Uniform and blinded cause of death verification of the NELSON lung cancer screening participants.

Primary outcome of the Dutch-Belgian lung cancer screening trial (NELSON) is lung cancer-specific mortality. Accurate assessment of the cause of death (CoD) is crucial. As death certificates regarding the CoD can be inaccurate, a clinical expert committee (CEC) was formed to assign the CoD. In this study, the medical files of deceased lung cancer patients were reviewed and the outcomes were compared with official death certificates. The first 266 completed medical files of Dutch deceased participants who were diagnosed with lung cancer during the study or of those with lung cancer on the death certificate were selected and blinded towards arms and patients identity. The end product of the review process consisted of six possible categories which defined the graduation of certainty that lung cancer was the primary CoD. The percentage agreement and the Cohen's kappa statistics between the two CEC-memberswere calculated. The sensitivity and specificity of the official death certificates were determined. The results indicated that, the overall concordance and the Cohen's kappa between the CEC-memberswere 86.1% and 0.57(0.45-0.69, p<0.001), respectively. This level increased with the numbers of cases evaluated. The sensitivity and the specificity of the official death certificate were 92.6% and 98.8%; 6.5% cases were reclassified to lung cancer specific death, which is lower than in the National Lung Screening trial(22.0%). Concluding, each death should be reviewed by at least two members. So far, in the NELSON trial, possible biases related to lung cancer death seem relatively small.

Bone density loss on computed tomography at 3-year follow-up in current compared to former male smokers.

OBJECTIVES: Cigarette smoking negatively affects bone quality and increases fracture risk. Little is known on the effect of smoking cessation and computed tomography (CT)-derived bone mineral density (BMD) decline in the spine. We evaluated the association of current and former smoking with BMD decline after 3-year follow-up. METHODS: Male current and former smokers participating in a lung cancer screening trial who underwent baseline and 3-year follow-up CT were included. BMD was measured by manual placement of a region of interest in the first lumbar vertebra and expressed in Hounsfield Unit (HU). Multiple linear regression analysis was used to evaluate the association between pack years smoked and smoking status with BMD decline. RESULTS: 408 participants were included with median (25th-75th percentile) age of 59.4 (55.9-63.5) years. At the start of the study, 197 (48.3%) participants were current smokers and 211 (51.7%) were former smokers and had a similar amount of pack years. Current smokers had quit smoking for 6 (4-8) years prior to inclusion. There was no difference in BMD between current and former smokers at baseline (109±34 HU vs. 108±32 HU, p=0.96). At 3-year follow-up, current smokers had a mean BMD decline of -3±13 HU (p=0.001), while BMD in former smokers did not change as compared to baseline (1±13 HU, p=0.34). After adjustment for BMD at baseline and body mass index, current smoking was independently associated with BMD decline (-3.8 HU, p=0.003). Age, pack years, and the presence of a fracture at baseline did not associate with BMD decline. CONCLUSIONS: Current smokers showed a more rapid BMD decline over a 3-year period compared to former smokers. This information might be important to identify subjects at risk for osteoporosis and emphasizes the importance of smoking cessation in light of BMD decline.

Generalisability of the results of the Dutch-Belgian randomised controlled lung cancer CT screening trial (NELSON): does self-selection play a role?

The degree of self-selection in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON) was determined to assess the generalisability of the study results. 335,441 (mainly) men born in 1928-1953 received a questionnaire. Of the respondents (32%), eligible subjects were invited to participate (19%). Fifty-five percent gave informed consent and was randomised. Background characteristics were compared between male respondents on the first questionnaire (n = 92,802), eligible subjects among them (n = 18,570) and those randomised (n = 10,627) and Statistics Netherlands 2002-2005 (SN) (n = 5289) or GLOBE study-data (Dutch cohort) (n = 696). Initial respondents were less likely to be highly educated (OR(adj) = 0.84; 95% CI: 0.74-0.96) and comprised of significantly less current smokers (OR(adj) = 0.65; 95% CI: 0.61-0.69) compared to the general population. These current smokers smoked more heavily (OR(adj) = 1.23; 95% CI: 1.10-1.37), but for a shorter time-period (respondents: 31, SN: 42 years, p < 0.001). Age, general health, BMI, alcohol use and cancer prevalence were comparable. The randomised population was younger (Age 50-65) (randomised subjects: 85.3%, SN: 72% (p < 0.01)) comprised of more heavy current smokers (OR = 2.08; 95% CI: 1.75-2.44), that smoked for a shorter period of time (randomised subjects: 37, SN_selection: 42 years (p < 0.001)). Both the respondents (32%) of the first questionnaire as well as the randomised population of the NELSON trial appeared to differ slightly on smoking characteristics, but the differences were limited and probably balance each other. Results of the NELSON trial will be roughly applicable to the Dutch and probably other populations that fulfil our selection criteria.

The impact of a lung cancer computed tomography screening result on smoking abstinence.

Receiving a lung cancer computed tomography screening result might be a teachable moment for smoking cessation, but it might also unintentionally reassure smokers to continue smoking. The objective of the present study was to investigate whether test results were associated with smoking abstinence in the Dutch-Belgian Randomised Controlled Lung Cancer Screening Trial (NELSON trial). Two random samples of male smokers who had received either only negative test results (n=550) or one or more indeterminate test result (n=440) were sent a questionnaire 2 yrs after randomisation. Smokers with an indeterminate result reported more quit attempts (p=0.02), but the prolonged abstinence rate in smokers receiving a negative test (46 (8.9%) out of 519 subjects) was comparable with the abstinence rate in smokers with one or more indeterminate results (48 (11.5%) out of 419 subjects) (p=0.19). A statistically insignificant increase was found after one or more indeterminate test result (10.9 and 15.0%, respectively) compared with receiving only negative test results (8.9%) (p=0.26). In conclusion, the outcome of the screening test had no impact on future smoking abstinence in male smokers, although all results suggest more favourable implications after one or more follow-up recommendations. Screening test outcomes could be used as a teachable moment for smoking cessation.

Does participation to screening unintentionally influence lifestyle behaviour and thus lifestyle-related morbidity?

Cancer is a leading cause of death worldwide and the burden could be reduced by evidence-based strategies for the primary prevention of cancer, the early detection of malignancies and more adequate treatment of cancer patients. Previous research has shown that lifestyle factors are associated with common cancers and that several cancer screening programmes are cost-effective in reducing cancer-specific mortality. But, some recent studies reported that participants of screening programs might unintentionally change their lifestyle. Cancer screening might be a teachable moment or, on the other hand, have a false health certificate effect. Despite that the evidence is scarce, cancer screening might have opportunities for lifestyle improvements, although a possible health certificate effect still remains. Integrated approaches to combine primary and secondary prevention have the potential to optimise the efforts to improve cancer prevention and survival. More research is warranted to investigate evidence-based approaches.