It appears that only 8% of second solid cancers can be attributed to radiotherapy for a first cancer, according to a report published online March 30 in the Lancet.
This figure varies somewhat according to the site of the first solid tumor, with the lowest attributable risk (4%) in cancers of the eye or orbit and the highest attributable risk (24%) in cancers of the testes.
Given that only a small proportion of second cancers among adult survivors are likely to be related to radiotherapy, it follows that most second cancers arise from other causes, such as genetics or lifestyle factors, said Amy Berrington de Gonzalez, D.Phil., of the National Cancer Institute, and her associates.
"These findings can be used by physicians and patients to put the risk of radiation-related cancer into perspective when compared with the probable benefits of treatment," the researchers noted.
Many studies have shown an association between receiving radiotherapy for a first solid tumor and subsequently developing a second solid tumor. However, the proportion of second cancers that might be related to radiotherapy has not been investigated before, they said.
Dr. Berrington de Gonzalez and her colleagues used data from the U.S. SEER (Surveillance, Epidemiology, and End Results) cancer registry to perform "a comprehensive and systematic analysis of all first solid cancer sites in adults that are routinely treated with radiotherapy." They included 647,672 patients who were 5-year cancer survivors and were aged 20 years and older when they were diagnosed with a first primary invasive solid cancer in 1973-2002. The participants were followed for 5-34 years (mean follow-up, 12 years) for the development of a second solid cancer.
The study included 15 possible sites of solid cancer that usually receive radiotherapy as the first course of treatment: oral/pharynx, salivary gland, rectum, anus, larynx, lung, soft tissue, female breast, cervix, endometrial, prostate, testes, eye/orbit, brain/central nervous system (CNS), and thyroid. "We excluded hematological cancers from both the first and second cancer sites because of potential confounding by chemotherapy," the investigators said.
A total of 60,271 study subjects (9%) developed a second solid cancer. "There were an estimated 3,266 excess second solid cancers that could be related to radiotherapy ... in our analysis; more than half of these were in breast and prostate cancer survivors," they said (Lancet 2011 March 30 [doi:10.1016/S1470-2045(11)70061-4]).
"We estimate that 8% of the 42,294 second solid cancers diagnosed in patients that survived longer than 1 year could be related to radiotherapy. ... For every 1,000 patients treated with radiotherapy, we estimated [three excess] cancers by 10 years after first cancer diagnosis, and [five excess] cancers by 15 years," they added.
Attributable risk was highest for seminomas (24%) and cancers of the cervix (17%), nonlimb soft tissue (15%), salivary gland (12%), and anus and prostate (10% each); it was lowest for cancers of the eye or orbit (4%), and oral/pharynx, larynx, and female breast (5% each). Attributable risk was intermediate for cancers of the lung (6%), rectum and thyroid (7% each), and endometrium and brain/CNS (9%).
In general, attributable risks followed expected patterns: They were higher for sites that are typically exposed to higher doses of radiation, for patients who were younger when they were exposed to the radiation, and for patients who had survived the longest time since diagnosis of the first cancer.
The strengths of this study were its large sample population and long follow-up. Weaknesses included the lack of data on smoking status and on the use of chemotherapy or hormone therapy, which could confound the results.
In addition, "since all the patients were treated before 2003, the effect of the widespread introduction of intensity-modulated radiotherapy (IMRT) could not be assessed. There is concern that IMRT might actually increase second-cancer risks because of the greater volume of tissue that receives low-level radiation exposure, and it will be important to study this directly in the future," Dr. Berrington de Gonzalez and her associates said.
Overall, the study results demonstrate that the risks of developing a second cancer after receiving radiotherapy in adulthood "are relatively small, especially when compared with the treatment benefits," they added.
This study was funded by the National Cancer Institute. No financial conflicts of interest were reported.