The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on ...the best course of action when noncalcified pulmonary nodules are detected by CT.
A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more.
In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval CI, 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up.
Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.)
We investigated whether presence and characteristics of lung nodules in the general population using low-dose computed tomography (LDCT) varied by season. Imaging in Lifelines (ImaLife) study ...participants who underwent chest LDCT-scanning between October 2018 and October 2019 were included in this sub-study. Hay fever season (summer) was defined as 1st April to 30th September and Influenza season (winter) as 1st October to 31st March. All lung nodules with volume of ≥ 30 mm
(approximately 3 mm in diameter) were registered. In total, 2496 lung nodules were found in 1312 (38%) of the 3456 included participants (nodules per participant ranging from 1 to 21, median 1). In summer, 711 (54%) participants had 1 or more lung nodule(s) compared to 601 (46%) participants in winter (p = 0.002). Of the spherical, perifissural and left-upper-lobe nodules, relatively more were detected in winter, whereas of the polygonal-, irregular-shaped and centrally-calcified nodules, relatively more were detected in summer. Various seasonal diseases with inflammation as underlying pathophysiology may influence presence and characteristics of lung nodules. Further investigation into underlying pathophysiology using short-term LDCT follow-up could help optimize the management strategy for CT-detected lung nodules in clinical practice.
We studied 2240 indeterminate solid nodules (volume 50-500mm
) to determine the correlation of diameter and semi-automated volume measurements for pulmonary nodule size estimation. Intra-nodular ...diameter variation, defined as maximum minus minimum diameter through the nodule's center, varied by 2.8 mm (median, IQR:2.2-3.7 mm), so above the 1.5 mm cutoff for nodule growth used in Lung CT Screening Reporting and Data System (Lung-RADS). Using mean or maximum axial diameter to assess nodule volume led to a substantial mean overestimation of nodule volume of 47.2% and 85.1%, respectively, compared to semi-automated volume. Thus, size of indeterminate nodules is poorly represented by diameter.
Pre-results, ISRCTN63545820.
To evaluate the characteristics and work-up of small to intermediate-sized pulmonary nodules in a Chinese dedicated cancer hospital.
Patients with pulmonary nodules 4-25 mm in diameter detected
...computed tomography (CT) in 2013 were consecutively included. The analysis was restricted to patients with a histological nodule diagnosis or a 2-year follow-up period without nodule growth confirming benign disease. Patient information was collected from hospital records.
Among the 314 nodules examined in 299 patients, 212 (67.5%) nodules in 206 (68.9%) patients were malignant. Compared to benign nodules, malignant nodules were larger (18.0 mm
12.5 mm,
0.001), more often partly solid (16.0%
4.7%,
0.001) and more often spiculated (72.2%
41.2%,
0.001), with higher density in contrast-enhanced CT (67.0 HU
. 57.5 HU,
= 0.015). Final diagnosis was based on surgery in 232 out of 314 (73.9%) nodules, 166 of which were identified as malignant 30 (18.1%) stage III or IV and 66 as benign. In 36 nodules (11.5%), diagnosis was confirmed by biopsy and the remainder verified based on stability of nodule size at follow-up imaging (
= 46, 14.6%). Among 65 nodules subjected to gene (EGFR) mutation analyses, 28 (43.1%) cases (EGFR19
= 13; EGFR21
= 15) were identified as EGFR mutant and 37 (56.9%) as EGFR wild-type. Prior to surgery, the majority of patients
= 194 (83.6%) received a contrast-enhanced CT scan for staging of both malignant
= 140 (84.3%) and benign
= 54 (81.8%) nodules. Usage of positron emission tomography (PET)-CT was relatively uncommon
= 38 (16.4%).
CT-derived nodule assessment assists in diagnosis of small to intermediate- sized malignant pulmonary nodules. Currently, contrast-enhanced CT is commonly used as the sole diagnostic confirmation technique for pre-surgical staging, often resulting in surgery for late-stage disease and unnecessary surgery in cases of benign nodules.
Understanding cancer heterogeneity, its temporal evolution over time, and the outcomes of guided treatment depend on accurate data collection in a context of routine clinical care. We have developed ...a hospital-based data-biobank for oncology, entitled OncoLifeS (Oncological Life Study: Living well as a cancer survivor), that links routine clinical data with preserved biological specimens and quality of life assessments. The aim of this study is to describe the organization and development of a data-biobank for cancer research.
We have enrolled 3704 patients aged ≥ 18 years diagnosed with cancer, of which 45 with hereditary breast-ovarian cancer (70% participation rate) as of October 24th, 2019. The average age is 63.6 ± 14.2 years and 1892 (51.1%) are female. The following data are collected: clinical and treatment details, comorbidities, lifestyle, radiological and pathological findings, and long-term outcomes. We also collect and store various biomaterials of patients as well as information from quality of life assessments.
Embedding a data-biobank in clinical care can ensure the collection of high-quality data. Moreover, the inclusion of longitudinal quality of life data allows us to incorporate patients' perspectives and inclusion of imaging data provides an opportunity for analyzing raw imaging data using artificial intelligence (AI) methods, thus adding new dimensions to the collected data.
The relationship between smoking, airflow limitation, and lung cancer occurrence is unclear. This study aims to evaluate the relationship between airflow limitation and lung cancer, and the effect ...modification by smoking status.
We included participants with spirometry data from Lifelines, a population-based cohort study from the Northern Netherlands. Airflow limitation was defined as FEV1/FVC ratio < 0.7. The presence of pathology-confirmed primary lung cancer during a median follow-up of 9.5 years was collected. The Cox regression model was used and hazard ratios (HR) with 95% confidence interval (95% CI) were reported. Adjusted confounders included age, sex, educational level, smoking, passive smoking, asthma status and asbestos exposure. The effect modification by smoking status was investigated by estimating the relative excess risk due to interaction (RERI) and the ratio of HRs with 95% CI.
Out of 98,630 participants, 14,200 (14.4%) had airflow limitation. In participants with and without airflow limitation, lung cancer incidence was 0.8% and 0.2%, respectively. The adjusted HR between airflow limitation and lung cancer risk was 1.7 (1.4-2.3). The association between airflow limitation and lung cancer differed by smoking status former smokers: 2.1 (1.4-3.2), current smokers: 2.2 (1.5-3.2) and never smokers 0.9 (0.4-2.1). The RERI and ratio of HRs was 2.1 (0.7-3.4) and 2.5 (1.0-6.5) for former smokers, and 4.6 (95% CI, 1.8-7.4) and 2.5 (95% CI, 1.0-6.3) for current smokers, respectively.
Airflow limitation increases lung cancer risk and this association is modified by smoking status.
Ever smokers with airflow limitation are an important target group for the prevention of lung cancer.
Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to ...treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which Rodentibacter was specifically absent from ABX-treated hamsters, indicating this pathobiont may play a role in promoting disease progression. The results provide experimental support for antibiotic prophylaxis against secondary bacterial infections as an adjunct therapy in human VL patients.
To develop a machine learning-derived radiomics approach to simultaneously discriminate epidermal growth factor receptor (
), Kirsten rat sarcoma viral oncogene (
), Erb-B2 receptor tyrosine kinase 2 ...(
), and tumor protein 53 (
) genetic mutations in patients with non-small cell lung cancer (NSCLC).
This study included consecutive patients from April 2018 to June 2020 who had histologically confirmed NSCLC, and underwent pre-surgical contrast-enhanced CT and post-surgical next-generation sequencing (NGS) tests to determine the presence of
,
,
, and
mutations. A dedicated radiomics analysis package extracted 1672 radiomic features in three dimensions. Discriminative models were established using the least absolute shrinkage and selection operator to determine the presence of
,
,
, and
mutations, based on radiomic features and relevant clinical factors.
In 134 patients (63.6 ± 8.9 years), the 20 most relevant radiomic features (13 for
) to mutations were selected to construct models. The areas under the curve (AUCs) of the combined model (radiomic features and relevant clinical factors) for discriminating
and
mutations were 0.78 (95% CI: 0.70-0.86), 0.81 (0.69-0.93), 0.87 (0.78-0.95), and 0.84 (0.78-0.91), respectively. In particular, the specificity to exclude
mutations was 0.96 (0.87-0.99). The sensitivity to determine
,
, and
mutations ranged from 0.82 (0.69-90) to 0.92 (0.62-0.99).
Machine learning-derived 3D radiomics can simultaneously discriminate the presence of
,
,
, and
mutations in patients with NSCLC. This noninvasive and low-cost approach may be helpful in screening patients before invasive sampling and NGS testing.
Objectives
Multiple lung cancer screening studies reported the performance of Lung CT Screening Reporting and Data System (Lung-RADS), but none systematically evaluated its performance across ...different populations. This systematic review and meta-analysis aimed to evaluate the performance of Lung-RADS (versions 1.0 and 1.1) for detecting lung cancer in different populations.
Methods
We performed literature searches in PubMed, Web of Science, Cochrane Library, and Embase databases on October 21, 2022, for studies that evaluated the accuracy of Lung-RADS in lung cancer screening. A bivariate random-effects model was used to estimate pooled sensitivity and specificity, and heterogeneity was explored in stratified and meta-regression analyses.
Results
A total of 31 studies with 104,224 participants were included. For version 1.0 (27 studies, 95,413 individuals), pooled sensitivity was 0.96 (95% confidence interval CI: 0.90–0.99) and pooled specificity was 0.90 (95% CI: 0.87–0.92). Studies in high-risk populations showed higher sensitivity (0.98 95% CI: 0.92–0.99 vs. 0.84 95% CI: 0.50–0.96) and lower specificity (0.87 95% CI: 0.85–0.88 vs. 0.95 (95% CI: 0.92–0.97) than studies in general populations. Non-Asian studies tended toward higher sensitivity (0.97 95% CI: 0.91–0.99 vs. 0.91 95% CI: 0.67–0.98) and lower specificity (0.88 95% CI: 0.85–0.90 vs. 0.93 95% CI: 0.88–0.96) than Asian studies. For version 1.1 (4 studies, 8811 individuals), pooled sensitivity was 0.91 (95% CI: 0.83–0.96) and specificity was 0.81 (95% CI: 0.67–0.90).
Conclusion
Among studies using Lung-RADS version 1.0, considerable heterogeneity in sensitivity and specificity was noted, explained by population type (high risk vs. general), population area (Asia vs. non-Asia), and cancer prevalence.
Clinical relevance statement
Meta-regression of lung cancer screening studies using Lung-RADS version 1.0 showed considerable heterogeneity in sensitivity and specificity, explained by the different target populations, including high-risk versus general populations, Asian versus non-Asian populations, and populations with different lung cancer prevalence.
Key Points
•
High-risk population studies showed higher sensitivity and lower specificity compared with studies performed in general populations by using Lung-RADS version 1.0.
•
In non-Asian studies, the diagnostic performance of Lung-RADS version 1.0 tended to be better than in Asian studies.
•
There are limited studies on the performance of Lung-RADS version 1.1, and evidence is lacking for Asian populations.
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