Two recently published articles by D.J. Brenner 1,2 regarding the risks associated with radiation-induced cancers that may be produced by CT screening have caused much concern. In view of the ongoing controversy surrounding these examinations and concerns about the risk/benefit ratio associated with them, it is important to have a clear understanding of how the author reached his conclusions and to assess their tenability. For illustrative purposes, I will focus on lung cancer screening although a similar analysis could also be performed in regard to whole body screening since the approach taken to assess the risk was similar.
The approach used by Brenner for estimating the mortality due to radiation-induced lung cancer can be summarized as follows. The dose of a single screening examination is estimated and then multiplied by the number of scans a subject would be expected to receive over a lifetime to arrive at the total lifetime dose. Using data extrapolated from atomic bomb studies to estimate the number of lung cancers induced by a specific dose, this estimate is then applied equally to the lifetime dose the subject would receive from CT to estimate the number of cancers induced for the chosen population. The 95% confidence intervals surrounding this estimate are given, and using the upper limit of these intervals, a final estimate of 5.5% increased incidence of lung cancers is reached. This leads the author to conclude that for CT screening for lung cancer to be useful, “A mortality benefit of considerably more than 5% may be necessary to outweigh the potential radiation risks.” 1
In the following section, I will explicitly list some of the assumptions that Brenner makes and comment on their general acceptability.
Assumption No. 1. The estimated dose from a single low dose CT is 5.2 mGy.
Comment: This is approximately twice the dose that is currently estimated for lung cancer screening. 3
Assumption No 2. The number of scans to be performed would be 25, starting at age 50 and ending at age 75.
Comment: I do not know of anybody recommending continuous low dose CT screening for lung cancer over a 25-year duration. One of the main concerns in ongoing research is to determine the optimal frequency with which these studies should be performed.
Assumption No. 3. Risk estimates based on the sum of multiple low doses obtained over extended periods of time are equivalent to receiving the entire dose at a single time.
Comment: This is not the case for higher doses as would occur in radiation therapy where fractionation of the dose lowers the risk of cancer induction. There is no direct evidence that it is true for low dose, with some evidence suggesting the opposite, and this remains controversial. 4,5
Assumption No. 4. Dose estimates from atomic bomb survivors can be extrapolated to medical imaging.
Comment: This is controversial, as along with other biases that are thought to be present in recording data from this group, there is concern that the type of radiation was quite different in the atomic bomb survivors, and may have had a greater propensity to induce cancer.4 In regard to any lung cancer induction, especially at low dose, some have interpreted the atomic bomb data as being inconclusive. 5
Assumption No. 5. Propensity for cancer development in the Japanese population can be extrapolated to the US population.
Comment: Brenner acknowledges that this estimate has “great uncertainty.” 1
Assumption No 6. The rate of cancer induction from low dose radiation medical radiation, such as CT, can be estimated using a linear non-threshold model (LNT).
Comment: There is no direct evidence to support this. This topic is controversial, and this model may overestimate the rate. The International Commission on Radiological Protection (ICRP) has emphasized the putative nature of this hypothesis. 6
Assumption No. 7. Use of non-smoking dependent registries, as were used by Brenner in his estimates, can be used to estimate lifetime lung cancer risk.
Comment: While these estimates are frequently used, Brenner acknowledges errors of up to 10% associated with them. 1
Assumption No. 8. Radiosensitivity in the lung increases with age.
Comment: This is controversial, and there is evidence to suggest that the lung is less sensitive to low dose radiation than other organs, with no associated excess risk. 5
Assumption No. 9. The induced lung cancer rate can be equated with mortality
Comment: Induced lung cancer, particularly in the screening environment where there would be a high probability of finding it early, may be quite treatable.
Assumption No. 10. It is appropriate to estimate the excess number of lung cancers induced, develop confidence intervals around this estimate, and then use the upper bound (approximately three times higher) of this estimate as the final result.
Comment: This approach can be misleading. The estimate itself should be applied, as the wide confidence intervals merely reflect the uncertainty of the data used to form the estimate.
The assumptions made by Brenner in each of these instances have a tendency to overestimate the risk of dying of lung cancer. As an example, by simply using the current dose estimates for low dose lung screening, which are about 50% of those used by Brenner, and using Brenner’s own estimate of excess cancer risk, which is 33% of its upper bound, without changing any of Brenner’s other assumptions, the excess cancer risk would be cut to less than 1%. In my view, given all of the other assumptions made by Brenner, which favor excess deaths, it is likely that the risk would be even lower. As background dose estimates in the United States are 3 mSv, with up to 10 mSv allowable for radiation workers per year, 7 it is unlikely that estimates for excess cancer risk induced by low dose CT could be separated from statistical noise, especially since 23% of deaths in the United States are caused by cancer. 8
Extrapolations such as those performed by Brenner, and then applied to populations to estimate cancer risks, are generally fraught with controversy. 4 While it may be useful to perform these types of estimates so as to encourage the ALARA principle (As Low As Reasonably Achievable), this is quite different than applying them to populations and estimating mortality rates. As Brenner himself has noted, “It seems unlikely that we will be able to directly estimate risks at significantly lower doses than these [50 mSv] because of the practical limits of epidemiology. Of course, the fact that risks cannot be directly estimated at doses below, say 5 mSv, does not imply any conclusion as to whether risks actually exist at these lower doses.” 9
This type of concern for risks associated with radiation was raised many years ago in regard to mammography, and resulted in a setback of several years before a more reasonable approach was taken, and mammographic screening was accepted. 10 While there are many areas of concern regarding the use of screening CT, the approach taken in these articles, which exaggerates the risks, is ultimately not helpful in determining the genuine risks and benefits associated with them.
David Yankelevitz, MD, is professor of radiology, Weill Medical College of Cornell University, New York City, and co-principal investigator of the International Early Lung Cancer Action Program.
- Brenner DJ. Radiation risks potentially associated with low-dose CT screening of adult smokers for lung cancer. Radiology. 2004;231:440-5.
- Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CT screening. Radiology. 2004;232:735-8.
- McNitt-Gray MF. Radiation issues in computed tomography screening. Radiol Clin North Am. 2004;42:711-23.
- Kellerer AM. Risk estimates for radiation-induced cancer — the epidemiological evidence. Radiat Environ Biophys. 2000;39:17-24.
- Rossi HH, Zaider M. Radiogenic lung cancer: the effects of low doses of low linear energy transfer (LET) radiation. Radiat Environ Biophys. 1997;36:85-8.
- The 1990 Recommendations of the International Commission on Radiological Protection. Annals of the ICRP, Vol 21, No. 1-3. Oxford, England: Pergamon Press; 1991. IRCP Publication 60.
- Limitation of Exposure to Ionizing Radiation. Bethesda, Md: National Council on Radiation Protection and Measurements (NCRP); 1993. Report 116.
- Landis SH, Murray T, Bolden S, Wingo PA. Cancer Statistics, 1999. CA Cancer J Clin. 1999;49:8-31.
- Brenner DJ, Doll R, Goodhead DT, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci U S A. 2003;100:13761-6.
- Bailar JC 3rd. Mammography: a contrary view. Ann Intern Med. 1976;84:77-84.