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.

Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers.

A decreased transfer coefficient of the lung for carbon monoxide (K(CO)) is associated with emphysema. We evaluated whether in heavy smokers, baseline K(CO) was associated with the progression of computed tomography (CT)-detected emphysema, and the progression of airflow limitation. Heavy smokers, mean ± sd 41.3 ± 18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th-75th percentile) 2.8 (2.7-3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association between K(CO) at baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV1/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker). 522 participants aged 60.1 ± 5.4 yrs were included. Mean ± sd 15th percentile was -938 ± 19, absolute FEV1/FVC was 71.6 ± 9% and K(CO) was 1.23 ± 0.25, which is 81.8 ± 16.5% of predicted. By interpolation, a one sd (0.25) lower K(CO) value at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV1/FVC after follow-up (p < 0.001). A lower baseline K(CO) value is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.

Long-term effects of lung cancer computed tomography screening on health-related quality of life: the NELSON trial.

The long-term effects of lung cancer computed tomography (CT) screening on health-related quality of life (HRQoL) have not yet been investigated. In the Dutch-Belgian Randomised Lung Cancer Screening Trial (NELSON trial), 1,466 participants received questionnaires before randomisation (T0), 2 months after baseline screening (screen group only; T1) and at 2-yr follow-up (T2). HRQoL was measured as generic HRQoL (12-item short-form questionnaire and EuroQoL questionnaire), anxiety (Spielberger State-Trait Anxiety Inventory) and lung cancer-specific distress (impact of event scale (IES)). Repeated measures of ANOVA were used to analyse differences between the screen and control groups, and between indeterminate (requiring a follow-up CT) and negative screening result groups. At T0 and T2 there were no significant differences in HRQoL scores over time between the screen and control groups, or between the indeterminate or negative second-round screening result group. There was a temporary increase in IES scores after an indeterminate baseline result (T0: mean 4.0 (95% CI 2.8-5.3); T1: mean 7.8 (95% CI 6.5-9.0); T2: mean 4.5 (95% CI 3.3-5.8)). At 2-yr follow-up, the HRQoL of screened subjects was similar to that of control subjects, the unfavourable short-term effects of an indeterminate baseline screening result had resolved and an indeterminate result at the second screening round had no impact on HRQoL.

Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON).

BACKGROUND: In lung cancer CT screening, participants often have an indeterminate screening result at baseline requiring a follow-up CT. In subjects with either an indeterminate or a negative result after screening, we investigated whether health-related quality of life (HRQoL) changed over time and differed between groups in the short term. METHODS: A total of 733 participants in the NELSON trial received four questionnaires: T0, before randomisation; T1, 1 week before the baseline screening; T2, 1 day after the screening; and T3, 2 months after the screening results but before the 3-month follow-up CT. HRQoL was measured as generic HRQoL (the 12-item Short Form, SF-12; the EuroQol questionnaire, EQ-5D), anxiety (the Spielberger State-Trait Anxiety Inventory, STAI-6), and lung-cancer-specific distress (the Impact of Event Scale, IES). For analyses, repeated-measures analysis of variance was used, adjusted for covariates. RESULTS: Response to each questionnaire was 88% or higher. Scores on SF-12, EQ-5D, and STAI-6 showed no clinically relevant changes over time. At T3, IES scores that were clinically relevant increased after an indeterminate result, whereas these scores showed a significant decrease after a negative result. At T3, differences in IES scores between the two baseline result groups were both significant and clinically relevant (P<0.01). CONCLUSION: This longitudinal study among participants of a lung cancer screening programme showed that in the short term recipients of an indeterminate result experienced increased lung-cancer-specific distress, whereas the HRQoL changes after a negative baseline screening result may be interpreted as a relief.

A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer.

PURPOSE: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m(2) on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). METHODS: Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. RESULTS: 71 patients were enrolled into the study. We found 79% (95% CI 61-91%) grade 3-4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32-68%) in arm B; 66% grade 3-4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7-38.6%) was seen, and 18.2% (95% CI 7-35.5%) in arm B. CONCLUSIONS: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3-4 neutropenia and thrombocytopenia with comparable dose intensity and RR.

Pre-operative pulmonary evaluation of lung cancer patients: a review of the literature.

Complete anatomical resection of the primary tumour is still the standard of care in patients with early stage lung cancer. Because these patients are usually smokers who also suffer from chronic obstructive pulmonary disease, regional differences in pulmonary function due to lung tissue destruction exist. The purpose of the present article is to evaluate the currently available guidelines and to discuss novel methods for the pre-operative functional and anatomical pulmonary evaluation in lung cancer patients. Despite the fact that knowledge on the pre-operative evaluation of the pulmonary function has substantially increased during the past decade, the majority of the studies are small, underpowered and, with exception of a proposed algorithm, not prospectively validated in independent cohorts. The future harmonisation of guidelines is required and novel imaging techniques should be incorporated in the pre-operative evaluation in chronic obstructive pulmonary disease patients with borderline pulmonary function.

Informed participation in a randomised controlled trial of computed tomography screening for lung cancer.

The actual lung cancer (screening) knowledge, attitudes, risk perceptions, reasons to participate in or decline participation, and informed decisions of subjects who decided to or decided not to participate in the Dutch-Belgian randomised controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) were evaluated. A total of 2,500 high-risk subjects were asked to complete a questionnaire 3 weeks after they had received a brochure with information about the trial. Differences in knowledge, attitude and risk perception between participants and nonparticipants were analysed with logistic regression analyses adjusted for sex and smoking status. The questionnaire response of trial participants was 80% (n = 889) whereas the response of nonparticipants was low (7%, n = 97) and selective. Participants' responses to knowledge items on lung cancer as a disease were on average more often correct (mean+/-sd 68+/-17%) than items on lung cancer screening (49+/-29%). Participants had adequate knowledge on lung cancer screening (51%) more often than the nonparticipants (38%; p = 0.009). Of the decisions regarding participation, 49% were uninformed, mainly due to insufficient knowledge. Most of the participants (99%) and 64% of the nonparticipants had a positive attitude towards lung cancer screening. Additional efforts are required to improve the knowledge and understanding of subjects who are in the process of decision-making regarding participation in a lung cancer screening trial.

[Multi-detector CT screening for lung cancer is still to be discouraged for the time being]. / Screenen op longkanker met de multidetector-CT: voorlopig nog af te raden.

Lung cancer is an important public health problem with almost no improvement in survival over the past decades. Although observational studies demonstrate that low-dose multi-detector spiral-CT screening is able to detect lung cancer in an early stage in 55-85% of all cancer cases detected, and that 5- and even 10-year survival rates close to 90% can be achieved, these studies do not answer the question whether CT screening is advisable. Excellent survival rates in a few individuals do not necessarily indicate that there is a lung cancer-specific reduction in mortality, since observational studies are subject to several biases: lead time bias, over-diagnosis bias, and length time bias. Therefore, there is a strong worldwide recommendation from various professional organisations not to adopt CT screening for lung cancer on a wide scale, but to await the results from large randomised studies such as the US 'National lung screening trial' and the Dutch-Belgian-Danish 'Netherlands-Louvain lung cancer screening study' (NELSON), which will provide more clarity as to the effectiveness and cost-effectiveness and possible negative effects of CT screening for lung cancer.

Lessons to learn from EORTC study 08981: a feasibility study of induction chemoradiotherapy followed by surgical resection for stage IIIB non-small cell lung cancer.

The present EORTC phase II feasibility study in stage IIIB (T4-N3) NSCLC was conducted to investigate whether an induction regimen with concurrent chemoradiotherapy followed by surgery after restaging by re-mediastinoscopy and/or fluorodeoxyglucose-positron emission tomography (FDG-PET) was feasible in a multicenter setting. Unfortunately, the study closed prematurely because of poor accrual. The combination of more stringent selection criteria, the incorrect prevailing view of Ethical Boards that a tri-modality approach is too toxic, competing studies in the participating centers and the fact that patients with N3 disease could only be enrolled if a re-mediastinoscopy could be performed, underlie the low accrual. Although this study illustrates that the conduct of a tri-modality study across Europe appeared to be difficult at that time, the number of centers with highly qualified and experienced specialists involved in this kind of multi-modality approaches is rapidly increasing. Future initiatives should, therefore, certainly be encouraged. Minimally invasive procedures such as EUS and EBUS should preferably be used for up-front mediastinal staging, mediastinoscopy with or without EUS should preferably be reserved for restaging, and especially right-sided pneumonectomies should be avoided. Though evident, the feasibility to complete this kind of studies within a reasonable time period is still a condition sine qua non.

Prognostic factors in non-small cell lung cancer surgery.

AIMS: Complete surgical resection of primary tumours remains the treatment with the greatest likelihood for survival in early-stage non-small cell lung cancer (NSCLC). Although TNM stage is the most important prognostic parameter in NSCLC, additional parameters are required to explain the large variability in postoperative outcome. The present review aims at providing an overview of the currently known prognostic markers for postoperative outcome. METHODS: We performed an electronic literature search on the MEDLINE database to identify relevant studies describing the risk factors in NSCLC surgery. The references reported in all the identified studies were used for completion of the literature search. RESULTS: Poor pulmonary function, cardiovascular disease, male gender, advanced age, TNM stage, non-squamous cell histology, pneumonectomy, low hospital volume and little experience of the surgeon were identified as risk factors for postoperative outcome. However, with the exception of TNM stage and extent of resection, the literature demonstrates conflicting results on the prognostic power of most factors. The role of molecular biological factors, neoadjuvant treatment and adjuvant treatment is not well investigated yet. CONCLUSIONS: The advantage of knowing about the existence of comorbidity and prognostic risk factors may provide the clinician with the ability to identify poor prognostic patients and establish the most appropriate treatment strategy. The assessment of prognostic factors remains an area of active investigation and a promising field of research in optimising therapy of NSCLC patients.

Putrescine uptake in rat type II pneumocytes correlates with gamma-glutamyltransferase activity.

gamma-Glutamyltransferase (gamma GT) is a key enzyme in glutathione metabolism and it is thought also to play a role in the uptake of polyamines such as putrescine. The aim of our study was to investigate if changes in gamma GT activity would alter total putrescine uptake [P(up)(tot)], as well as more specific uptake via the gamma GT pathway [P(up)(gamma GT)]. Forty-eight hours after their isolation, rat type II cells were exposed to 30, 60 or 125 microM L-buthionine-[SR]-sulfoximine (BSO) for 3 hr; 200 or 800 microM tertiary-butylhydroperoxide (t-BOOH) for 40 min; 10, 100 or 1000 microM paraquat (PQ) for 1 hr; and 60 or 85% O2 for 48 hr. The gamma GT activity, P(up)(tot) and P(up)(gamma GT) (assessed by inhibiting gamma GT) were measured immediately after the exposure to hyperoxia, or 24 hr after treatment with BSO, t-BOOH or PQ. From previous studies, it is known that these experimental conditions increased (BSO, 200 microM t-BOOH) or decreased (800 microM t-BOOH, PQ, hyperoxia) gamma GT activity. There was a strong correlation between the changes in gamma GT activity and the changes in P(up)(gamma GT) (r = 0.81, p < 0.001). These findings support the hypothesis that gamma GT partly regulates the uptake of putrescine, one of the polyamines required for cell growth and differentiation.

Increase in gamma-glutamyltransferase by glutathione depletion in rat type II pneumocytes.

The purpose of our study was to investigate the effect of oxidative stress or intracellular glutathione (GSH) depletion on gamma-glutamyltransferase (gamma-GT) activity in cultured type II pneumocytes. Twenty-four hours after isolation, primary cultures of rat type II pneumocytes were preincubated with one of four compounds: 15, 30, 60, 125, 250 microM L-buthionine-[SR]-sulfoximine (BSO) for 3 h; 100, 200, 400, 800 microM tertiary-butylhydroperoxide (t-BOOH) for 45 min; 10, 25, 50, 100 microM menadione for 15 min; 100, 1000 microM paraquat for 1 h. GSH levels, H2O2 and O2.- generation were measured immediately after the incubation, gamma-GT activity and GSH levels also up to 24 h or 48 h later. Exposure to BSO led to a persistent GSH depletion without increase in H2O2 or O2.- production, together with a dose and time-dependent increase (doubling) of gamma-GT activity with a nonsignificant increase in gamma-GT mRNA expression 24 h after exposure to BSO. Exposure to 100 microM menadione, which increased H2O2 production, decreased gamma-GT activity. t-BOOH or paraquat did not give rise to a measurable increase in H2O2 or O2.-. Paraquat did not affect initial GSH levels, but increased GSH and decreased gamma-GT activity 24 h later. t-BOOH (400 and 800 microM) initially decreased GSH, and tended to increase GSH 24 h later, 100 and 200 microM increased gamma-GT activity 24 h later, but 800 microM decreased it. Restoration of intracellular GSH levels by addition of GSH to the culture medium completely prevented the increase in gamma-GT activity by BSO, while the addition of catalase or DMTU had no effect. We conclude that at least two effects are operating upon gamma-GT activity: GSH depletion seems to increase gamma-GT activity, while exposure to compounds generating oxidative stress correlates with a decrease in gamma-GT activity.

A phase II EORTC study of temozolomide in patients with malignant pleural mesothelioma.

The aim of this study was to investigate the anti-tumour activity of temozolomide in patients with malignant pleural mesothelioma. 27 chemotherapy-naïve patients with histologically-proven malignant mesothelioma were treated with temozolomide 200 mg/m2/day, given orally on days 1-5 of each 28-day cycle. Therapy continued up to 10 cycles unless disease progression or excessive toxicity mandated discontinuation. Toxicity, symptom improvement and pain intensity were regularly assessed. With a median relative dose intensity of 97%, toxicity was moderate with grade 3 or more nausea, vomiting, thrombocytopenia, leucocytopenia, neutropenia, febrile leucocytopenia, arthralgia, infection and fever with infection occurring in 13, 13, 10, 3, 7 and 3% of patients for the remaining events, respectively. Overall, 1 objective response was observed (response rate 4%, 95% Confidence Interval (CI): 0.1-19). Median survival was 8.2 months. Symptom assessment showed no improvement and an increase of pain was observed during the study. Thus, oral temozolomide is an inactive agent in malignant mesothelioma.

Role of gamma-glutamyltransferase in putrescine uptake by rat type II pneumocytes.

Putrescine uptake in type II pneumocytes is a carrier-mediated active process. Our hypothesis was that oligoamines might be taken up into the cell at least in part by gamma-glutamyltransferase (gamma-GT). This was investigated in rat type II pneumocytes 24 hr after their isolation. Preexposure to 125 microM L-buthionine-[SR]-sulfoximine (BSO) or 100 microM diethylmaleate (DEM), both of which affect intracellular glutathione (GSH) only, were found to decrease GSH by 85% (p < 0.05) and 62%, respectively (p < 0.05), without change in [3H]-putrescine uptake. Preexposure to 20 microM N-ethylmaleimide (NEM), which affects intra- and extracellular GSH, decreased intracellular GSH by 79% (p = 0.015) and putrescine uptake by 39% (p = 0.03). Selective extracellular GSH depletion by 10 microM copper-o-phenanthroline complex (CuP) led to a decrease in putrescine uptake of 41% (p = 0.001), while intracellular GSH remained unchanged. Specific inhibition of gamma-GT by 5-20 mM serine-borate or 5 mM acivicin gave similar degrees of putrescine uptake inhibition (39.5% and 40.5%). The kinetic properties of the putrescine uptake system in the presence of acivicin and serine-borate indicated that the Vmax decreased by 25%, while Km remained unchanged. In experiments with pure gamma-GT, the oligoamines putrescine, spermidine and spermine, and cystamine proved to be acceptor substrates for gamma-GT, all having similar efficiencies (Vmax/Km); methylglyoxal-bis-(guanyl-hydrazone) and paraquat were not accepted. As extracellular GSH is required for gamma-GT, and because its extracellular depletion inhibits putrescine uptake as much as specific inhibition of gamma-GT, we suggest that 30-40% of the putrescine uptake in type II pneumocytes occurs by gamma-GT and that, therefore, at least two systems are involved in the uptake of putrescine.

Prognosis of unsuspected but completely resectable N2 non-small cell lung cancer.

Of 111 patients with non-small cell lung cancer without clinically evident N2 disease 95 underwent mediastinoscopy between 1975 and 1985. In 63 cases mediastinoscopy was positive and in 32 negative. The patients with a positive mediastinoscopy were considered to have inoperable disease. Their 3- and 5-year survival rates were 5% and 0%, respectively. The patients with a negative mediastinoscopy and 16 patients in whom no mediastinoscopy was performed because of a peripheral tumor underwent operation. They underwent complete tumor resection and mediastinal lymph node dissection. Unsuspected N2 disease was found. Their 3- and 5-year survival rates were 19% and 10%, respectively. The better survival rate in the operated group was statistically significant and mainly due to a better survival of the lobectomy group. Multiple regression analysis showed no favorable prognostic factors in the nonoperated group, but in the operated group lobectomy and central location of the tumor significantly improved the prognosis. We conclude that patients with unsuspected stage IIIa non-small cell lung cancer discovered at thoracotomy benefit from complete tumor resection and mediastinal lymph node dissection, especially if the resection can be confined to lobectomy and if the tumor is located centrally.

Investigation of the transport of intact glutathione in human and rat type II pneumocytes.

The aim of the study was to investigate whether there is transmembrane transport of intact glutathione ([3H]-GSH, 0.1 microCi) in rat and human type II pneumocytes (T2P), and if this transport might be dependent on the redox state of the extracellular fluid. The T2P were pretreated with acivicin (250 microM) to inhibit gamma-glutamyltransferase activity and with L-buthionine-[SR]-sulfoximine (1 mM) to inhibit intracellular GSH synthesis. After 48 h in culture, initial GSH influx rate was 0.70 +/- 0.20 nmol/min/mg protein (37 degrees C) and 0.35 +/- 0.04 nmol/min/mg protein (4 degrees C) during the first 5 min in rat T2P. In human T2P, the initial GSH influx rate was 0.36 +/- 0.30 nmol/min/mg protein (37 degrees C) and 0.32 +/- 0.06 nmol/min/mg protein (4 degrees C) during the first 10 min. Thereafter no further influx was found. The influx of 1 mM GSH in freshly isolated rat and human T2P in suspension was 2.3 +/- 0.3 and 1.2 +/- 0.3 nmol/mg protein after 15 min at 37 degrees C, and 2.8 +/- 0.2 and 1.0 +/- 0.3 nmol/mg protein at 4 degrees C, respectively. When GSH influx was studied at different concentrations between 0 and 40 mM, a linear increase without saturation or difference between 37 degrees C and 4 degrees C was found. Pre-exposure to ouabain had no effect on GSH influx. Efflux of GSH was stimulated and influx inhibited by pre-exposure of the cells to reduced thiols, while disulphides inhibited efflux and favoured inward uptake. Thus, in human and rat T2P a GSH-carrier exists which operates as an effluxer. At GSH concentrations in the physiological range no uptake is seen, but some uptake can be observed at GSH concentrations above normal physiological levels. The uptake appears to be energy-independent and non-saturable. Efflux of GSH is stimulated and influx inhibited by reduced thiols, while disulphides inhibit the efflux and favour inward uptake. GSH uptake in T2P thus may depend on concentration gradients and driving forces, such as the redox state of the extracellular fluid.

[Deposition of light chains in various organs; light chain deposition disease]. / Neerslag van lichte ketens in verscheidene organen; 'light chain deposition disease'.

The case is reported of a patient with renal insufficiency, proteinuria and heart failure caused by 'light chain deposition disease' (LCDD). A renal biopsy showed nodular glomerulosclerosis, IF examination revealed linear deposits of monoclonal lambda light chains along the glomerular and tubular basement membranes. Similar deposits could be shown in a skin biopsy. No light chains could be detected in urine and serum. The patient had a good response to treatment with melphalan and prednisone.

[The central venous catheter in the treatment of patients with malignancies]. / De centraal-veneuze catheter bij de behandeling van patiënten met een maligniteit.

This review describes the role of central venous catheters (CVC's) in the treatment of cancer. Indications and contra-indications for CVC-insertion, CVC-care, their complications, prevention and management are discussed. Totally implantable CVC's have been compared with Hickman-Broviac catheters to facilitate an adequate choice for an individual patient. Both CVC-types showed a similar and low number of complications, provided staff and patients are well instructed and given good care. In such cases infection and thrombosis occur in less than 3-5% of nowadays CVC's. The CVC proved to be useful and safe in cancer treatment and should not be withheld when the patient lacks, or will probably lack within a short time an adequate venous access.

[Generalized sarcoidosis in combination with a malignancy in 3 patients; the value of mediastinoscopy]. / Gegeneraliseerde sarcoïdose in combinatie met een maligniteit bij 3 patiënten; de waarde van mediastinoscopie.

Two male patients with a testicular carcinoma and a female with a mammary carcinoma, all associated with pulmonary sarcoidosis are described. This coincidence is very rare, but clinically relevant as enlarged mediastinal and hilar lymph nodes might suggest metastatic disease or metastasis after a curative treatment. The role of mediastinoscopy in obtaining a histological diagnosis is stressed. A causal relationship between sarcoidosis and malignant diseases has not yet been established.

[Screening for lung cancer in the Netherlands: the role of spiral CT scan]. / Longkankerscreening in Nederland: de rol van spiraal-CT.

The very poor prognosis of lung cancer has barely changed in the last two decades despite all efforts. However, prognosis is better when the disease is detected earlier, so that curative surgery or radiotherapy can be applied. Lung cancer screening in the past by chest X-ray did not lead to a decrease in lung cancer mortality, because the chest X-ray has low sensitivity for early invasive stages. With the advent of the low-dose spiral CT scan it has become feasible to detect early invasive stage I lung cancer in 80-90%. Modern screening for lung cancer by spiral CT scan could possibly decrease lung cancer mortality. Despite the first favourable results of screening the question remains whether lung cancer screening will be cost-effective. These questions can only be resolved in a randomised controlled trial with lung cancer mortality as unbiased end-point. Such a study should be initiated in the Netherlands, a country with large experience in screening trials and a good health care system. Only after lung cancer screening has proven to be cost-effective can appropriate implementation be recommended to prevent uncontrolled and opportunistic diffusion of this new screening technique into clinical practice in the near future.