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"MacEachern, Paul"
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USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study
2022
Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria.
In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55–80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete.
Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enrolled on the basis of meeting USPSTF2013 criteria or the PLCOm2012 risk threshold of at least 1·51% at 6 years. The same number of individuals was selected for the PLCOm2012 model as for the USPSTF2013 criteria (4540 [78%] of 5819). After a mean follow-up of 2·3 years (SD 1·0), 135 lung cancers occurred in 4540 USPSTF2013-positive participants and 162 in 4540 participants included in the PLCOm2012 of at least 1·70% at 6 years group (cancer sensitivity difference 15·8%, 95% CI 10·7–22·1%; absolute odds ratio 4·00, 95% CI 1·89–9·44; p<0·0001). Compared to USPSTF2013-positive individuals, PLCOm2012-selected participants were older (mean age 65·7 years [SD 5·9] vs 63·3 years [5·7]; p<0·0001), had more comorbidities (median 2 [IQR 1–3] vs 1 [1–2]; p<0·0001), and shorter life expectancy (13·9 years [95% CI 12·8–14·9] vs 14·8 [13·6–16·0] years). Model-based difference in cumulative life expectancies for those diagnosed with lung cancer were higher in those who had PLCOm2012 risk of at least 1·70% at 6 years than individuals who were USPSTF2013-positive (2248·6 years [95% CI 2089·6–2425·9] vs 2000·7 years [1841·2–2160·3]; difference 247·9 years, p=0·015).
PLCOm2012 appears to be more efficient than the USPSTF2013 criteria for selecting individuals to enrol into lung cancer screening programmes and should be used for identifying high-risk individuals who benefit from the inclusion in these programmes.
Terry Fox Research Institute, The UBC-VGH Hospital Foundation and the BC Cancer Foundation, the Alberta Cancer Foundation, the Australian National Health and Medical Research Council, Cancer Research UK and a consortium of funders, and the Roy Castle Lung Cancer Foundation for the UK Lung Screen Uptake Trial.
Journal Article
Probability of Cancer in Pulmonary Nodules Detected on First Screening CT
by
Soghrati, Kam
,
Stewart, Lori
,
Bhatia, Rick
in
Biological and medical sciences
,
Clinical trials
,
Computed tomography
2013
Using data from two large data sets of lung-cancer screening by CT, the authors identified factors that increased the likelihood that a nodule was malignant, including older age, female sex, nodule location in the upper lobe, lower nodule count, and certain nodule features.
The U.S. National Lung Screening Trial showed that screening with the use of low-dose thoracic computed tomography (CT) reduces mortality from lung cancer by 20%.
1
Major clinical issues in the implementation of low-dose CT screening at the population level include the definition of a positive screening result and the appropriate management of lung nodules detected on a scan. More than 20% of participants in low-dose CT screening programs were found on their first scan to have one or more lung nodules that required further investigation.
1
–
4
The proportion of invasive diagnostic procedures ranged from 1 to 4%.
1
,
3
The risk . . .
Journal Article
Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer
by
Jankowska, Anna J.
,
Zheng, Zhendong
,
Learch, Thomas B.
in
ADP-ribosyl Cyclase 1 - physiology
,
Adult
,
Antigens
2015
Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.
Journal Article
Combined medical-interventional approaches for the management of complex fungal balls: a case series as a viable alternative in non-surgical patients
by
Thornton, Christina S.
,
Tremblay, Alain
,
MacGregor, John H.
in
Adult
,
Aged
,
Antifungal agents
2024
Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32–73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5–10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.
Plain Language Summary
The use of both medical and interventional methods to treat difficult fungal masses: A collection of cases showing efficacy for patients who can’t undergo surgery
Intracavitary pulmonary aspergilloma is a serious and potentially deadly infection with a death rate of up to 15%. It happens when certain types of fungi invade existing lung cavities. Without proper treatment, patients may experience severe complications like heavy bleeding from the lungs, weight loss, or other infections. Traditional antifungal medications often don’t work well because they can’t reach high enough concentrations in the cavities. Surgery is usually the best option, but it’s risky and not possible for many due to other health problems. Our study introduces a new way to treat aspergilloma without surgery. We’ve treated a significant number of patients using a combination of antifungal drugs and a procedure called bronchoscopic debulking. This involves removing the fungal growth using a thin tube inserted through the airways. Our research involved observing 18 patients treated this way. They were mostly middle-aged, with equal numbers of men and women. Their lung function was moderately impaired, and we followed them for an average of 3.6 years. We found that giving antifungal drugs before the debulking procedure helped reduce the size of the cavities. After treatment, almost all patients remained free of symptoms and signs of recurrence. This study highlights the importance of starting antifungal therapy before bronchoscopic debulking and offers a promising option for patients who can’t have surgery.
Journal Article
Prevalence and incidence of idiopathic subglottic stenosis in southern and central Alberta: a retrospective cohort study
by
Bosch, J. Douglas
,
MacEachern, Paul
,
Chan, Ryan K.
in
Alberta
,
Alberta - epidemiology
,
Bronchoscopy
2021
Background
Subglottic stenosis (SGS) is a reportedly rare disease that causes recurrent severe airway obstruction. Etiologies reported for SGS include idiopathic, iatrogenic, autoimmune, congenital, and traumatic, with variable ratios among different centres. From empiric observation, southern and central Alberta was hypothesized to have a disproportionate distribution of SGS driven by increased idiopathic SGS (iSGS) compared to previous literature. Identification of causative agents of iSGS will help understand and guide future management options, so this study aimed to characterize the demographics of SGS subtypes, define prevalence and incidence rates of iSGS in southern Alberta, and geographically analyze for clustering of iSGS prevalence.
Methods
SGS patients from Alberta census divisions No. 1–9 and 15 were retrospectively reviewed. Patients were subtyped according to etiology of SGS and characterized. Idiopathic SGS prevalence and incidence was assessed; prevalence was further geographically segregated by census division and forward sortation area (FSA). Significant clustering patterns were assessed for using a Global Moran’s I analysis.
Results
From 2010 to 2019 we identified 250 SGS patients, who were substantially overrepresented by idiopathic patients (80.4%) compared to autoimmune (10.0%), iatrogenic (7.6%), congenital (1.2%), and traumatic (0.8%). The total iSGS prevalence was 9.28/100,000 with a mean annual incidence rate of 0.71/100,000 per year. Significant clustering was observed (Moran’s index 0.125; z-score 2.832;
p
= 0.0046) and the highest rates of prevalence were observed in southern Alberta and in rural communities heterogeneously dispersed around Calgary FSAs.
Conclusion
In southern and central Alberta, iSGS patients were disproportionately over-represented in contrast to other subtypes with the highest prevalence in southern Alberta. There was a three-fold higher annual incidence compared to previous literature demonstrating the highest rates of disease reported worldwide. Future research aims to expand the geographical scope and to assess for demographic or environmental differences within significant clusters that may contribute to disease pathophysiology.
Level of evidence
III.
Graphical Abstract
Journal Article
Development and application of an electronic synoptic report for reporting and management of low-dose computed tomography lung cancer screening examination
2022
Background
Interpretation of Low Dose CT scans and protocol driven management of findings is a key aspect of lung cancer screening program performance. Reliable and reproducible methods are needed to communicate radiologists’ interpretation to the screening program or clinicians driving management decision.
Methods
We performed an audit of a subset of dictated reports from the PANCAN study to assess for omissions. We developed an electronic synoptic reporting tool for radiologists embedded in a clinical documentation system software. The tool was then used for reporting as part of the Alberta Lung Cancer Screening Study and McGill University Health Centre Pilot Lung Cancer Screening Program.
Results
Fifty reports were audited for completeness. At least one omission was noted in 30 (70%) of reports, with a major omission (missing lobe, size, type of nodule in report or actionable incidental finding in recommendation section of report) in 24 (48%). Details of the reporting template and functionality such as automated nodule cancer risk assessment, Lung-RADS category assignment, auto-generated narrative type report as well as personalize participant results letter is provided. A description of the system’s performance in its application in 2815 CT reports is then summarized.
Conclusions
We found that narrative type radiologist reports for lung cancer screening CT examinations frequently lacked specific discrete data elements required for management. We demonstrate the successful implementation of a radiology synoptic reporting system for use in lung cancer screening, and the use of this information to drive program management and communications.
Journal Article
Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients
by
Tremblay, Alain
,
D'Silva, Adrijana
,
Brenner, Darren
in
Aged
,
Biology and Life Sciences
,
Biomarkers, Tumor - genetics
2017
Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment.
We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed. Multi-state modeling (MSM) and a Cox PH regression model with propensity score weights adjusted for clinicopathological variables between: diagnosis and PD and PD to death.
123 stage IIIA-IV patients were identified with 104 meeting RECIST-1.1-PD criteria. This RECIST-1.1-PD criteria subset included females (64.6%), Asians (39.4%), never/non-smokers (55.8%), and exon 19 deletion carriers (44.2%). Commonest treatment beyond initial-PD was continuing TKI alone (46/104), with another 21 patients continuing TKI plus additional systemic therapy. The median OS for patients who continued TKI treatment at initial-PD was 21.1 months versus 15.6 months for patients who discontinued TKI, p = 0.006. Via MSM analysis, continuing TKI at initial-PD followed by other systemic therapy was associated with an 83% reduced death risk, adjusted HR: 0.17 (95% CI: 0.07, 0.39). In the Cox PH model, ever-smokers with an exon 19 deletion had increased risk of death after PD (adjusted HR: 3.19, 95% CI: 1.54, 6.58), as did exon 21 mutation carriers, (adjusted HR: 2.10, 95% CI: 1.10, 4.00) and females (adjusted HR: 3.19, 95% CI: 1.54, 6.58).
Subsequent systemic therapy after continuing TKI at initial-PD reduced the risk of death. Additionally, our data suggest that positive smoking history increases death risk for some EGFR mutation types and females.
Journal Article
Protocol for the Stather Canadian Outcomes Registry for Chest ProcedurEs (SCOPE)
by
Stollery, Daniel
,
Hergott, Christopher
,
Dhaliwal, Inderdeep
in
Bias
,
bronchoscopy
,
Clinical medicine
2021
IntroductionThe Stather Canadian Outcomes registry for chest ProcedurEs (SCOPE registry) is a Canadian multicentre registry of chest procedures.Methods and analysisThe SCOPE registry is designed as a multicentre prospective database of specific bronchoscopic or other pulmonary procedures. Each procedure of interest will be associated with a registry module, and data capture designed to evaluate effectiveness of procedures on relevant patient outcomes. Participating physicians will be asked to enter data for all procedures performed in a given module. The anonymised dataset will be housed in a web-based electronic secure database. Specific modules included will be based on participating physician suggestions, capacity and consensus of the steering committee and relevance of hypotheses/research potential.Ethics and disseminationThe central registry is under approval from the Conjoint Health Research Ethics Board at the University of Calgary. We aim for registry data to lead to publication of manuscripts in international medical journals as the primary mode of dissemination. Data may also be used by local investigators for personal and/or institutional quality control purposes as well as to inform health policies. Data requests from non-participating investigators for use under ethics approved research protocols can be considered.
Journal Article
Tracheobronchial amyloidosis
by
Jivraj, Khalil
,
MacEachern, Paul R
,
Elliot, Tracy L
in
Adult
,
Amyloidosis - diagnostic imaging
,
Amyloidosis - pathology
2014
Journal Article
Self‐Expandable Metallic Stents in Nonmalignant Large Airway Disease
by
Tremblay, Alain
,
Dumoulin, Elaine
,
Fortin, Marc
in
Airway Obstruction - surgery
,
Anastomosis, Surgical
,
Bronchial Diseases - surgery
2015
Airway self‐expandable metallic stents (SEMS) were initially studied in malignant airway obstruction; however, their use in benign airway diseases has become progressively more frequent. This may be explained by their ease of insertion compared with silicone stents, which require rigid bronchoscopy for insertion. While initial experience with SEMS in benign disease suggested efficacy and promising short‐term safety profile, long‐term follow‐up revealed significant complication rates. In addition to a high complication rate, the management of these complications is made more difficult by the semipermanent nature of these devices. Reported complications include infection, granulation tissue formation, stent migration, stent fracture, airway perforation and fistula formation, as well as extension of the initial injury, potentially eliminating other therapeutic options such as surgical resection. Therefore, SEMS should only be used in nonmalignant large airway disease as a last resort for patients in whom other endoscopic methods, including silicone stents and dilations, as well as surgical options have failed or are technically not feasible.
Journal Article