The risk of increased cancer incidence associated with low-dose ionising radiation is an extremely controversial topic [3
]. This reflects both the limited available data, which predominantly derive from the survivors of the atomic bombs in Japan, and the scepticism on the “linear no threshold” model proposed to describe such effects. Further uncertainties derive from the adoption of the effective dose as an indicator of the cancer risk specifically for the individual subject [19
] and, in the case of lung cancer screening with LDCT, from the suggestion of a possible multiplicative effect of smoking and radiation exposure in increasing the incidence of lung cancer [21
However, little is known about the actual dose exposure associated with lung cancer screening using LDCT, which is the basis for calculation of the risk of radiation-induced cancer.
In a pioneer study published in 1996, Nishizawa et al [2
] used phantom measurements to determine organ or tissue doses from chest examinations performed using a prototype CT system developed for lung cancer screening, with a single row of detectors' spiral scanning capability. The effective dose per LDCT examination was 3.6 mSv and the dose to the lung was 5.2±0.9 mGy. These doses were one-half to one-third lower than the doses using standard CT systems and protocols at that time and the authors concluded that “the risk-benefit analysis showed that the benefit will exceed the risk for Japanese over 40 years for men and over 45 years for women” [2
]. However, using the same dose data but a different risk–benefit model, Brenner [3
] concluded that “given the estimated upper limit of a 5.5% increase in lung cancer risk attributable to annual CT-related radiation exposure, a mortality benefit of considerably more than 5% may be necessary to outweigh the potential radiation risks”.
10 years later we reported the effective dose delivered in a 3 year pilot study involving 60 smokers performed using a single-detector or a 4-row detector spiral CT scanner and found that the mean individual effective doses were 5.9 mSv per 3 years and 1.9 mSv per year with the single-detector scanner and 1.4 mSv per 3 years and 0.4 mSv per year with the multidetector scanner [4
]. The lung dose for a single LDCT examination ranged between 3.2 mGy with the single-detector CT scanner and 0.8 mGy with the multidetector scanner. In the same study we included a risk–benefit analysis for the subjects receiving screening in the ITALUNG trial assuming not only the dose associated with LDCT examinations but also that related to further investigations, which included follow-up LDCT examinations, contrast-enhanced CT, chest FDG-PET and CT-guided FNAB, and concluded that the ratio was favourable for current smokers if screening reduces lung cancer mortality by at least 20% [4
In the present report we computed the collective effective dose actually delivered to the 1406 subjects who, after randomisation, underwent the ITALUNG screening protocol. In particular, after software measurements of the effective dose associated with annual LDCT examinations on the eight spiral scanners, we took into account the effective dose associated with chest PET after intravenous administration of a standard quantity of FDG [13
] and considered effective dose values associated with CT-guided FNAB we previously measured [4
] using the scanners on which all such procedures were carried out in the trial.
As expected, the effective and organ doses for the single LDCT examination measured in all eight of the spiral scanners of the study were considerably lower than those measured by Nishizawa et al [2
], reflecting technological development. In particular, the average effective dose was 1.2 mSv for sV acquisitions and 1.4 mSv for lV acquisitions, while the corresponding average dose to the lung was 3.4 mGy for sV and 3.6 mGy for lV acquisitions.
Overall the mean collective effective dose actually delivered to the subjects who underwent LDCT in the ITALUNG trial ranged between 6.22 and 6.85 Sv per 1000 subjects depending on the length of the spiral acquisition volume of the LDCT. The corresponding mean effective dose to a single subject enrolled in the study over 4 years ranged between 6.2 and 6.8 mSv according to the cranial–caudal length of the LDCT volume. This individual effective dose falls in the very low-risk <10 mSv exposure category [19
] and represents about one-third of the dose owing to natural background and diagnostic radiological procedures received by Italian subjects not undergoing screening in 4 years—that is, 18 mSv (4.5 mSv per year ×4) [22
In only two subjects who underwent annual and follow-up LDCT mainly on a single-detector scanner and one chest FDG-PET each, the individual effective dose was approximately 20 mSv in 4 years.
The above mean collective effective dose is slightly lower than the one we previously estimated for a screening programme exclusively using a single-detector scanner (7.12 Sv), but higher than the one we estimated exclusively using a four-detector scanner (3.35 Sv) [4
The following reasons presumably account for the discrepancy. (1) In the former analysis we hypothesised two scenarios in which screening was performed uniformly using either a single-detector or a four-detector scanner and not a combination of the two plus other multidetector scanners, as was actually the case in the ITALUNG trial. However, the proportion of LDCT examinations performed on a single-detector scanner, implying higher dose exposure than multidetector scanners [4
], was small (13.9%). (2) In the trial the rate of follow-up LDCT examinations performed after baseline and annual repeat screening rounds (30% and 15%, respectively) were higher than the 10% predicted. (3) The number of further investigations involving radiation exposure, in particular chest FDG-PET, was higher than previously estimated. In fact we predicted 1.0% of further investigations at baseline and 0.5% at each annual repeat for an overall rate of 2.5% [4
], but in the ITALUNG trial we carried out chest FDG-PET scans in 6.7% and CT-guided FNAB procedures in 2.5 % of subjects.
Notably, in the present survey the effective dose related to further investigations for suspicious nodules including follow-up LDCT, chest FDG-PET and CT-guided FNAB accounted for 22% of the collective effective dose.
The combination of the collective effective dose with the nominal risk coefficients for stochastic effects after exposure to low-dose radiation indicates a substantially low risk. In particular, according to NRPB estimates [14
], the numbers of potential fatal cancers associated with the collective effective dose in the ITALUNG trial ranged between 0.09 and 0.37 per 1000 subjects, while they ranged between 0.11 and 0.24 per 1000 subjects in the prior projection [4
]. According to BEIR VII the number of potential radiation-induced cancers might be approximately three times higher in females than in males undergoing the ITALUNG screening programme. This reflects the fact that the risk of both lung cancer and breast cancer is considerably higher in female subjects aged 50–70 years at exposure [16
We would like to point out that the effective doses and the corresponding cancer risk we calculated in our trial are conservative and are probably overestimated for a screening programme beginning at the present time. This is because (1) multidetector CT scanners have now completely substituted single-detector spiral CT scanners in the market and their updated technology enables the delivery of a lower effective dose for each LDCT screening test compared with single-detector spiral scanners; (2) the rate of follow-up LDCT examinations we obtained at baseline and annual repeat screening rounds was on average higher than those reported in other screening programmes [23
]; (3) we considered whole lung follow-up LDCT examinations, but targeted shorter volume acquisitions can be used for control of suspicious nodules; and (4) our screening protocol included four annual LDCT examinations but other dose-sparing protocols including LDCT examinations every 2–3 years as in the Dutch–Belgian lung cancer screening trial [23
] and even a single LDCT examination as in the UK Lung Screen trial [24
] have been proposed.
Modelling of the risk–benefit ratio based on the collective effective dose requires several assumptions and calculations and is beyond the scope of the present report. However, taking account of the fact that the present data are in line with the risk of radiation-induced cancer calculated in a prior analysis [4
], and that efficacy of the screening procedure to reduce mortality from lung cancer of 20% was observed in a trial recently closed before time because of an excess of benefit in the screened subjects compared with the controls [1
], we can assume that the risk–benefit ratio is favourable for elderly current smokers and probably former smokers undergoing annual LDCT for 4 years. This positive evaluation does not necessarily apply to other target populations, including younger smokers or former smokers and non-smokers and should not be extended to other screening regimens implying longer periods of active screening.