Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis.

BACKGROUND: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. METHODS: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. FINDINGS: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. INTERPRETATION: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. FUNDING: NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

The impact of trained radiographers as concurrent readers on performance and reading time of experienced radiologists in the UK Lung Cancer Screening (UKLS) trial.

OBJECTIVES: To compare radiologists' performance reading CTs independently with their performance using radiographers as concurrent readers in lung cancer screening. METHODS: 369 consecutive baseline CTs performed for the UK Lung Cancer Screening (UKLS) trial were double-read by radiologists reading either independently or concurrently with a radiographer. In concurrent reading, the radiologist reviewed radiographer-identified nodules and then detected any additional nodules. Radiologists recorded their independent and concurrent reading times. For each radiologist, sensitivity, average false-positive detections (FPs) per case and mean reading times for each method were calculated. RESULTS: 694 nodules in 246/369 (66.7%) studies comprised the reference standard. Radiologists' mean sensitivity and average FPs per case both increased with concurrent reading compared to independent reading (90.8 ± 5.6% vs. 77.5 ± 11.2%, and 0.60 ± 0.53 vs. 0.33 ± 0.20, respectively; p < 0.05 for 3/4 and 2/4 radiologists, respectively). The mean reading times per case decreased from 9.1 ± 2.3 min with independent reading to 7.2 ± 1.0 min with concurrent reading, decreasing significantly for 3/4 radiologists (p < 0.05). CONCLUSIONS: The majority of radiologists demonstrated improved sensitivity, a small increase in FP detections and a statistically significantly reduced reading time using radiographers as concurrent readers. KEY POINTS: • Radiographers as concurrent readers could improve radiologists' sensitivity in lung nodule detection. • An increase in false-positive detections with radiographer-assisted concurrent reading occurred. • The false-positive detection rate was still lower than reported for computer-aided detection. • Concurrent reading with radiographers was also faster than single reading. • The time saved per case using concurrently reading radiographers was relatively modest.

Comparing the performance of trained radiographers against experienced radiologists in the UK lung cancer screening (UKLS) trial.

OBJECTIVE: To compare the performance of radiographers against that of radiologists for CT lung nodule detection in the UK Lung Cancer Screening (UKLS) pilot trial. METHODS: Four radiographers, trained in CT nodule detection, and three radiologists were prospectively evaluated. 290 CTs performed for the UKLS were independently read by 2 radiologists and 2 radiographers. The reference standard comprised all radiologist-identified positive nodules after arbitration of discrepancies. For each radiographer and radiologist, relative sensitivity and average false positives (FPs) per case were compared for all cases read, as well as for subsets of cases read by each radiographer-radiologist combination (10 combinations). RESULTS: 599 nodules in 209/290 (72.1%) CT studies comprised the reference standard. The relative mean (±standard deviation) sensitivity of the four radiographers was 71.6 ± 8.5% compared with 83.3 ± 8.1% for the three radiologists. Radiographers were less sensitive and detected more FPs per case than radiologists in 7/10 and 8/10 radiographer-radiologist combinations, respectively (ranges of difference 11.2-33.8% and 0.4-2.6; p < 0.05). In 3/10 and 2/10 combinations, there was no difference in sensitivity and FPs per case between radiographers and radiologists. For nodules ≥100 mm(3) in volume or ≥5 mm in maximum diameter, radiographers were relatively less sensitive than radiologists in only 5/10 radiographer-radiologist combinations (range of difference 16.1-30.6%; p < 0.05) and not significantly different in the remaining 5/10 combinations. CONCLUSION: Although overall radiographer performance was lower than that of experienced radiologists in this study, some radiographer performances were comparable with that of radiologists. ADVANCES IN KNOWLEDGE: Overall, radiographers were less sensitive than radiologists reading the same CTs and also displayed higher average FP detections per case when compared with a reference standard derived from radiologist readings. However, some radiographers compared favourably with radiologists, especially when considering larger potentially clinically relevant nodules. Thus, while probably not sensitive enough to function as first readers, radiographers may still be able to fulfil the role of an assistant reader-that is, as a first or concurrent reader, who presents detected nodules for verification to a reading radiologist.

The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.

BACKGROUND: Lung cancer kills more people than any other cancer in the UK (5-year survival < 13%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects. OBJECTIVES: To (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening. DESIGN: A pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥ 5% over 5 years). SETTING: Thoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire. PARTICIPANTS: Individuals aged 50-75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres. INTERVENTIONS: A thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria. MAIN OUTCOME MEASURES: Population-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling. RESULTS: A total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in the CT arm and 2027 in the control arm. A total of 1994 participants underwent CT scanning: 42 participants (2.1%) were diagnosed with lung cancer; 36 out of 42 (85.7%) of the screen-detected cancers were identified as stage 1 or 2, and 35 (83.3%) underwent surgical resection as their primary treatment. Lung cancer was more common in the lowest socioeconomic group. Short-term adverse psychosocial consequences were observed in participants who were randomised to the intervention arm and in those who had a major lung abnormality detected, but these differences were modest and temporary. Rollout of screening as a service or design of a full trial would need to address issues of outreach. The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality. CONCLUSIONS: The UK Lung Cancer Screening (UKLS) pilot was successfully undertaken with 4055 randomised individuals. The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60-75 years age group, selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocols. FUTURE WORK: The UKLS data will be pooled with the NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek: Dutch-Belgian Randomised Lung Cancer Screening Trial) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data. For now, there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery. Strategies for increasing uptake and providing support for underserved groups will be key to implementation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78513845. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 40. See the NIHR Journals Library website for further project information.

The UK Lung Screen (UKLS): demographic profile of first 88,897 approaches provides recommendations for population screening.

UNLABELLED: The UK Lung Cancer Screening trial (UKLS) aims to evaluate low-dose computed tomography (LDCT) lung cancer population screening in the United Kingdom. In UKLS, a large population sample ages 50 to 75 years is approached with a questionnaire to determine lung cancer risk. Those with an estimated risk of at least 5% of developing lung cancer in the next 5 years (using the Liverpool Lung project risk model) are invited to participate in the trial. Here, we present demographic, risk, and response rate data from the first 88,897 individuals approached. Of note, 23,794 individuals (26.8% of all approached) responded positively to the initial questionnaire; 12% of these were high risk. Higher socioeconomic status correlated positively with response, but inversely with risk (P < 0.001). The 50- to 55-year age group was least likely to participate, and at lowest cancer risk. Only 5% of clinic attendees were ages ≤60 years (compared with 47% of all 88,897 approached); this has implications for cost effectiveness. Among positive responders, there were more ex-smokers than expected from population figures (40% vs. 33%), and fewer current smokers (14% vs. 17.5%). Of note, 32.7% of current smokers and 18.4% of ex-smokers were designated as high risk. Overall, 1,452 of 23,794 positive responders (6.1%) were deemed high risk and attended a recruitment clinic. UKLS is the first LDCT population screening trial, selecting high-risk subjects using a validated individual risk prediction model. KEY FINDINGS: (i) better recruitment from ex- rather than current smokers, (ii) few clinic attendees ages early 50s, and (iii) representative number of socioeconomically deprived people recruited, despite lower response rates.

Proteus syndrome: high-resolution CT and CT pulmonary densitovolumetry findings.

Cystic transformation of the lungs in Proteus syndrome is considered an important manifestation of this disease. We describe a case of an 11-year-old girl with a diagnosis of Proteus syndrome with lung involvement. Low-dose multidetector computed tomography (CT) revealed extensive diffuse cystic lung disease with left lung predominance, affecting mostly the lower lung zones. The cystic lesions had various sizes and variable wall thickness. Postprocessing using CT histogram densitometric volumetry software (CT densitovolumetry), using the threshold -950 Houndsfield units (HU) for quantifying emphysema, revealed that 31% of her total lung volume was composed of areas with CT attenuation values below -950 HU.

Computed tomography measurement of lung volume in preoperative assessment for living donor lung transplantation: volume calculation using 3D surface rendering in the determination of size compatibility.

The objective of this study was to describe the use of CT volume quantification assessment of candidates for LLDLT. Six pediatric candidates for LDLLT and their donors were investigated with helical chest CT, as part of the preoperative assessment. The CT images were analyzed as per routine and additional post-processing with CT volume quantification (CT densitovolumetry) was performed to assess volume matching between the lower lobes of the donors and respective lungs of the receptors. CT images were segmented by density and region of interest, using post-processing software. Size matching was also assessed using the FVC formula. Compatible volumes were found in three cases. The other three cases were considered incompatible. All three recipients with compatible sizes survived the procedure and are alive and well. One patient with incompatible size was submitted to the procedure and died because of complications attributed to the incompatible volumes. One patient with incompatible size has subsequently grown and new measurements are to be taken to check the current volumes. Different donors are being sought for the remaining patient whose lung volumes were considered too big for the prospective transplant donor lobes. Under FVC formula criteria, all cases were considered compatible. CT volume quantification is an easy to perform, non-invasive technique that uses CT images for the preassessment of candidates for LDLLT, to compare the volume of the lower lobes from the donors with volume of each lung in the prospective recipients. Size matching based on CT densitovolumetry and FVC may differ.

Population screening for lung cancer.

The feasibility of diagnosing small stage 1 lung cancers using low-dose chest computed tomography in asymptomatic at-risk individuals has been demonstrated in multiple studies. However, it has yet to be proved that the introduction of a chest computed tomography screening programme would do more good than harm at an acceptable cost.

Two cases of rounded atelectasis presenting after coronary artery surgery.

Rounded atelectasis developed in two patients after coronary artery bypass grafting. Although both lesions led to the suspicion of a primary pulmonary tumor on initial assessment, malignancy was excluded by biopsy and radiologic observation in the first patient and excision biopsy in the second.