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.

Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome. METHODS: Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response. RESULTS: Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate. CONCLUSIONS: The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.

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.

Dual-energy CT angiography for assessment of regional pulmonary perfusion in patients with chronic thromboembolic pulmonary hypertension: initial experience.

OBJECTIVE: This study assessed the utility of dual-energy pulmonary CT angiography (CTA) for noninvasive assessment of regional pulmonary perfusion in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Regional perfusion abnormalities were correlated with hemodynamic parameters and structural abnormalities on pulmonary CTA. SUBJECTS AND METHODS: Twenty patients with CTEPH (11 men and nine women; mean age, 61.5 years) underwent pulmonary CTA with a dual-energy technique. Right heart catheterization data were available in 15 cases. Scan parameters were as follows: tube A, 140 kV (75 mA); tube B, 80 kV (300 mA); gantry rotation, 500 milliseconds; pitch, 0.5; and collimation, 14 × 1.2 mm. An iodine map was generated via three-material-decomposition and was scored for extent of hypoperfusion. Correlation was made with mosaic attenuation pattern, extent of vascular obstruction, and right heart hemodynamics. Iodine attenuation values were analyzed within completely occluded, partially occluded, and disease-free lobes. RESULTS: A strong correlation existed between dual-energy CT-derived perfusion and mosaic attenuation pattern when both lobar (r > 0.6; n = 20; p < 0.006) and whole-lung scores were assessed (r = 0.77; n = 20; p < 0.001). There was no statistically significant correlation between dual-energy CT perfusion and vascular obstructive index, mean pulmonary artery pressure, or pulmonary vascular resistance (p > 0.08). Of 42 completely occluded lobes, 27 (64%) had demonstrable residual perfusion (mismatching), suggesting that blood supply was maintained via systemic collaterals. CONCLUSION: Dual-energy CT can offer a "one-stop" assessment of anatomy and perfusion in CTEPH. The additional information provided by dual-energy CT could have a future role in helping guide patient selection for thromboendarterectomy surgery.

Cardiac causes of pulmonary arterial hypertension: assessment with multidetector CT.

The causes of pulmonary arterial hypertension (PAH) are diverse and include multiple congenital and acquired cardiac diseases as well as diseases primarily affecting the pulmonary vasculature, lung, pleura and chest wall. The traditional role of CT in evaluating PAH includes assessment of pulmonary vasculature and lung parenchyma with limited assessment of the heart. Advances in multidetector CT technology with improved spatial and temporal resolution now permit accurate delineation of cardiac morphology. CT pulmonary angiography (CTPA) is widely utilised in the workup of patients with suspected pulmonary vascular disease and can identify both pulmonary and cardiac causes. As the initial presentation for CTPA is often precipitated by nonspecific, unexplained symptoms and therefore undertaken by a general radiologist, it is important that a systematic approach to the interpretation of these studies, including cardiac evaluation, is routinely adopted. This paper reviews the CT evaluation in pulmonary hypertension with a particular focus on the cardiac causes, their subclassification into congenital systemic to pulmonary shunts and secondary to left heart disease, and their imaging features. It emphasises the use of a systematic approach to interpretation of CTPA examinations both in patients with known PAH and those with previously unsuspected disease.