麻豆传媒

A single low-dose chest CT (LDCT) scan did not cause statistically significant human chromosomal DNA damage, but notable increases in two markers of DNA damage were observed immediately following a single standard-dose chest CT scan (SDCT), Japanese researchers reported.

Results from a prospective study measuring biologic markers of DNA damage in peripheral blood samples taken before and after a single chest CT showed that in 107 patients who underwent LDCT, there was no significant increase in the number of DNA double-strand breaks (0.15 vs 0.17 per cell, respectively, P=0.45) or in the number of chromosome aberrations (CAs; 6.7 vs 7.2 per 1,000 metaphases, P=0.69). The median effective dose was 1.5 mSv/3.5-mGy blood dose, according to Satoshi Tashiro, MD, PhD, of Hiroshima University in Japan, and colleagues.

However, in 102 patients who underwent SDCT at a median effective dose of 5 mSv/13.3-mGy blood dose, there was a significant increase in the number of DNA double-strand breaks before versus after CT (0.11 vs 0.16 per cell, respectively, P<0.001), and in unstable CAs (7.6 vs 9.7 per 1,000 metaphases, P=0.003), they wrote in Radiology.

"Although to our knowledge no direct association between CT-induced adverse biologic changes and cancer risk has been established, the indicates that radiation exposure must be minimized," the authors stated. They used the same low dose recommended by the National Comprehensive Cancer Network LDCT lung cancer screening , so "the goal of dose reduction of chest CT can be set at around 1.5 mSv," they added.

"Even using these sensitive analyses, we could not detect the biological effects of low-dose CT scans," Tashiro said in a statement. "This suggests that application of low-dose CT for lung cancer screening is justified from a biological point of view."

The number of LDCT-induced double-strand breaks and CAs, which were approximately 30% lower after LDCT than SDCT (P<0.001), was not significantly correlated with the dose-length product, the effective dose, or the calculated blood dose, the researchers said. SDCT is an effective diagnostic tool that is appropriate when the benefits outweigh any potential risk, they added.

In an accompanying editorial, David J. Brenner, PhD, DSc, of the Center for Radiological Research at Columbia University Irving Medical Center in New York City, noted that this biologic approach to estimating possible cancer risks associated with the LDCT scans is not new. But, "it represents a substantial advance because of the scale of the study, its use of two doses, and two DNA damage end points," he added.

Nevertheless, the "admirably large" study was not large enough to provide good evidence either way regarding zero risk in the LDCT chest group, Brenner said, pointing out that 47% of patients in the LDCT group still showed increased DNA damage compared with 64% in the SDCT group. "So, even with a substantially reduced dose, the number of affected individuals changed comparatively little," he stated.

Epidemiologic of cancer risk with low-dose ionizing radiation have demonstrated the same pattern of decreasing risk with decreasing dose, Brenner noted. To achieve statistical significance, "exponentially more participants are required," he pointed out, adding that since the study used almost the same number of participants in each CT dose group "loss of statistical significance at the lower dose is not surprising."

Ultimately, the question of whether radiation risk is zero or merely minuscule "is neither here nor there for a patient who needs to undergo CT," Brenner said. No causal link between DNA double-strand breaks and cancer risk has been established by any of the research to date, and most CT examinations are of "enormous benefit," he noted. However, the issue of identifying the small subset of individuals in the general population with a genetic predisposition to radiation-associated at low radiation doses remains a challenge, Brenner said.

James A. Brink, MD, radiologist-in-chief at Massachusetts General Hospital in Boston, agreed that the current study makes an important contribution to the literature by increasing understanding about the impact of radiation on the human body.

"We never get to a clinically relevant conclusion without taking these steps," said Brink, who was not involved in the study.

Because these biologic changes have not been directly correlated with an increased risk of lung cancer, "we should be cautious about extrapolating these findings into clinical care," Brink told 麻豆传媒. "These are not clinical endpoints."

For the study, the researchers prospectively enrolled 105 women and 104 men referred to a respiratory surgery department for chest CT studies between March 2016 and June 2018. The two groups were similar in sex distribution, age, and body size metrics. The mean age was 67.0. Those who had undergone radiography examination in the previous 3 days, or who had been treated with chemotherapy or radiation therapy, were excluded.

The researchers measured the number of gamma-H2AX foci, a marker of DNA double-strand breaks. Prior to statistical analysis, they also measured the number of unstable CAs in lymphocytes. These biologic markers reflect both the damage from radiation exposure and the accuracy of DNA repair.

After observing a slight difference in the number of CAs before and after CT, the investigators conducted a secondary investigation to rule out the possibility that this finding reflected differing radiation sensitivities among the study participants. In 63 participants who agreed to undergo both LDCT and SDCT, the results confirmed that the number of DNA changes was greater after SDCT versus LDCT.

"Compared with previous reports that used single biologic analysis, we believe that our two independent biologic analyses yielded highly reliable findings," Tashiro and colleagues said. "We are interested in the biological effects of various types of radiological diagnosis, including PET/CT, to establish a better system for the management of medical radiation exposure."

Study limitations included the lack of random assignment of the CT protocols, and the fact that DNA damage was assessed in peripheral blood lymphocytes only. DNA damage may be different in solid organ tissues such as the lung, the researchers said.

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