CT imaging: does it cause to Cancer?

Concern that CT scan radiation is causing cancer has focused public scrutiny on radiologists and medical physicists—and riled up controversy among them. Can they find a solution?

Biophysicist David Brenner was in his 40s when an older colleague in New York City, a prominent pediatric radiologist, mentioned in conversation something Brenner couldn’t shake: Far too many children, the pediatrician felt, were getting computed tomography (CT) scans for ailments, such as suspected appendicitis, that used to be diagnosed easily by ultrasound or even observation. Cells in children, already more vulnerable because they divide faster than those of adults, have more time to turn cancerous after the initial damage from radiation. And a single CT scan delivers a lot of it, the equivalent of dozens to a few hundred chest x-rays. A concern about the CT boom, planted 11 years ago, began to grow.

Brenner now directs Columbia University’s Center for Radiological Research, where he focuses on exactly how radiation damage leads to cancer. He seems an unlikely candidate for a troublemaker, a passionate Beatles fan who speaks so quietly, he’s sometimes hard to hear. Yet he’s become one of the most insistent voices in an imbroglio that is roiling radiologists, medical physicists, and the general public over the rising and largely unregulated use of CT scans, and whether the technology can, in same cases, cause more harm than good.

Brenner hails from Liverpool, U.K., and his Upper West Side apartment shows it: A large black-and-white poster of a young and pensive George Harrison hangs above the sofa, and a plastic John Lennon figurine from the movie Yellow Submarine crouches next to the stereo. Settled on a couch in his living room, he explains how he moved to the center of the CT storm.

“What I thought I could contribute to this discussion was to provide some quantitative estimates of what the risks [of CT scans] actually were,” he says. These risks are surprisingly unclear, given how old and how commonly used the technology is. Brenner found that each CT scan gives a patient a very small chance of developing cancer. With hundreds of thousands of children getting CT scans every year, that small individual risk balloons into a pressing public health concern, Brenner concluded.

Many radiologists and medical physicists strongly disagree. For a single CT scan, they say, there’s no hard evidence of any raised cancer risk. Nor do they think that thousands of small, potential risks add up to a large public health problem. Furthermore, they say, the dearth of evidence makes it difficult to assess how low is low enough. But even the skeptics favor managing potential CT risks, if for no other reason than to reassure patients. That’s one of the aims behind a summit co-sponsored by the U.S. National Institute of Biomedical Imaging and Bioengineering in Bethesda, Maryland, that ends this week. Researchers there discussed standardizing protocols, estimating doses, and dose-saving technologies.

As the debate rages, the number of CT scans administered continues to soar. In 1980, 3 million scans were given in the United States. In 2006, the number was about 67 million. It shows no sign of slowing down.

How small a risk?

CT scans deliver the same type of radiation as an x-ray machine, but much more of it. As the patient moves through the scanner, x-ray beams and detectors revolve around the bed. The body’s tissues absorb radiation to varying degrees, and what gets through creates slice-by-slice, incredibly detailed images of the body part being scanned. Crafting this picture comes with potential risks. The chromosomes of a healthy cell are tangled in a “spaghetti-like formation,” Brenner explains. If radiation breaks up the chromosomes, the strands can usually repair themselves. Sometimes, though, the wrong ends meet up, scrambling the genetic information and leaving behind a premalignant cell that can bloom into cancer.

Eleven years ago, when Brenner first began considering children’s CT risks, he needed two pieces of information: the radiation delivered by a single CT scan, and the probability that a dose to a given organ would produce a fatal cancer there. For the first, he used a 1989 British survey of CT use in adults to estimate the dose children experience. For the second, Brenner turned to “the only quantitative tool we had and still have,” he says: risk calculations of radiation-induced cancer in survivors of the atomic bombings of Hiroshima and Nagasaki. The most recent were published in a report by the National Research Council in 1990 and updated in 2006.

Because data on atomic bomb survivors who had died of cancer were more robust, Brenner focused on fatal cancers. The chance of a child someday dying of cancer from one CT scan was small—on the order of one in 1000, Brenner found. But given that about 600,000 abdominal and head CT scans were performed yearly on children at the time that Brenner did his research, he and his colleagues estimated that 500 of those children might end up dying later on in life of cancer caused by the scan. Meanwhile, the total number of children who would get cancer from CT scans would be about twice that, he estimated. Brenner published his results in early 2001 in the American Journal of Roentgenology.

The paper was a sensation. “CT scans in children linked to cancer,” blared a headline in USA Today. Brenner’s use of the atomic bomb data raised “the ire of lots of people” in the medical physics and radiology communities, he says. They criticized him for extrapolating from the risks associated with extraordinarily high doses from an atomic bomb.

But Brenner says he didn’t need to extrapolate. In Hiroshima, “as you go further and further away [from the epicenter], doses get less and less, so eventually you get to a region where the doses are actually comparable to a CT scan,” he says. Brenner based his risk estimates on a cadre of about 30,000 survivors whose doses were in the range of 5 to 100 millisieverts, equivalent to one or two CT scans, he says.

Keith Strauss, a medical physicist at Children’s Hospital Boston, clearly remembers the day in 2001 when Brenner’s research was described in USA Today. The article “ruined my life for 2 weeks,” Strauss said in an interview in Philadelphia last July, at the annual meeting of the American Association of Physicists in Medicine (AAPM). His patients’ parents were suddenly full of worries and questions about their children’s scans.

By 2010, concerns about CT scans and cancer were getting plenty of attention; AAPM sessions on dose reduction were packed. Brenner had first sounded the alarm, but now others were raising concerns, too. In March 2009, the National Council on Radiation Protection and Measurements (NCRP) reported that, in 2006, CT radiation alone contributed 24% of the U.S. population’s radiation dose. In 1980, that number was 0.4%.

“The NCRP report was really the crucial one [that showed] the dramatic increase in the level of exposure,” says Amy Berrington de González, a radiation epidemiologist at the National Cancer Institute in Bethesda, who was not part of the NCRP panel. In late 2009, Berrington de González and her colleagues published a paper inArchives of Internal Medicine estimating that the approximately 70 million scans performed in the United States in 2007 would lead to about 29,000 new cancers.

There’s still a great deal of controversy, however, about how dangerous CT scans really are. Cynthia McCollough, a medical physicist at the Mayo Clinic in Rochester, Minnesota, is skeptical that there’s any evidence for the risks Brenner and Berrington de González have reported. To her, the research on doses in the CT range do not show any meaningful biological effect. Some studies, she says, suggest that low doses can even be protective against cancer, similar to how the weakened virus in a flu vaccine helps the body fight off that year’s flu. As for whether patients getting multiple scans should worry more, cells can repair themselves between scans, she says, so the damage shouldn’t be cumulative. And like others, she’s leery of looking at survivors of an atomic bomb blast.

At last November’s meeting of the Radiological Society of North America (RSNA) in Chicago, Illinois, McCollough and Brenner engaged in a public debate over whether cancer risks should be taken into account when ordering CT scans. At the end, the audience was polled and was evenly split. Brenner has his estimates, but “no one,” says James Brink, the chair of diagnostic radiology at Yale University School of Medicine, “has conclusively shown that medical radiation has caused cancer.”

Dialing down the dose

Although professionals clash over how hazardous CT scans are, they have converged to find ways to minimize a scan’s radiation dose while preserving its accuracy. Despite disagreeing with Brenner, McCollough calls herself a “dose cop.” Before buying a new machine, she doesn’t always rely on the manufacturer’s specs. Instead she has hauled her case of plastic torsos to a hospital that had the same model in order to test the doses herself.

She is also exploring how to reduce the dose from a CT scan. Accomplishing this is easier said than done, for both technological and practical reasons. Many radiologists and medical physicists expect that as CT technology improves, doses will drop. A CT angiogram, for example, was a high-dose procedure when it first came on the scene in the 1980s; the scanner would fire x-rays during the heart’s entire cycle. Then, in 2006, researchers developed a new technique that used a predictive algorithm to synch up the scan to the heartbeat. X-rays only fire during the relevant phase of the heartbeat, reducing the dose by 83%, according to one paper inRadiology. At the July AAPM meeting in Philadelphia, other dose-saving techniques were highlighted, including algorithms that can scrape the same amount of information out of lower-dose scans.

These high-tech methods work only if they’re used clinically, and CT scanners are loosely regulated. The U.S. Food and Drug Administration (FDA) is limited to overseeing the machines themselves, not how they’re applied or the training of the people who administer the scans.

Given this, most efforts at dose-reduction have been voluntary. Strauss helps direct a pediatric initiative by four radiological societies called Image Gently to remind radiologists to “child-size” the dose they give children. In November, RSNA announced the launch of a parallel campaign for adults called Image Wisely. Strauss notes that higher doses give crisper images, “so there’s no automatic incentive to cause [a radiologist] to reduce the technique to an appropriate level. It has got to be a conscious thing.”

It’s tough to tell whether the campaigns are having much effect, says Brenner. Berrington de González agrees: “I would really like to see some data to show the evidence of the effects of these campaigns.” Image Gently’s Web site allows radiologists to fill out an online form pledging to review the initiative’s guidelines and adjust their practice. The site has racked up 6506 pledges.

What those pledges translate to, practically speaking, isn’t clear. In 2008, Rebecca Smith-Bindman, a cancer epidemiologist at the University of California, San Francisco, who is also a clinical radiologist, visited four Bay Area hospitals and collected the dose that had been given to 1119 adult patients earlier that year during various types of CT exams. The median dose for abdominal and pelvic scans was 66% higher than the number usually quoted at the time. The dose from a “multiphase” version, which goes over the same area multiple times, was 400% higher. She also found that two patients could get wildly different doses, even with a scan on the same part of the body with the same machine at the same institution. Instead of following well-defined guidelines, “every doctor reinvents the wheel” in order to get a readable scan, says Smith-Bindman.

There’s growing pressure to better regulate CT machines, something FDA is considering. Sean Boyd, who heads the agency’s diagnostic devices branch, says that FDA might soon require new machines to have safety features, such as software that warns operators or even locks down the machine when the dose they’re requesting is too high. But Boyd says the agency doesn’t yet have a timeline for introducing those standards. Beginning in summer of 2012, California will require facilities to record the radiation dose of every CT study, legislation introduced after Cedars-Sinai Medical Center in Los Angeles admitted to overdosing 269 patients.

The lackluster response has Smith-Bindman and others frustrated. She wants FDA to take a more active role and cites the 1992 Mammography Quality Standards Act, which allows FDA to tightly regulate mammogram equipment, technicians, and procedures, as an example of what’s possible. “Someone has to stand up and take responsibility for this,” she says.

Then there’s the problem of excessive CT scanning, which many say is only getting worse. For someone whose symptoms necessitate a CT scan, the immediate benefits outweigh the small individual risk, says Brenner. That’s not true for those who don’t need the scan in the first place. Hedvig Hricak, the chair of radiology at Memorial Sloan-Kettering Cancer Center in New York City, sees a pattern of use in emergency departments “when the CT would be done before you even examine the patient.” There is also, Smith-Bindman says, “a financial cost motivation. It’s extremely profitable to do these tests.” Brenner adds that doctors may do the scans to help insulate themselves from malpractice suits. “There’s no doubt that people are doing CTs for defensive medicine,” he says. A 2010 study in the Journal of the American College of Radiology of 284 outpatient CT scans found that 27% “were not considered appropriate.”

Guidelines do exist: The American College of Radiology has issued what it calls “appropriateness criteria” to help doctors decide when a CT is the best course of action, but several studies have suggested that they’re not widely used. Where they are, the number of CT scans being ordered has decreased dramatically (see sidebar, p. 1003.)

Meanwhile, Brenner continues to build his case. In an October paper in the Journal of the National Cancer Institute, he suggested that cancer risks for adults, while lower than those for children, don’t decrease dramatically with age, as thought. That’s because radiation is not only an inducer, turning healthy cells into premalignant ones, but also a promoter, pushing those cells toward a cancerous state, he argues. While older bodies have cells that divide more slowly and have less time to develop cancer, they also have more premalignant cells, meaning “risks stay pretty constant through … the 30s, 40s, and 50s,” he says—right when most people begin to have health problems and go in for a CT scan.

This article is based on Lauren Schenkman‘s news focus on Science magazine:

http://www.sciencemag.org/content/331/6020/1002.full

Science 25 February 2011:
Vol. 331 no. 6020 pp. 1002-1004
DOI: 10.1126/science.331.6020.1002

 

 

 

 

 

 

 

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