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Vol. LXV, No. 4
February 15, 2013
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Becoming Major Cause of Cancer
NCI’s Berrington Outlines Risks of Medical Radiation

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NCI’s Dr. Amy Berrington de Gonzalez says medical radiation is becoming a major cause of cancer

NCI’s Dr. Amy Berrington de Gonzalez says medical radiation is becoming a major cause of cancer

Among the world’s developed nations, the United States is notably aggressive in the pursuit of technologies employing radiation for both diagnostic and therapeutic procedures. And while there’s no doubt that CT (computed tomography) scans, X-rays and cardiac stress tests (which use radioactive tracers) represent medical progress and save lives, the frequency with which we use them may be increasing cancer rates, to the point that physician-directed radiation is becoming one of the top 10 causes of the disease.

So reported Dr. Amy Berrington de Gonzalez, senior investigator in NCI’s Radiation Epidemiology Branch, at a Jan. 11 talk in Wilson Hall titled “Medical Radiation and Cancer Risk: Assessing the Price of Progress.”

In the last 15 years of her career, Berrington, a native of England who earned her Ph.D in epidemiology at Oxford, has been able to demonstrate that medical radiation is emerging globally as a major cause of cancer. At NIH for the past half decade, she has participated in large-scale studies proving that there is a downside to our technological hunger for more and better radiation-dependent imaging modalities.

Continued...

The use of medical radiation “is undoubtedly one of the greatest advances in medicine of the 20th century,” she said. “There’s no doubt that medical radiation saves lives and detects disease early.” But it was evident early on that radiation could itself induce cancer.

In 1902, it became clear that radiation was causing skin cancers in the hands of radiologists, Berrington noted, and by 1931 it was linked to cases of leukemia. In 1944, U.S. radiologists confirmed a link to cancer from medical radiation, and just over a decade later, epidemiologists in the U.K. initiated a cohort study to further define the risk.

Famed Oxford epidemiologists Richard Doll (who became a mentor to Berrington) and Richard Peto estimated, in a 1981 paper, that medical radiation could be responsible for around 0.5 percent of cancer deaths. Berrington learned from Doll that this was a “back-of-the-envelope” calculation; he encouraged her to re-explore the topic, despite a skeptical reception from some of her other colleagues.

It turns out that most of what we know about ionizing radiation and its link to cancer comes from long-term follow-up studies of atomic bomb survivors in Japan, Berrington explained. “We learned that risk is linear with dose, that risk remains elevated through life and that radiation can cause most [types of] cancers. The risk is also higher the younger you were at age of exposure.”

The risks of medical radiation have been proven in a variety of studies in recent decades: cumulative doses of fluoroscopy (chest X-ray) for detection of tuberculosis have been linked to increases in breast cancer; X-rays to detect scoliosis (curvature of the spine) are associated with elevation in breast cancer; and scalp irradiation as a therapy for tinea capitis (fungal infection of the scalp) is linked to cancers of the thyroid and brain.

Berrington (l) chats with NCI’s Dr. Christine Berg and NIH deputy director for intramural research Dr. Michael Gottesman before her talk in Wilson Hall.

Berrington (l) chats with NCI’s Dr. Christine Berg and NIH deputy director for intramural research Dr. Michael Gottesman before her talk in Wilson Hall.

Photos: Ernie Branson

Berrington did her Ph.D. thesis on “risk projection,” or the proportion of cancer attributable to diagnostic radiation exposure. She estimates that, in countries such as the U.K., where diagnostic exposure is relatively low, only about half a percent of cancers appear attributable to CT scans (CT scans use 10 times the radiation of conventional X-rays). But in countries that are quick to use such testing, such as the U.S., Germany and especially Japan, the percentage rises, respectively, to 1, 1.5 and about 3.5 percent.

In 1980, in the U.S., only about 3 million CT scans were performed, Berrington reported. By 2007, that number rose to 70 million scans.

“For 25 years, we didn’t really know what was happening [with such scans as a potential cause of cancer],” she said.

Since 2000, there has been about a 10 percent annual rise in the use of multidetector CT scans. “We’re not just talking about an increase in volume,” she explained, “but also in dose levels.”

Berrington estimates there will be 29,000 eventual cases of cancer from the CT scans performed in 2007 alone.

While CT scans saw the greatest increase in diagnostic deployment, the number of nuclear medicine cardiac stress tests jumped 9-fold between 1980 and 2008, said Berrington. “Those tests involve 2 to 5 times higher radiation than CT.”

She estimates 7,500 future cancers from a single year’s worth of cardiac stress tests.
A particular worry for Berrington and her colleagues is pediatric CT scans. “And that’s not so much due to volume as to concerns about higher cancer risks and higher radiation doses in this population,” she said.

In a U.K.-NCI CT scan study of more than 200,000 youngsters from more than 100 hospitals, conducted from 1985 to 2002, a 10-year follow-up found 74 leukemias and 135 brain tumors. “These are the most highly radio-sensitive and common childhood cancers,” said Berrington. “There is a clear dose-response relationship. There was a tripling in the risk of leukemias, and almost the same [rise] in the brain. These are highly statistically significant results. And they are consistent with the A-bomb data for leukemias and brain tumors.”

Berrington calculates the absolute (versus relative) risk of cancer due to medical radiation as 1 excess case per 10,000 CT scans.

“This is the first direct evidence of possible cancer risk after pediatric CT scans,” she said. “It is an established carcinogen, there is a dose-response relationship, although the brain cancer risk may be overestimated.”

Berrington takes audience questions on Jan. 11.
Berrington takes audience questions on Jan. 11.

Replication studies are already under way in Canada, Australia and Israel, she said. This spring, NCI will host a collaborators’ meeting from this international CT scan pooling project that involves more than 1 million children.

There are already a variety of risk-mitigation programs in effect, with such sponsors as the Institute of Medicine, the American College of Radiology, the World Health Organization and the FDA, Berrington noted, but varying “levels of overuse” around the world concern her. “If we don’t change practice and reduce use and dose levels, risks will continue to rise,” she warned.

Absent strong criteria for appropriateness, reliance on such alternatives as MRI and ultrasound and especially the avoidance of repeat procedures, Berrington fears that the percentage of cancers due to medical radiation in the U.S. will rise from 1 percent to around 3 percent, “and could become one of the top 5 causes of cancer.”

Turning briefly to therapeutic, rather than diagnostic, uses of radiation, she noted that there are some 12 million cancer survivors in the U.S. This population has a 14 percent higher risk of subsequent malignancy than the general population. Berrington says such elevation in risk is “most likely a combination of factors responsible for the first cancer, but also due to treatment for the first cancer.”

Examining the proportion of second cancers due to radiotherapy in a population of adults with solid tumors, Berrington found that about 8 percent of such cancers seemed tied to therapy. She calculated the absolute risk as 5 excess cancers per 1,000 patients by 15 years post-therapy.

Berrington hopes that advances in epidemiological modeling techniques—as a way to track the effects of medical radiation—keep pace with new modalities that use even more powerful radiation, including IMRT (intensely modulated radiotherapy) and proton therapy (there were 9 machines introduced in the U.S. in the period 2004-2012; 2013 alone will see 9 more), which can result in neutron exposure, which may involve “possibly a 10 times higher risk” of causing cancer.

“Particularly in the United States, the technology can change rapidly, with corresponding increases in use,” Berrington said. She emphasized that “if the test [involving medical radiation] is clinically needed, the risk is justified…We need to assess the balance between risks and benefits.”


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