Lancet: Radiotherapy-induced cancers pale compared to benefits

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Radiotherapy treatment of first cancers results in an estimated five radiation-induced cancers per 1,000 patients, amounting to a small proportion of overall second cancers and a minor risk compared with the protections afforded by radiotherapy, argued the authors of a study published online March 30 in The Lancet.

Cancer survivors are known to have a significantly increased risk of acquiring additional cancers than cancer-free individuals—estimated at 14 percent higher—such that subsequent cancers account for 18 percent of all diagnoses in the U.S. The benefits of radiotherapy are almost universally believed to outweigh the risks, although reliable estimates of the risk of radiotherapy-induced cancer are lacking.

Preliminary studies have estimated that between roughly 5 and 6 percent of second cancers result from radiotherapy itself, with the rate varying according to first cancer sites, time since diagnosis and patient age. Based on a sample of 647,672 cancer survivors, the authors attempted to estimate the risk of cancer posed by radiation therapy, while looking at variables including cancer site, therapy dose and age.

The authors pulled information from the U.S. Surveillance, Epidemiology and End Results (SEER) cancer registries, including patients with initial cancers in any of 15 different sites who survived at least five years (the minimum lapse through which risk from radiation is believed to remain latent). Patients were followed for a mean of 12 years.

A total of 60,271 of the 647,672 five-year survivors were diagnosed with second malignancies during follow-up—within which every first-cancer site was associated with a higher risk of acquiring a subsequent cancer if patients received radiation therapy compared with survivors who did not.

“Our results suggest that about 8 percent of second solid cancers might be related to radiotherapy treatment for the first cancer,” explained Amy Berrington de Gonzalez, PhD, a researcher with the radiation epidemiology branch of the National Cancer Institute in Bethesda, Md., and colleagues. The findings suggest radiotherapy induced five excess cancers per 1,000 patients within 15 years of treatment, according to the researchers.

The relative risks for acquiring one of the 3,266 estimated radiation-induced cancers increased significantly with each passing year from the first cancer’s diagnosis. Meanwhile, older patients had lower relative risks of acquiring second cancers.

First cancers of the testes, cervix, non-limb soft tissue and salivary gland had the highest risks attributable to radiation, amounting to between 12 and 24 percent of all second cancers for those initial sites. First cancer sites demonstrating the lowest relative risks included cancers of the eye and orbit, oral/pharynx, larynx and female breasts, with the attributable risks not exceeding 5 percent.

Berrington de Gonzalez and colleagues noted that because their study included an especially long follow-up, the effects of newer radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT), could not be assessed. The authors also considered that smoking might have been a confounding variable in the radiotherapy risk attributions.

Among the nine cancer sites for which the authors performed a response analysis based on administered dose, six showed higher relative risks of radiation-induced cancer for high therapeutic doses (above 5 Gy). For cancer of the female breast, endometrium and prostate these trends were highly significant.

In the final analysis, though, Berrington de Gonzalez and co-authors argued that, “Even if current practice substantially changed radiation doses to some organs, the general message remains unchanged: the second cancer risks from radiotherapy in adulthood are relatively small, especially when compared with the treatment benefits.”