang, E.C. Lau, F.S. Mowat, et al (Cancer Causes & Control, 2017).

The study

• Authors: E.T. Chang, E.C. Lau, F.S. Mowat, M.J. Teta
• Journal: Cancer Causes & Control
• Published: 2017;28(9):971-979
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

In plain English

This population-based cohort study used U.S. SEER cancer registry data. The authors followed 47,219 Hodgkin lymphoma and 252,090 non-Hodgkin lymphoma patients diagnosed 1973 to 2014. They compared patients with and without beam radiotherapy during first treatment. Among all irradiated patients, 28 mesotheliomas occurred against 15.73 expected (standardized incidence ratio 1.78, 95% CI 1.18–2.58). Non-irradiated patients had 59 against 51.00 expected, not a significant increase. The increase was significant for irradiated Hodgkin patients (SIR 4.37, 95% CI 2.00–8.31) but not for irradiated non-Hodgkin patients (SIR 1.39, 95% CI 0.84–2.20). After adjusting for age, sex, race, lymphoma type, diagnosis period and nodal status, radiotherapy was associated with a relative risk of 1.64 (95% CI 1.05–2.57). Within subgroups, radiotherapy versus none gave a relative risk of 4.05 (95% CI 1.65–9.95) at 10 or more years after diagnosis and 2.59 (95% CI 1.18–5.69) for diagnosis before 1995. The authors concluded the radiotherapy-related increase was independent of several patient and disease characteristics. They noted small case numbers and no radiation dose data. They lacked asbestos exposure information but considered asbestos unlikely to explain the findings.

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: Population-based cohort study (brief report) using U.S. SEER cancer registry data, with standardized incidence ratios and competing-risks survival analysis
• Who was studied: 47,219 Hodgkin lymphoma patients (19,538 irradiated) and 252,090 non-Hodgkin lymphoma patients (52,454 irradiated), diagnosed 1973 to 2014 in the U.S. SEER 18 registries and followed through 31 December 2014
• Exposure: Beam radiotherapy given during the first course of lymphoma treatment. No information was available on later treatment, radiation dose, or asbestos exposure.
• Main results:
  • Both lymphoma types combined, irradiated patients: 28 mesothelioma cases observed vs. 15.73 expected (SIR = 1.78, 95% CI 1.18–2.58). Non-irradiated patients: 59 observed vs. 51.00 expected (SIR = 1.16, 95% CI 0.89–1.50), not a significant increase.
  • Hodgkin lymphoma patients treated with radiotherapy: 9 cases observed vs. 2.06 expected (SIR = 4.37, 95% CI 2.00–8.31), a statistically significant increase. Hodgkin patients without radiotherapy: 5 observed vs. 2.94 expected (SIR = 1.70, 95% CI 0.55–3.97).
  • Non-Hodgkin lymphoma patients treated with radiotherapy: 19 cases observed vs. 13.67 expected (SIR = 1.39, 95% CI 0.84–2.20), elevated but not statistically significant.
  • After adjustment for age, sex, race, lymphoma type, year of diagnosis and nodal status, radiotherapy was associated with mesothelioma risk in all lymphoma patients (RR = 1.64, 95% CI 1.05–2.57).
  • The radiotherapy versus no radiotherapy association was stronger with longer latency: RR = 2.32 (95% CI 1.29–4.17) with latency of at least 5 years, and RR = 4.05 (95% CI 1.65–9.95, 21 cases) with latency of at least 10 years. With latency under 10 years, the RR was 1.13 (95% CI 0.61–2.09, 66 cases).
  • Radiotherapy versus no radiotherapy, within diagnosis period: for patients diagnosed before 1995 (23 mesothelioma cases) the RR was 2.59 (95% CI 1.18–5.69). For those diagnosed in 1995 or later (64 cases) it was 1.32 (95% CI 0.73–2.38).
  • Risk after radiotherapy appeared higher for patients diagnosed before age 40 (RR 2.88, 95% CI 0.67–12.30). This was not statistically significant and rested on 11 cases.
  • Among irradiated lymphoma patients, the absolute excess risk ranged between 0.14 and 0.25 excess mesothelioma cases per 10,000 person-years.
• The authors' conclusion: The authors concluded that 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.
• Limitations the authors state:
  • Mesothelioma is rare and average follow-up was relatively short, so case numbers were small, especially in subgroups, which limited statistical power.
  • Some radiotherapy, especially outside hospitals in recent years, may have been missed by SEER registries.
  • SEER lacks detailed information on radiation doses and treatment fields, so detailed dose-response analysis was not possible.
  • There was no information on patients' occupational history or asbestos exposure. The authors argued that asbestos was unlikely to confound the radiotherapy association.
  • Patients who moved out of the SEER area may have had later mesotheliomas missed.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Epidemiology, Standardized Incidence Ratio (SIR), confidence interval, Relative Risk, Latency.

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