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