Elsevier

The Lancet Oncology

Volume 12, Issue 4, April 2011, Pages 353-360
The Lancet Oncology

Articles
Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries

https://doi.org/10.1016/S1470-2045(11)70061-4Get rights and content

Summary

Background

Improvements in cancer survival have made the long-term risks from treatments more important, including the risk of developing a second cancer after radiotherapy. We aimed to estimate the proportion of second cancers attributable to radiotherapy in adults with data from the US Surveillance, Epidemiology and End Results (SEER) cancer registries.

Methods

We used nine of the SEER registries to systematically analyse 15 cancer sites that are routinely treated with radiotherapy (oral and pharynx, salivary gland, rectum, anus, larynx, lung, soft tissue, female breast, cervix, endometrial, prostate, testes, eye and orbit, brain and CNS, and thyroid). The cohort we studied was composed of patients aged 20 years or older who were diagnosed with a first primary invasive solid cancer reported in the SEER registries between Jan 1, 1973, and Dec 31, 2002. Relative risks (RRs) for second cancer in patients treated with radiotherapy versus patients not treated with radiotherapy were estimated with Poisson regression adjusted for age, stage, and other potential confounders.

Findings

647 672 cancer patients who were 5-year survivors were followed up for a mean 12 years (SD 4·5, range 5–34); 60 271 (9%) developed a second solid cancer. For each of the first cancer sites the RR of developing a second cancer associated with radiotherapy exceeded 1, and varied from 1·08 (95% CI 0·79–1·46) after cancers of the eye and orbit to 1·43 (1·13–1·84) after cancer of the testes. In general, the RR was highest for organs that typically received greater than 5 Gy, decreased with increasing age at diagnosis, and increased with time since diagnosis. We estimated a total of 3266 (2862–3670) excess second solid cancers that could be related to radiotherapy, that is 8% (7–9) of the total in all radiotherapy patients (≥1 year survivors) and five excess cancers per 1000 patients treated with radiotherapy by 15 years after diagnosis.

Interpretation

A relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors, such as lifestyle or genetics.

Funding

US National Cancer Institute.

Introduction

Radiotherapy reduces the risk of cancer recurrence, promotes tumour control, and improves survival.1 However, with improved survival, the long-term risks from radiotherapy—including the risk of developing a second cancer—become more important. Subsequent malignancies in cancer survivors now constitute 18% of all cancer diagnoses in the US Surveillance, Epidemiology and End Results (SEER) cancer registries, making them the third most common cancer diagnosis. Compared with the general population, cancer survivors have an approximately 14% higher rate of cancer.2 These greater risks are probably the result of a combination of shared lifestyle and genetic factors, as well as the treatment for the first cancer. Although many studies have shown an association between radiotherapy and the risk of developing a second cancer, it is not known what proportion of second cancers might be related to radiotherapy. In two recent studies3, 4 we used the SEER cancer registries to develop some of the first estimates of the attributable risk for specific first cancers, and we concluded that about 5–6% of second solid cancers after breast cancer3 and 11% after endometrial cancer4 might be related to radiotherapy. Here, we extend this assessment to do a comprehensive and systematic analysis of all first solid cancer sites in adults that are routinely treated with radiotherapy with data from the SEER registries. The large population covered by these registries, combined with more than three decades of follow-up, enables long-term detailed assessment of the patterns of risk after radiotherapy.

Section snippets

Population and follow-up

The cohort was composed of patients aged 20 years or older who were diagnosed with a first primary invasive solid cancer reported to one of nine SEER registries (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco–Oakland, Seattle–Puget Sound, and Utah) between Jan 1, 1973, and Dec 31, 2002. We included 15 solid-cancer sites that are routinely treated with radiotherapy (oral and pharynx, salivary gland, rectum, anus, larynx, lung, soft tissue, female breast, cervix,

Results

There were 647 672 adult cancer patients who survived for 5 years or longer in the cohort, followed up for a mean 12 years (SD 4·5, range 5–34). The proportion of patients who received radiotherapy as part of their initial cancer treatment varied from 23% for non-small-cell lung cancer to 79% for testicular seminomas (table 1). Patterns of radiotherapy varied across the first cancer sites, but receipt of radiotherapy was slightly less common in the oldest patients (age 75–79 years) for most

Discussion

Our results suggest that about 8% (95% CI 7–9) of second solid cancers might be related to radiotherapy treatment for the first cancer. This figure varied according to first cancer site, from 4% for cancers of the eye or orbit to 24% for cancer of the testes. Higher attributable risks were probably because of younger age at treatment, larger treatment fields, and the organs located in those fields. The RRs generally decreased with increasing age, and increased with increasing time from

References (37)

  • DL Preston et al.

    Solid cancer incidence in atomic bomb survivors: 1958–1998

    Radiat Res

    (2007)
  • M Stovall et al.

    Dose reconstruction for therapeutic and diagnostic radiation exposures: use in epidemiological studies

    Radiat Res

    (2006)
  • CJ Edmonds et al.

    The long-term hazards of the treatment of thyroid cancer with radioiodine

    Br J Radiol

    (1986)
  • H Remy et al.

    131I effective half-life and dosimetry in thyroid cancer patients

    J Nucl Med

    (2008)
  • KS Kolbert et al.

    Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software

    J Nucl Med

    (2007)
  • RE Curtis et al.

    Methods

  • Y Yasui et al.

    A methodological issue in the analysis of second-primary cancer incidence in long-term survivors of childhood cancers

    Am J Epidemiol

    (2003)
  • M Clarke et al.

    Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials

    Lancet

    (2005)
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