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Press Releases

Take a look at a selection of our recent media coverage:

Avelumab and radium-223 to be studied in stage 4 breast cancer

24th September 2021

Although both avelumab and radium-223 are approved for use in oncology, the combination will be tested for incurable stage 4 breast cancer.

A new clinical trial could bring hope to thousands of UK women living with Stage 4 breast cancer, which has only a 25% survival rate after 5 years. The trial, which is being funded by the Breast Cancer Now Catalyst Programme, aims to explore the combined effect of radium-223 and avelumab in patients with metastatic breast cancer. The monoclonal antibody avelumab, is already licensed for the treatment of metastatic Merkel cell carcinoma and advanced renal cell carcinoma. Its mode of action involves blockage of the protein, PD-L1 found on tumour cells. The PD-L1 protein decreases the immune system’s ability to kill cancer cells, hence blockage enables the immune system to recognise and destroy cancer cells. There is already some data that avelumab has an acceptable safety profile and clinical activity in a subset of patients with metastatic breast cancer.

Radium-223, brand name, Xofigo, is radiopharmaceutical and which is also licensed for use as either mono-therapy or in combination with luteinising hormone releasing hormone (LHRH) for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases and no known visceral metastases. In patients with stage 4 breast cancer, the most common distal site for spreading is bone and which occurs in up to 51% of cases. Radium-223 selectively binds to areas of increased bone turnover in bone metastases and emits high-energy alpha particles which have a short range which limits damage to adjacent areas of tissue. Although radium-223 has not been used in metastatic breast cancer, a second on-going trial is examining feasibility and safety of combining radium-223 given on a 6-weekly schedule, in combination with orally administered capecitabine in breast cancer patients with bone metastases.

The avelumab and radium-223 trial is led by Professor Janet Brown at the University of Sheffield, and run by the Clinical Trials Research Unit at the University of Leeds. If successful, this combination of drugs could provide a new way to treat secondary breast cancer.

Durvalumab and chemotherapy effective for extensive-stage small cell lung cancer

Durvalumab and chemotherapy in extensive stage small cell lung cancer showed an improved overall survival compared to chemotherapy alone.

Small cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine malignancy with a high metastatic potential and is associated with poor clinical outcomes.  Patients with extensive-stage small cell lung cancer (ES-SCLC) are normally treated with combination chemotherapy which includes carboplatin or cisplatin plus etoposide. In 2019 the CASPIAN study was published which compared combination chemotherapy, consisting of etoposide + cisplatin/carboplatin (EP), in treatment-naive patients with ES-SCLC with the addition of either durvalumab or tremelimumab. The results showed that addition of durvalumab (D + EP) led to a 27% reduction in the risk of death (Hazard ratio, HR = 0.73, 95% CI 0.59-0.91; p=0.0047) compared to chemotherapy alone. In a 2020 study update, the manufacturer, AstraZeneca, announced that after two years of follow-up, durvalumab (brand name Imfinzi), maintained a 25% reduction in the risk of death versus chemotherapy alone (HR of 0.75; 95% CI 0.62, 0.91; nominal p=0.0032). 

The latest results for the CASPIAN trial were presented at the ESMO 2021 conference. These show that after a median follow-up of 39.4 months, durvalumab and EP continued to maintain a 29% survival benefit (HR = 0.71, 95% CI 0.60–0.86; nominal p=0.0003) over chemotherapy. In terms of survival, 22.9% vs 13.9% of patients given durvalumab plus chemotherapy were alive at 24 months and 17.6% vs 5.8% of patients were alive at 36 months with D + EP vs EP.

The incidence of serious adverse events was broadly similar at 32.5%, and 36.5% for durvalumab and EP and EP alone respectively. Adverse events leading to death occurred 5.3%, and 6.0% (D +EP vs ES alone).

Given the overall survival benefit, the authors of the abstract concluded that their data further established D + EP as standard of care for the first-line treatment of ES-SCLC.

Source: AstraZeneca release 2021

Artificial intelligence appears to be less accurate than radiologists in breast cancer screening

23rd September 2021

Breast cancer screening using artificial intelligence systems has been found, in the majority of cases, to be less accurate than a radiologist.

Globally, in 2020, there were an estimated 2.3 million women diagnosed with breast cancer leading to 685,000 deaths. Fortunately, improvements in survival over recent decades have been attributed to population-based breast cancer screening with mammography. In fact, a recent UK study suggested that screening reduces cancer mortality by 38% among women screened at least once.

The use of artificial intelligence (AI) systems for image recognition in breast cancer screening could lead to improvements in the detection of cases, either as a standalone system or as an aid to radiologists. Indeed, there is some evidence to support the value of AI with one retrospective analysis of an AI screening algorithm concluding that it showed better diagnostic performance than a radiologist. Nevertheless, in a 2019 review, it was concluded that while AI systems have good accuracy for breast cancer detection, methodological concerns and evidence gaps exist that limit translation into clinical breast cancer screening settings.

In light of these concerns, a team from the Division of Health Sciences, University of Warwick, UK, were commissioned by the UK National Screening Committee to undertake a systematic review to determine whether there was sufficient evidence to support the introduction of AI for mammographic image analysis in breast screening. They conducted literature searches up to May 2021 and included studies that reported the test accuracy of AI algorithms either alone or in combination with radiologists, to detect breast cancer in digital mammograms in screening practice or in test sets. The team included cancer confirmed by histological analysis of biopsy samples in cases where women were referred for further tests after screening as the reference standard or from symptomatic presentation during follow-up.

Findings
The review identified a total of 12 studies including 131,822 women undergoing breast cancer screening. In studies with a standalone AI system, the algorithm calculated a cancer risk score, categorising women at either high (recall) or low (no recall) risk. When used to assist the radiologist, the AI system simply provided a level of suspicion. In two large retrospective studies including 76,813 women, that compared the AI system with the clinical decisions of a radiologist, 96% of systems were less accurate than a single radiologist and all were less accurate than a double read.
Overall, the authors reported considerably heterogeneity in study methodology, some of which resulted in high concerns over the risk of bias and applicability. In their study, they commented that “evidence is insufficient on the accuracy or clinical effect of introducing AI to examine mammograms anywhere on the screening pathway”.

In the conclusion, the authors noted how AI systems for breast cancer screening are a long way from having the quality and quantity required for implementation into clinical practice.

Citation
Freeman K et al. Use of artificial intelligence for image analysis in breast cancer screening programmes: systematic review of test accuracy. BMJ 2021

Less than half of radiologists successfully complete on-line self-assessment

21st September 2021

Using a mammography on-line self-assessment, less than half of Italian radiologists were able to successfully completed the test.

Detection of breast cancer requires that mammography scans are interpreted correctly and thus guidelines on screening require that robust quality control and quality assurance are in place. Although an assessment of performance against standards can be achieved through audits, such audits offer little insight of the diagnostic skills of individual radiologists. The use of on-line self-assessment, using pre-diagnosed mammograms, offers a means of identifying any knowledge gaps and could serve as an important educational tool.

An on-line self-assessment tool was adopted by the Italian Society of Medical Radiology in 2018 as part of a national on-line self-assessment program for interpretation of mammograms and the results have published. The test set was a collection of 24 pathology-confirmed cancers combined with 108 mammograms which were reported on as negative after double reading. All cases were acquired with full-field digital mammography and came from women aged 50 – 69 years, who represent those at average risk of breast cancer. For the assessment, the society determined a pass threshold for sensitivity of 62% (amounting to at least 15/24 cancers correctly identified) and 86% specificity (93/108 negative mammograms correctly identified). The on-line self-assessment was posted on a dedicated website and upon registration, radiologists provided information on demographics such as age, gender, place of work (public or private sector), years of breast imaging experience and a qualitative self-judgement of mammography interpretative skills as “beginner”, “average” and “expert”. As with usual mammography practice, the radiologists were required to submit a dichotomous diagnosis (i.e., positive/negative) for every case. In addition to reporting on the radiologist’s success in the test, the authors employed regression analysis and odds ratios to identify the most important predictor variables for diagnostic accuracy.

Findings
A total of 685 radiologists registered for the on-line self-assessment and 49.9% (342) with a mean age of 46 years (69% female), completed test. Among those completing, two-thirds (64%) self-judged their interpretative skills as “average” and respondents had a median of 8 years breast imaging experience although 38.3% reporting having more than 10 years’ experience. Participants reported a median number of 1501 mammographic interpretations per year and the majority (68.7%) worked in the public rather than private sector.

When examining the proportion who successfully completed the assessment, only 28.7% of radiologists (98/342) passed on their first attempt. After an initial failure, 138 of the remaining 244 radiologists, re-took the test of whom, only 35.5% (49/138) passed. In fact, the authors reported that overall, only 44.2% (151/342) of radiologists who completed the on-line self-assessment were successful.
Using regression analysis, a significant association for diagnostic accuracy was found only for the assessment of > 3,000 mammograms per year compared to < 1,000 (Odds ratio, OR = 3.88, 95% CI 1.07 – 14.14, p = 0.04) and working the in public rather than private sector (OR = 1.65). Other variables such as age, self-judged interpretative skills and years of breast imaging experience had no significant effect.
The authors concluded that their study suggested that breast imaging experience does not guarantee diagnostic accuracy in screening reading. They also noted that their on-line self-assessment test could be included as a criterion for the accreditation process of breast units.

Citation
Brancato B et al. Mammography self?evaluation online test for screening readers: an Italian Society of Medical Radiology (SIRM) initiative. Eur Radiol 2021

Low-density lipoprotein reduction from daily intake of walnuts

A study has found that elderly patients who ate a handful of walnuts every day for 2 years saw reductions in low-density lipoprotein levels.

Regular intake of nuts has been associated with a 15% lower risk of cardiovascular disease and a 23% lower risk of cardiovascular mortality. This reduction in risk is probably due to a reduction in low-density cholesterol (LDL-C) levels with one pooled analysis of 25 intervention trials finding that a mean daily intake of 67g of nuts produced a 7.4% mean reduction in LDL-C levels. However, none of the 25 trials lasted longer than 8 weeks and have not examined the effect of nuts on different LDL sub-fractions. In trying to establish the effect of both daily nut consumption and any differences in the effect on low-density lipoprotein levels, a team from the Lipid Clinic, Endocrinology and Nutrition Services, Villarroel, Barcelona, Spain, decided to explore these effects in a randomised trial. The team established the Walnuts and Healthy Aging (WAHA) trial which ran from 2012 to 2014 and was designed to examine the impact of bioactive compounds, such as n-3 fatty acids (found in walnuts) on both cognitive function and retinal health. Free-living participants were randomised to receive 30 – 60g/day of walnuts, which were delivered to the intervention group individuals, or to abstain from the nuts for the two years of the trial. One of the secondary outcomes of the original trial was changes in lipoprotein levels. Together with fasting glucose, lipoprotein levels were were measured at baseline at after 2 years. In addition, given that those eating walnuts were consuming more fat and thus likely to experience weight gain, this was also measured and compared with the baseline reading.

Findings
There were 636 participants with a mean age of 69 years (67% female) who completed the two-year trial. The mean baseline LDL-C and triglyceride levels were 117 and 105 mg/dL respectively. Among those taking walnuts, mean total cholesterol levels decreased by 4.4%
(-8.5 mg/dL, 95% CI -11.2 to -5.4), LDL-C by 3.6% (-4.3, 95% CI -6.6 to -1.6) and intermediate-density lipoprotein cholesterol by 16.8% (-1.3, 95% CI -1.50 to -1.0). Interestingly, levels of both triglycerides and high-density lipoprotein levels were unchanged. Weight changes in the walnut group were negligible at 0.06kg (95% CI -0.32 to 0.44). Furthermore, LDL-C reductions were higher for men than women (7.9% vs 2.6%, men vs women). In addition, there were also reductions in total LDL particles and small LDL particle number by 4.3% and 6.1% respectively.
The authors suggest that the reduction is LDL-C cholesterol at 4.3 mg/dL was modest and concluded that daily walnut intake may be useful way to improve cardiovascular risk.

Citation
Rajaram S et al. Effects of Walnut Consumption for 2 Years on Lipoprotein Subclasses Among Healthy Elders. Findings From the WAHA Randomized Controlled Trial. Circulation 2021.

Similar factors associated with COVID-19 severity in children and adults

A US study has found that as with adults, the same clinical factors affect COVID-19 severity and hospitalisation in children and adolescents.

The available evidence clearly shows that infection with COVID-19 is disproportionately higher in adults compared with children. Nevertheless, emerging data suggests that in children infection with COVID-19 can induce multisystem inflammatory syndrome and lead to serious illness. While the pandemic has revealed how several clinical factors such as older age, various co-morbidities and ethnicity, are all associated with a higher level of COVID-19 severity, much less is known about which factors lead to more severe disease in children.

This lack of information prompted a group of US researchers from the Division of Hospital Medicine, Monroe Carell Jr, Children’s Hospital, Vanderbilt, Nashville, Tennessee, US, to undertake a retrospective cohort study across 45 US children’s hospitals to assess factors associated with COVID-19 severity in paediatric patients. The researchers included patients as young as 30 days old to 18 years of age, discharged from either an emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19. The researcher collected demographic data and information on the presence of any co-morbidities, particularly those which appeared to result in a worse prognosis among adults. The outcome of interest was COVID-19 severity which was categorised as mild (i.e., ED discharge), moderate (in-patient admission) and severe (intensive care (ICU) admission) and very severe (ICU admission with mechanical ventilation, shock or death). The results were analysed using regression analysis and presented as odds ratios adjusted for various factors including ethnicity and co-morbidities.

Findings
The study included 19,976 ED encounters of children with a median age of 6 years (51.2% male) with the most common ethnicities being Hispanic (48.8%) and non-Hispanic White (21.1%). In the majority of cases (79.9%) COVID-19 severity was mild (79.7%) and these individuals were discharged from the ED. However, among the 4063 (20.3%) patients who were hospitalised, the majority had moderate COVID-19 severity (79.3%) with 11.3% classed as severe and 9.4% as very severe. When compared with those who were discharged from the ED, the clinical factors associated with an increased odds of hospitalisation included obesity/type 2 diabetes (adjusted Odds ratio, aOR = 10.4, 95% CI 8.90 – 13.3), asthma (aOR = 1.40, 95% CI 1.3 – 1.60), cardiovascular disease (aOR = 5.0), an immunocompromised condition (aOR = 5.9) and pulmonary disease (aOR = 3.2). Only Black ethnicity impacted on the risk of hospitalisation compared to those of White ethnicity, (aOR = 1.52, 95% CI 1.20 – 1.93). With respect to age, compared to children aged 0 – 4 years, the risk of hospitalisation was lower among those aged 5 – 11 years (aOR = 0.50, 95% CI 0.45 – 56) and 12 – 17 years (aOR = 0.75, 95% CI 0.69 – 0.82). However, once hospitalised, the risk of higher COVID-19 severity increased in both groups: 5 – 11 group (aOR = 2.66) and 12 – 17 years (aOR = 2.09).
The authors concluded that while older children were at a lower risk of hospitalisation with COVID-19, once hospitalised, they appeared to be a higher risk of more severe disease. In addition, as with adults, similar co-morbidities were associated with a greater risk of hospitalisation and higher COVID-19 severity once admitted.

Citation
Antoon JW et al. Factors associated with COVID-19 disease severity in US children and adolescents. J Hosp Med 2021

Medical cannabis provides only small improvement in chronic pain

A systematic review found that use of non-inhaled medical cannabis in patients with chronic pain leads to only a small improvement compared with placebo.

In a 2006 European survey of over 46,000 respondents in 15 countries, 19% reported experiencing pain which lasted for at least 6 months. Moreover, a more recent 2019 study in developing countries found a similar incidence (18%) among the general population. However, the impact of chronic pain, i.e., which persists past the normal healing time and lasts or recurs for more than 3 to 6 months, has a much wider impact upon affected individuals, reducing physical functioning, daily activities and mental health. Although opioid drugs have been used for the management of chronic pain, evidence suggests that compared with placebo, there are only small beneficial effects. Consequently, there has been increased interest in the use of alternative pain management strategies, one of which is the use of medical cannabis. In fact, its use as a therapeutic alternative has been recommended in some guidance for chronic pain, especially in cases where other treatments have been ineffective. However, the overall effectiveness of medical cannabis in chronic pain remains unclear with some organisations such as NICE in the UK, advising against the use of cannabis-based medicinal products to manage chronic pain in adults unless as part of a clinical trial.

With uncertainty over the effectiveness of medical cannabis in chronic pain, Canadian researchers led by a team from the Department of Anesthesia, McMaster University, Ontario, Canada, performed a systematic review and meta-analysis to determine the benefits and harms of medical cannabis in patients with chronic pain, including cancer pain. They included randomised controlled trials that enrolled at least 20 patients with chronic pain (defined as lasting longer than 3 months) and who were assigned to any form of medical cannabis and which was compared to placebo with a follow-up period of at least one month. As well as the impact on pain, the team also captured data on physical, emotional and social functioning and sleep quality. They assessment the benefits in terms of change scores from baseline as opposed to end of study results and determined whether use of cannabis achieved the minimally important difference (MID). This represents the smallest amount of improvement in a treatment outcome that patients recognise as important. For example, using a 10 cm visual analogue scale for pain, the MID is approximately 1 cm. The researchers modelled the risk difference (RD) of achieving at least the MID.

Findings
A total of 32 trials with 5174 adults in which 29 compared medical cannabis with placebo were included in the analysis. In terms of pain relief, there was moderate certainty evidence from 27 trials that medical cannabis compared to placebo, resulted in a small increase in the proportion of patients experiencing pain relief at or above the MID. This difference was modelled as 10 % (95% CI 5% to 15%). Data from 10 trials suggested a 7% increase in the proportion of patient experiencing at least a 30% reduction in pain with medical cannabis compared to placebo. Similarly, there was a 4% modelled difference in physical functioning and a 6% modelled risk difference for an improvement in sleep quality. However, there was no apparent improvement in emotional or social functioning. With respect to adverse effects, it appeared that medical cannabis gave rise to a 2% risk of transient cognitive impairment, impaired attention (3%) and nausea (5%).

The authors concluded that there was moderate to high certainty evidence of a small to very small increase in the proportion if people with chronic pain who experience an important improvement in their pain. Their results have been summarised in an accompanying rapid recommendation.

Citation
Wang L et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ 2021

Lung ultrasound severity index score predicts COVID-19 diagnosis

20th September 2021

A lung ultrasound severity index tool has been shown to be able to identify those with COVID-19 and predict in-hospital mortality.

Although a formal diagnosis of COVID-19 is based on a positive PCR test, it can take up to 24 hours before the result is available. Given that COVID-19 is a respiratory infection, clinicians have often turned to chest imaging with lung ultrasound, X-rays and CT scans, to diagnose the infection prior to confirmation from a PCR test. In fact, a Cochrane review has concluded that the use of a lung ultrasound correctly diagnoses COVID-19 in 86.4% of infected patients.

With the potential value of lung ultrasound as a diagnostic aid in COVID-19, an Italian team from the Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy, undertook a prospective, observational study to further examine the value of the imaging modality in those with suspected COVID-19. Patients were those consecutively admitted to the emergency department of a single hospital with suspected COVID-19. Each underwent a standard lung ultrasound examination which included 12 thoracic areas. The team then calculated several different measures with a view to determining whether any of these could be used prognostically for COVID-19. The scores for each thoracic areas were added to calculate a regional lung ultrasound severity score (rLUSS) and a lung ultrasound severity score (LUSS) was calculated by summing all rLUSS values. The number of different ultrasound patterns found in each area defined the regional lung ultrasound heterogeneity score (rLUHS). A regional lung ultrasound severity index (rLUSI) was then calculated as rLUSS/rLUHS for each area. Finally, the team computed a lung ultrasound severity index (LUSI), which was the sum of all the rLUSI scores. The team were interested in whether LUSI, rLUSS or LUHS. The outcomes of interest were a diagnosis of COVID-19 pneumonia and in-hospital mortality and the area under the receiver operating curves (AUROC) analysis was used to determine the relationship between LUSS, LUHS, LUSI and the severity of pneumonia.

Findings
The study included 159 patients with a mean age of 64.6 years (66% male) of whom, 49% had respiratory failure upon admission. For each of the three lung ultrasound measures (i.e., LUSS, LUHS and LUSI), in relation to the differentiation of COVID-19 positive and negative cases, LUSI offered the greatest sensitivity and specificity with an AUROC of 0.72 (95% CI 0.64 – 0.78), giving a sensitivity of 63% and a specificity of 75%. With respect to overall in-hospital mortality, again LUSI scores provided the best AUROC, at 0.81 (95% CI 0.73 – 0.86) providing a sensitivity of 90.9% and a specificity of 65.6%. Finally, when considering only COVID-19 patients, LUSI also gave the highest AUROC, 0.76 (95% CI 0.66 – 0.84) with a sensitivity of 63.1% and a specificity of 90%.

The authors concluded that their newly developed lung ultrasound severity index provided the highest accuracy with respect to COVID-19 diagnosis and prognosis. They also added that a further advantage was how the lung ultrasound could be performed in under 10 minutes, allowing LUSI scores to quickly identify patients at a higher risk of both COVID-19 and mortality and called for future studies to understand LUSI’s role for different clinical goals such as monitoring of treatment or progression.

Citation
Spampinato MD et al. Lung Ultrasound Severity Index: Development and Usefulness in Patients with Suspected SARS-Cov-2 Pneumonia. A Prospective Study. Ultrasound Med Biol 2021

Second scan prior to radiotherapy identifies need for treatment changes

Among patients with squamous cell carcinomas, a second scan prior to radiotherapy prompted treatment changes in just over half of cases.

A squamous cell carcinoma on the head or neck is the sixth most common cancer globally, with around 890,000 new cases and 450,000 deaths in 2018. The main form of treatment is curative radiotherapy and in patients with locoregionally advanced cancers, prior scanning with fluorodeoxyglucose positron emission tomography and computed tomography (PET-CT) has been shown to have good diagnostic performance for the detection of regional nodal metastasis. However, where there is a delay between radiotherapy and the initial PET-CT scan, does this impact on radiotherapy planning and might it be necessary to perform a second scan prior to radiotherapy? This was the question posed by researchers from the Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland. The team performed a retrospective analysis of patients with advanced head or neck squamous cell carcinoma and who had received two PET-CT scans prior to radiotherapy, to determine whether the second scan led to any modifications to radiotherapy treatment. The team looked for changes in the primary tumour, lymphatic spread and the presence of distant metastases between the two scans. They categorised any changes as minor if there were modifications to the RT plans such as dose changes and major where treatment moved from curative to palliative or the addition of induction chemotherapy, a switch to surgery or any additional diagnostic work-up that led to postponement or cancellation of treatment.

Findings
There were 32 newly diagnosed patients with locoregionally advanced squamous cell cancer with a median age of 64 years (34% female). The median interval between the initial scan for staging assessment and the second scan was 42.5 days. Just over half (53%) of patients had a grade 2 and 41% a grade 3 tumour. Fortunately, a major treatment change occurred in only 1 patient although nodal upstaging occurred in 10% (3/29) of patients. Minor treatment changes were required in 52% (16/31) of patients with new lymph node metastases detected in all 16 patients and in 6 cases, there was evidence of progression of the primary tumour size.

In discussing their findings, the authors noted that despite an initial PET-CT scan to assess tumour staging, a second scan identified the need for minor changes in just over half of all patients. Based on these findings, they called for the potential benefits of a second scan to be further investigated and validated. They also noted that the practice of undertaking a second scan of patients where the delay was more than four weeks has become the established practice at their hospital.

Citation
Elicin O et al. Impact of pre-treatment second look 18FDG-PET/CT on stage and treatment changes in head and neck cancer. Clin Trans Radiat Oncol 2021

Single low-dose CT scan helps reduce lung cancer mortality

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