Study: CT screening may up cancer risk for those with genetic mutation

Individuals with the lung cancer-susceptibility gene Ki-ras may be more susceptible to radiation-induced cancers than individuals who don’t express the mutation, according to animal model research published in the December issue of Radiation Research. In the wake of the National Lung Screening Trial (NLST), which linked annual CT screening with a 20 percent mortality reduction, researchers from Wake Forest Baptist Medical Center in Winston-Salem, N.C., sought to determine the carcinogenic risk of annual CT screening exams.

“The NLST is an important and significant study, however, that trial did not include a risk-benefit analysis with respect to potentially promoting cancer due to the corresponding CT radiation exposure. Therefore, more research is needed to assess the effects of clinically relevant low dose CT exposure,” Michael T. Munley, PhD, associate professor of radiation oncology, and colleagues, told Health Imaging.

The researchers noted that current and former heavy smokers ages 55 to 74 are likely to have initiated cells progressing to or ready to progress to premalignant or malignant lesions in their lungs.

Radiation exposure during screening CT studies could initiate normal cells to become tumor cells or promote the growth of initiated cells into tumors, according to the researchers. “This conundrum highlights the need to better define the carcinogenic risk associated with annual CT screening of current and former smokers,” wrote Munley.

Mark S. Miller, PhD, professor of cancer biology, at Wake Forest Baptist, offered a hypothetical scenario to illustrate the point. “Suppose we were to screen 100,000 heavy smokers or ex-smokers annually by CT. According to statistics, approximately 20,000 of these individuals will get cancer, and only 3,000 patients will survive five years. If we screen by CT and find lesions earlier, the 20 percent decrease in mortality predicted by the NLST would suggest that an additional 750 patients would survive beyond five years. The key question, which has yet to be answered, is how many new cancers might be caused by the annual CT screening.

“If annual screening causes a 0.1 percent increase in lung cancer, then out of 100,000 patients screened, we might cause an additional 100 cancers. Is it okay to increase survival of 750 people if the cost is 100 procedure-related cancers? What if the CT procedure causes a 0.5 percent [an additional 500 cancers] or 1 percent [1,000 new cancers] increase?“

The researchers designed an animal model that controlled for variables and uncertainties and examined how CT scans affected mice bred with the lung cancer-susceptibility mutation Ki-ras, which is implicated in about 30 percent of adenocarcinomas, the most common type of lung cancer.

Mice that expressed the mutation were exposed to multiple whole-body CT doses that approximated the NLST screening protocol. After exposure, mice with the Ki-ras gene had 43 percent more tumors than unirradiated mice, and females were more susceptible than males.

“We believe we are the first to use an animal model in an actual clinical CT scanner to directly look at the risk of producing tumors after a diagnostic procedure,” Munley and Miller said in a statement. “What we found is that there may be an increased risk of tumor formation from CT scans in certain individuals with cancer susceptibility.”

The irradiated mice that did not express the mutant Ki-ras gene had no increase in tumors.

The findings suggested that the widely used linear no threshold model may be an inappropriate means of estimating cancer risk from CT exposure for current and former smokers. “These results suggest that any increased carcinogenic risk after exposure to fractionated low-dose CT radiation may be restricted to only those individuals expressing cancer susceptibility genes in their tissues at the time of exposure,” the researchers wrote, adding that individuals who do not have the cancer susceptibility gene may face little to no risk with low-dose CT radiation.

Limitations of the study include the focus on only one gene associated with lung cancer and the use of CT imaging to monitor tumors in the mice.

Munley et al recommended a cautious approach and said, “Lung cancer screening in current and former heavy smokers is important. CT is the imaging modality of choice, however, if an individual is known to have an expressing mutant Ki-ras gene (or cancer susceptibility gene) imaging using MRI should potentially begin to be considered to avoid any possible additional cancer risk attributable to the CT scan. … The discussion over which imaging modality to choose should occur between the individual and their physician.”

In the interim, the researchers are attempting to determine if there is a low-threshold dose for CT that is both safe in terms of future cancer risk and produces a diagnostic image that is of acceptable quality to be clinically useful.