Small proportion of excess second solid cancers attributed to radiotherapy

de Gonzalez AB. Lancet Oncol. 2011;doi:10.1016/S1470-2045(11)70061-4.

Issue: May 10, 2011

A review of data collected in SEER databases showed that radiotherapy was associated with relatively few second solid cancers, responsible for only five cancers in 1,000 patients 15 years after treatment.

Researchers looked at nine SEER registries to evaluate 15 cancer sites 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 central nervous system, and thyroid). More than 20% of patients who underwent radiotherapy as part of their first treatment course were diagnosed with cancers at those sites. Additionally, researchers had data on more than 200 second cancers at those sites, which stabilized risk estimation.

The study included 647,672 patients who were treated from 1973 to 2002 and survived at least 5 years after radiation exposure. Patients were followed for a median of 12 years.

During the follow-up period, 9% of 5-year survivors developed a second solid cancer. The RR for developing a second solid cancer associated with radiotherapy was more than 1, and the increased risk for most first cancer sites was each of the first cancer sites. However, adjustment for stage at diagnosis, age at diagnosis and year of diagnosis of the first cancer generally reduced the RRs.

The adjusted RR for radiotherapy varied from 1.08 (95% CI, 0.79-1.46) for cancers of the eye and orbit to 1.43 (95% CI, 1.13-1.84) for testicular seminoma. Restricting the cohort to patients treated with surgery did not change the RRs by more than 10%, except for cancers of the eye and orbit, which were based on very small numbers.

“When we assessed the RRs associated with radiotherapy treatment for the group of second cancers that were related to smoking we found that these risks were often higher than the risks for second cancers not related to smoking, suggesting possible confounding by smoking,” the researchers said.

The RR for the high-dose second cancer sites varied from 1.03 (95% CI, 0.71-1.47) for thyroid cancer to 1.78 (95% CI, 1.42-2.22) cervical cancer. There was a highly significant trend across dose groups for cancers of the female breast, endometrium and prostate.

We have known for 100 years that radiation can cause cancer, and that there is a risk that patients treated with radiation therapy could develop cancer later on. The risk is greater for children, and it’s greater with higher doses of radiation. What we were not sure about was whether the risk for second cancers associated with radiation therapy was large or small. These results suggest that it is quite a small problem overall. I was very reassured. The problem was much smaller than some had feared. When one considers the number of cancers treated and cured relative to the number of cancers induced, the risk of radiotherapy remains incredibly low compared with the benefits gained. Additionally, this data comes from patients treated from 1973 to 2002. Radiation technique has become much more focused over the past decade, so I suspect these findings will turn out to be an overestimate when looking at patients treated with contemporary radiation.

Anthony L. Zietman, MD
Professor of Radiation Oncology, Harvard Medical School

Disclosure: Dr. Zietman reported no relevant financial disclosures.

Follow HemOncToday.com on Twitter.