Being a woman and smoking: radiation in perspective

Lung cancer screening by low-dose CT scan, or the history of a pre-announced disappointment.

In February 2020, a medical imaging  journal[1] triumphed in publishing the results of a clinical trial on lung cancer screening by low-dose chest CT, which was then widely reported in press, promoting this high technology as a systematic screening method in smoking population.

This is a scanning technique using low doses, similar to those delivered by a simple chest X-ray (in two incidences, face and profile, equivalent to 20-40 µSv, instead of 5.8 mSv for a standard chest CT), giving a slightly more degraded image, not very efficient for the analysis of interstitial pneumopathies, but sufficient for a diagnosis of small nodules.

The article in this review concluded as follows: "This study therefore seems to be in favor of organized lung cancer screening, at a time when the procedures have reached very low irradiation levels".

But what is it actually about?

Essentially two trials (there have been several studies) are supposed to provide evidence of a significant decrease in specific mortality from bronchopulmonary cancer. These are the US National Lung Screening Trial (NLST), and the NELSON trial conducted in Belgium and the Netherlands.

Already in 2014, in a guidance brief, the HAS [2] noted: ".... it is likely that the low specificity of low-dose CT screening will remain a major obstacle to the implementation of screening in clinical practice and of a screening program".
"Disadvantages and risks associated with low-dose CT screening include radiation exposures ranging from 0.61 to 1.5 mSv, a certain degree of over-diagnosis that varies between studies, and a high rate of false positive tests, usually explored with more imaging".

When we examine the study published in the NEJM [3] on the NELSON trial, the last line of Table 4 reads as follows: All-cause mortality - deaths per 1000 person-yr 13.93 (screening group) 13.76 (control group) RR 1.01 (0.92-1.11).
This clearly means that there is no impact on all-cause mortality, and this is the only data that should be of interest to the public and the media when reporting the results of such a study.

Remember that the "overall mortality" data includes everything, cancer, its treatment and its non-treatment, and reflects more adequately the "real life" data.
This information is rarely put forward, as the promoters of screening preferentially report the gain in terms of specific mortality, i.e. by the disease alone [4].

But the Academy of Medicine has retained it, and in a published report it expresses its concerns [5] [6]. The Academy notes several problems that prevent this screening from being generalized:

    - The two main trials on lung cancer screening with low-dose CT scans greatly underestimated potential harmful effects (false positives, over-diagnosis, false negatives, irradiation and over-treatment). The magnitude of  benefit and risks are unknown, and even if a 25% cure rate is achieved among subjects included in the study, the majority of patients will die early from other smoking pathologies (other cancers, heart disease, emphysema etc...) without increasing their life expectancy.

- For a screening to be effective, it is necessary to have cancers with a sufficiently long latency to be caught during a screening test (therefore as few interval cancers as possible); yet the proportion of cancers with a long latency in the lung is low.

-"These cancers are mainly due to active smoking and, marginally, to passive smoking: more than 85% of cases can be attributed to tobacco. The progressive decrease in smoking among men (from 60% of smokers in the 1960s to 33% currently) is reflected in the decrease in incidence and mortality due to these cancers", which is equivalent to saying that this cancer is simply accessible to effective primary prevention campaigns and incentives to stop the main risk factor, tobacco.

"The natural and evolutionary history of the disease must be known and the various forms defined"." Between ages of 50 and 74, lung cancers are therefore mainly composed of adenocarcinomas, which seem to be the most easily detectable. For example, in the European NELSON trial, 61% of cancers in the screened group are adenocarcinomas compared to 44% in the control group, which could explain a better effect of screening in women," explains the Academy.

    - Unknowns: on target population, on appropriate participation rate, frequency of scans, therapeutic indications for cancers discovered during the scan, acceptability by patients, motivation and compliance with smoking cessation, etc...

    - People who participate in the trials are not representative of entire population eligible for screening at a later date, which may lead to an overestimation of efficacy in the Nelson study.

    - Economic evaluation is also necessary, with the Academy correctly pointing out that primary prevention is certainly more effective and less costly.

To rebound on the arguments of the Academy of Medicine, it is necessary to bear in mind economic stakes of this screening, not only of the initial examination but also the high cost of iterative examinations in case of intermediate nodules (which must be followed over years to monitor their evolution). Bronchial cancer screening by CT would be 4 times more expensive than breast cancer screening and 10 times more expensive than colorectal cancer screening.

Specifically concerning women

The results on the effectiveness of low-dose CT screening at 10 years are more variable and difficult to interpret in women. The Academy also has reservations, particularly in the NELSON trial, pointing out that they are not significant because of the small number of women included in the two trials and followed up in 10 years.

For our part, we emphasize that this screening, if it is launched in the female smoking population, will be superimposed on the biennial mammography, again in total ignorance of the effect of cumulative doses of iterative examinations [7] [8] for an unproven reduction in mortality [9].

Irradiation draws attention again

Once again, and just as for breast cancer screening, let's keep in mind that we are inflicting radiation, even in low doses, on people who have no complaints, who are a priori healthy, and this radiation will be repeated.

For suspicious (5 to 10 mm) and undetermined nodules, a check-up will be carried out at 3 months. Nodules that increase in volume (+ 25% in volume in 3 months) and nodules larger than 10 mm must be investigated immediately (biopsy or surgery). Stable nodules will be controlled for 3 years.

Some semi-solid nodules may be slow-growing and will be followed for a longer period of time, for 5 years.

All this for a zero gain in terms of overall mortality.

Ionizing radiation induces two types of effects: "deterministic effect", i.e. conditioned directly and with certainty according to the dose of radiation received, for example if a certain threshold is exceeded as in the case of a nuclear catastrophe or during radiotherapy treatments.

The other effect is "random" (appearance of cancers with a certain probability for an individual but without certainty, without a known threshold, depending on individual radiosensitivity).

For diagnostic radiology, the doses used are certainly much lower compared to radiotherapy, but the exposure, especially repetitive, could be harmful in a "probabilistic" way, by an accumulation of alterations of cellular DNA and individual sensitivity. Since most estimates are based on extrapolations of risks observed from nuclear and atomic accidents, long-term effects of even minimal and repeated doses are certainly very variable depending on the individual, and definitely still unknown at the present.

On this subject, read the work of N. Foray, radiobiologist, INSERM.

https://www.sfmn.org/drive/CONGRES/JFMN/2016%20GRENOBLE/SCIENTIFIQUE/CommunicationsOrales/N._FORAY_MembreWeb.pdf

et https://its.aviesan.fr/getlibrarypublicfile.php/cd704e89988a4e3bcf2e1217566876cf/inserm/_/collection_library/201800012/0001/J1-098ITS-2017.foray.lyon.ITMO.TS..21.nov.2017.pdf.pdf

To conclude

For academics, the most important thing is the fight against the main risk factor: smoking, and acceptance of its reduction is the very condition for candidates selected for eventual regular screening.

Chest CT scans could then serve as a motivation for smoking patients to make a decision to quit.

It will then no longer be a matter of systematic screening of an entire population, but rather of using imaging as part of a smoker's health check-up, and as part of the singular colloquium within the medical consultation.

Finally, in the context of recognized occupational exposures, low-dose chest CT scans could be a method of monitoring exposed subjects.

Reactions

They were not long in coming, an APM dispatch of February 24, 2021 informs us that three learned societies are taking a stand.

"The three learned societies are the Francophone Thoracic Cancer Intergroup, the French Lung Society and the Thoracic Imaging Society.

In this text, which updates previous recommendations, the learned societies reaffirm their position in favor of individual screening by low-dose thoracic CT scan without injection of contrast agent, for which they specify the modalities." ......
" Contrary to the Academy of Medicine, which proposes a low-dose scanner once, during a smoker's health check-up, learned societies envisage a recurrent examination. They believe that there should be 2 CT scans one year apart and then one every 2 years, except in the case of risk factors or a previous exam with an intermediate result or it should continue every year.
And this screening should be continued "for a minimum period of at least 5.5 to 10 years".

Again, we note the regrettable and not very scientific reaction of the president of the National Federation of Radiological Doctors:

His text :

"Incompetence or senility? The National Academy of Medicine has rendered a verdict against the use of low-dose CT scanners for the detection of bronchopulmonary cancer. The scanner would contribute to the health assessment of smokers and help them quit smoking."

References

[1] http://www.thema-radiologie.fr/actualites/2592/l-etude-nelson-promeut-le-depistage-du-cancer-du-poumon-par-scanner.html

[2] https://www.has-sante.fr/upload/docs/application/pdf/2014-12/note_de_cadrage_cancer_du_poumon.pdf

[3] https://www.nejm.org/doi/full/10.1056/NEJMoa1911793

[4] This "gain" is often expressed as a relative reduction in the risk of dying, i.e. by comparing a screened group with an unscreened group.

In the case of breast cancer, the manipulation is to express this gain repeatedly, in particular in the media, in percentages. Thus you are told that breast cancer screening reduces mortality by 20%, everyone understands that 20 people out of every 100 screened die of this cancer, but this is not the case, in absolute figures there is only one life saved. Out of a group of 2000 women screened in 10 years, there is one death from breast cancer, out of a group of 2000 women not screened in 10 years, there are 5 deaths, the reduction from 5 to 4 is indeed a reduction of 20%, but in real life, it is only one person.…

[5] https://www.academie-medecine.fr/le-depistage-du-cancer-du-poumon-par-scanner-thoracique-faible-dose-stfd-reste-non-justifie-mais-peut-etre-utile-pour-un-bilan-de-sante-des-fumeurs/

[6] https://cancer-rose.fr/wp-content/uploads/2021/02/RAPPORT-Académie-de-médecine.pdf

[7] http://agora.qc.ca/documents/radiation_des_depistages_aux_accidents_nucleaires

[8] https://cancer-rose.fr/en/2020/12/15/radiotoxicity-and-breast-cancer-screening-caution-caution-caution/

[9]https://cancer-rose.fr/2019/10/20/le-depistage-de-masse-du-cancer-du-sein-bafoue-les-valeurs-ethiques-et-les-principes-fondamentaux-du-systeme-de-radioprotection/

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