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Systematic review suggests emphysema on CT scan associated with higher risk of lung cancer

6th May 2022

The presence of visual or quantitative emphysema on a CT-scan is associated with a more than twofold increased risk of developing lung cancer, according to a recent study

The detection of emphysema via visual or quantitative assessment on a CT-scan has been found to be linked with a higher odds of developing lung cancer. This was the conclusion of a systematic review by researchers from the Departments of Epidemiology, Radiology and Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

The World Health Organization reported that in 2020 there were 2.21 million cases of lung cancer which resulted in 1.8 million deaths. A chest computer tomography (CT) scan enables quantification of the amount of emphysema present in the lungs and while some evidence suggests that emphysema on a CT scan is related to lung cancer in a high-risk population, other data indicates that no CT measures of emphysema have an independent association with lung cancer.

With some uncertainty over the association between the presence of emphysema seen on a CT scan and lung cancer, for the present study, the researchers decided to undertake a systematic review and meta-analysis to further probe this association. They searched all the major databases and included studies that specifically assessed the association between emphysema and the diagnosis of lung cancer based on histopathologic examination. The team defined visual emphysema as disrupted lung vasculature and parenchyma with low attenuation occupying any lung zone on the chest CT scan and quantitative emphysema as the percentage of total lung volume below a given Hounsfield unit threshold (-950 HU at full inspiration). They also sought to examine whether the severity of emphysema was associated with lung cancer and graded this as trace, mild, moderate/severe. The studies were stratified based on whether visual or quantitative assessments were used and the presence of confirmed lung cancer was the main outcome of interest expressed and expressed as an odds ratio, adjusted for age, gender and smoking status.

Emphysema and lung cancer risk

A total of 21 studies met the inclusion criteria with 3907 patients who had lung cancer and 103,175 controls.

The pooled odds ratio (OR) for lung cancer in the presence of emphysema was 2.3 (95% CI 2 – 2.6) in studies which employed visual assessment and 2.2 (95% CI 1.8 – 2.8) where the authors used quantitative assessment.

When stratified by disease severity, the overall pooled OR for lung cancer increased with disease severity although there were differences based on whether the data was acquired by visual or quantitative assessment. For example, in studies that employed visual assessment, the ORs for lung cancer were 2.5 (trace disease), 3.7 (mild disease) and 4.5 (moderate to severe disease). While these odds ratios were still elevated based on quantitative assessments, the magnitudes were slightly lower e.g., 1.9 for trace disease and 2.5 (moderate to severe disease).

Based on their findings, the author concluded that the presence of emphysema diagnosed on a chest CT scan was independently associated with a higher odds of developing lung cancer.

Citation
Yang X et al. Association between Chest CT–defined Emphysema and Lung Cancer: A Systematic Review and Meta-Analysis Radiology 2022

Smoking cessation at time of lung cancer diagnosis associated with improved survival

20th January 2022

Smoking cessation initiated around the time of a lung cancer diagnosis is associated with an improved overall survival from the disease

Smoking cessation at the time of a lung cancer diagnosis is linked to an improved survival from both non-small and small cell lung cancer, according to the findings of a systematic review by a team from the Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy

Data from the World Health Organization shows that in 2020, globally, there were 2.21 million cases of lung cancer and which led to 1.8 million deaths. In addition, lung cancer has a poor prognosis and Cancer Research UK suggests that only around 15% of those with lung cancer will survive for 5 years or more after diagnosis. Cigarette smoking is a major factor in the development of lung cancer, with one analysis of the burden of respiratory tract cancers indicating that smoking contributed to an estimated 64·2% of all deaths from tracheal, bronchus, and lung cancer and 63·4% of all deaths from larynx cancer in 2019.

Although one study with 517 smokers, found that smoking cessation at the time of a lung cancer diagnosis can reduce the risk of future lung cancer, for the present study, the Italian team sought to provide a more robust estimate of the overall prognostic value of smoking cessation at or around the time of a lung cancer diagnosis. They searched for articles which included those who continued to smoke and those who quit in relation to their cancer diagnosis and the associated changes in survival. The team calculated relative risks for the association between smoking cessation and the survival from lung cancer.

Findings

A total of 21 studies were included in the systematic review with patients diagnosed with non-small cell lung cancer (10 studies, 5315 patients) and small cell lung cancer (5 studies, 1133 patients), together with a further six studies of both cancer subtypes or where the subtype was not specified. The mean age of lung cancer diagnosis across the studies ranged from 60 to 70 years and the proportion of men ranged from 40.2% to 91.8%. The duration of follow-up also ranged from 12 months to 27.7 years.

Smoking cessation at or around the time of diagnosis was associated with a better overall survival regardless of lung cancer type. For smoking cessation at any time, compared to those who continued smoking (used as the reference group), the relative risk for non-small cell lung cancer was 0.77 (relative risk, RR = 0.77, 95% CI 0.66 – 0.90) and this reduction was broadly similar compared to those stopping strictly at or after their diagnosis or up to 12 months before the diagnosis. For small cell lung cancer, overall survival was also broadly similar (RR = 0.75, 95% CI 0.57 – 0.99). Even in studies where the cancer subtype was not specified, there were survival benefits among quitters (RR = 0.81, 95% CI 0.68 – 0.96).

The authors calculated an overall benefit for those who undertook smoking cessation at or around the time of their lung cancer diagnosis, finding that such individuals had a 29% improvement in their overall survival compared to those who continued to smoke (RR = 0.71, 95% CI 0.64 – 80).

The authors concluded that advice to quit smoking at or around the time of a lung cancer diagnosis, should arguably become a non-optional part of the management of these patients.

Citation

Caini S et al. Quitting smoking at or around diagnosis improves the overall survival of lung cancer patients: a systematic review and meta-analysis J Thorac Oncol 2022

Single low-dose CT scan helps reduce lung cancer mortality

20th September 2021

Compared to usual care, the use of a single low-dose CT scan in patients who smoke appears to reduce their risk of lung cancer mortality.

According to Cancer Research UK, there are around 47,800 new lung cancer cases each year and approximately 35,100 deaths, which equates to 96 deaths every day. Furthermore, Cancer Research UK estimates that 79% of lung cancer cases in the UK are preventable with 72% caused by smoking. With such a high incidence of not only cases, but more importantly, preventable cases, there is an urgent need for effective screening methods, especially among individuals who are deemed at high risk such as smokers. In a 1999 study, a low computed-tomography (CT scan) was shown to greatly improve the likelihood of detecting small, non-calcified nodules and hence lung cancer, at an earlier and hence more curable stage. Moreover, subsequent studies have also demonstrated a reduction in lung cancer mortality among those undergoing a low dose CT scan.

With the value of CT screening already firmly established, a UK-based team have published their own findings of a trial comparing the effect of a low dose CT scan compared to usual care, in high-risk patients. The UK lung cancer screening (UKLS) trial, randomised patients to low dose CT screening or usual care, i.e., with no CT scan and was undertaken at two thoracic hospitals in the UK. Eligible patients, aged 50 to 75 years, were those deemed to be at a high risk of developing lung cancer over the next 5 years defined by a risk score of at least 4.5% based on the Liverpool Lung Project risk model (LLPv2). This model includes several possible risk factors such as gender, age, smoking status, smoking duration, family history of lung cancer. Included patients were then randomised to the intervention group (CT scan) or usual care although given the nature of the intervention, blinding was not possible. The primary outcome was mortality due to lung cancer, defined as a death during the follow-up period where lung cancer was listed as an underlying cause. In an effort to provide further evidence, the researchers also undertook a meta-analysis of other recent trials and included their own data, to get a more robust estimate of the benefits of CT scanning.

Findings
A total of 1987 and 1981 individuals were randomised to the CT scan and control arm respectively and followed for a median of 7.3 years. The median age at consent was 68 years (25% female) and among the CT scan group, 38% were current smokers, of whom, 93% had smoked for more than 20 years. During the follow-up period, 76 lung cancers were detected, 30 in the CT scan arm and 46 in the control arm although this difference was not significant (relative risk, RR = 0.65, 96% CI 0.41 – 1.02, p = 0.062). Furthermore, there were no significant differences between the sexes. In addition, there were 512 deaths from any cause and again there was no significant difference between the groups (p = 0.315).

When these results were added to a meta-analysis of 9 randomised, controlled trials, low dose CT scan screening was associated with a 16% relative reduction in lung cancer mortality compared with no screening (RR = 0.84, 95% CI 0.76 – 0.92).
The authors concluded that while their trial had not demonstrated a statistically significant reduction in lung cancer mortality, when their data was combined with other studies, the pooled estimate was significant and provided further support for lung cancer screening via a low dose CT scan.

Citation
Field JK et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Regional health Europe 2021