EarlyCDT-Lung Test Research Articles

Health Economic Evaluation of Lung Cancer Screening Using a Diagnostic Blood Test: The Early Detection of Cancer of the Lung Scotland (ECLS).

Diagnostic blood tests have the potential to identify lung cancer in people at high risk. We assessed the cost-effectiveness of a lung cancer screening intervention, using the EarlyCDT®-Lung Test (ECLS) with subsequent X-ray and low-dose chest CT scans (LDCT) for patients with a positive test result, compared to both usual care and LDCT screening for the target population. We conducted a model-based lifetime analysis from a UK NHS and personal social services perspective. We estimated incremental net monetary benefit (NMB) for the ECLS intervention compared to no screening and to LDCT screening. The incremental NMB of ECLS intervention compared to no screening was GBP 33,179 (95% CI: -GBP 81,396, GBP 147,180) and GBP 140,609 (95% CI: -GBP 36,255, GBP 316,612), respectively, for a cost-effectiveness threshold of GBP 20,000 and GBP 30,000 per quality-adjusted life year. The same figures compared with LDCT screening were GBP 162,095 (95% CI: GBP 52,698, GBP 271,735) and GBP 52,185 (95% CI: -GBP 115,152, GBP 219,711). The ECLS intervention is the most cost-effective screening alternative, with the highest probability of being cost-effective, when compared to no screening or LDCT screening. This result may change with modifications of the parameters, suggesting that the three alternatives considered in the main analysis are potentially cost-effective.

Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts.

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.

Assessment of background levels of autoantibodies as a prognostic marker for severe SARS-CoV-2 infection.

Background: Patients with more severe forms of SARS-CoV-2 exhibit activation of immunological cascades. Participants (current or ex-smokers with at least 20 years pack history) in a trial (Early Diagnosis of Lung Cancer, Scotland [ECLS]) of autoantibody detection to predict lung cancer risk had seven autoantibodies measured 5 years before the pandemic. This study compared the response to Covid infection in study participants who tested positive and negative to antibodies to tumour-associated antigens: p53, NY-ESO-1, CAGE, GBU4-5, HuD, MAGE A4 and SOX2. Methods: Autoantibody data from the ECLS study was deterministically linked to the EAVE II database, a national, real-time prospective cohort using Scotland’s health data infrastructure, to describe the epidemiology of SARS-CoV-2 infection, patterns of healthcare use and outcomes. The strength of associations was explored using a network algorithm for exact contingency table significance testing by permutation. Results: There were no significant differences discerned between SARS-CoV-2 test results and EarlyCDT-Lung test results (p = 0.734). An additional analysis of intensive care unit (ICU) admissions detected no significant differences between those who tested positive and negative. Subgroup analyses showed no difference in COVID-19 positivity or death rates amongst those diagnosed with chronic obstructive pulmonary disease (COPD) with positive and negative EarlyCDT results. Conclusions: This hypothesis-generating study demonstrated no clinically valuable or statistically significant associations between EarlyCDT positivity in 2013-15 and the likelihood of SARS-CoV-2 positivity in 2020, ICU admission or death in all participants (current or ex-smokers with at least 20 years pack history) or in those with COPD or lung cancer.

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging.

The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2 years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41–0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT.

Determinants of motivation to quit in smokers screened for the early detection of lung cancer: a qualitative study

BackgroundThe promotion of smoking cessation within lung cancer screening could lead to benefits for smoking-related disease and improve cost-effectiveness of screening. Little is known about how smokers respond to lung cancer screening and how this impacts smoking behaviour. We aimed to understand how lung cancer screening influences individual motivations about smoking, including in those who have stopped smoking since screening.MethodsThirty one long-term smokers aged 51–74 took part in semi-structured interviews about smoking. They had been screened with the EarlyCDT-Lung Test (13 positive result; 18 negative) as part of the Early Cancer Detection Test Lung Cancer Scotland Study. They were purposively sampled for interview based on their self-reported post-screening smoking behaviour. Eleven participants had stopped smoking since screening. Verbatim interview transcripts were analysed using thematic analysis.ResultsTwo key overarching themes were interpretations of screening test results and emotional responses to those interpretations. Participants’ understanding of the risk implied by their test result was often inaccurate, for example a negative result interpreted as an ‘all-clear’ from lung cancer and a positive result as meaning lung cancer would definitely develop. Those interpretations led to emotional responses (fear, shock, worry, relief, indifference) influencing motivations about smoking. Other themes included a wake-up call causing changes in perceived risk of smoking-related disease, a feeling that now is the time to stop smoking and family influences. There was no clear pattern in smoking motivations in those who received positive or negative test results. Of those who had stopped smoking, some cited screening experiences as the sole motivation, some cited screening along with other coinciding factors, and others cited non-screening reasons. Cues to change were experienced at different stages of the screening process. Some participants indicated they underwent screening to try and stop smoking, while others expressed little or no desire to stop.ConclusionsWe observed complex and individualised motivations about smoking following lung cancer screening. To be most effective, smoking cessation support in this context should explore understanding of screening test results and may need to be highly tailored to individual emotional responses to screening.

P3.13-020 A Pilot Study of the Autoantibodies to Tumor Antigens in Lung Cancer Using the EarlyCDT-Lung Test in Hong Kong

The EarlyCDT-Lung test detects autoantibodies to abnormal cell surface proteins in lung cancer patients. It has been studied in UK1 and USA2 in diagnosing lung cancer patients and has a sensitivity of up to 47%, specificity up to 90% and positive predictive value of 16%. It is a potential diagnostic test and when combines with radiological (Computed Tomography) test, the positive predictive value can be enhanced up to 72%3. We want to study the performance of the test in a predominantly Asian ethnic city. 1. Caroline J. Chapman et al. EarlyCDT®-Lung test: improved clinical utility through additional autoantibody assays. Tumor Biol. 2012; 33:1319–1326 2. JR Jett et al. Audit of the autoantibody test, EarlyCDT®-Lung, in 1600 patients: An evaluation of its performance in routine clinical practice. Lung Cancer 2014; 83:51–55 . 3. P Massion et al. Autoantibody Signature Enhances the Positive Predictive Power of Computed Tomography and Nodule-Based Risk Models for Detection of Lung Cancer Journal of Thoracic Oncology 2017; 12:578-584

Detection in blood of autoantibodies to tumour antigens as a case-finding method in lung cancer using the EarlyCDT\xae-Lung Test (ECLS): study protocol for a randomized controlled trial

BackgroundLung cancer is the most common cause of cancer related death worldwide. The majority of cases are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease which may allow tumour detection at an earlier stage thus altering prognosis.The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by X-ray and computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice?MethodsA randomised controlled trial of 12 000 participants in areas of Scotland targeting general practices serving patients in the most deprived quintile of the Scottish Index of Multiple Deprivation. Adults aged 50–75 who are at high risk of lung cancer and healthy enough to undergo potentially curative therapy (Performance Status 0–2) are eligible to participate. The intervention is the EarlyCDT®-Lung Test, followed by X-ray and CT in those with a positive result. The comparator is standard clinical practice in the UK. The primary outcome is the difference, after 24 months, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis. The secondary outcomes include: all-cause mortality; disease specific mortality; a range of morbidity outcomes; cost-effectiveness and measures examining the psychological and behavioural consequences of screening.Participants with a positive test result but for whom the CT scan does not lead to a lung cancer diagnosis will be offered 6 monthly thoracic CTs for 24 months. An initial chest X-ray will be used to determine the speed and the need for contrast in the first screening CT. Participants who are found to have lung cancer will be followed-up to assess both time to diagnosis and stage of disease at diagnosis.DiscussionThe study will determine the clinical and cost effectiveness of EarlyCDT®-Lung Test for early lung cancer detection and assess its suitability for a large-scale, accredited screening service. The study will also assess the potential psychological and behavioural harms arising from false positive or false negative results, as well as the potential benefits to patients of true negative EarlyCDT lung test results. A cost-effectiveness model of lung cancer screening based on the results of the EarlyCDT Lung Test study will be developed.Trial registrationNCT01925625. August 19, 2013

P1.03-045 Screening for Lung Cancer with Early CDT-Lung Blood Biomarkers and Computed Tomography

The Early Cancer Detection Test (CDT)-Lung is a serum-based biomarker consisting of a panel of tumor-associated autoantibodies that has been shown to detect lung cancer. We hypothesized that this biomarker when used in combination with a low-dose CT (LDCT) in screening of an at-risk population would increase the detection of early stage lung cancer. A prospective study of 1,600 subjects at high risk for lung cancer was designed. Eligibility criteria included persons 50-75 years of age, current or former smokers of ≥ 20 pack years and ˂ 10 years since quit smoking. Those with a history of lung cancer in first-degree relative(s) and any history of smoking were included. Exclusion criteria were any history of cancer within 10 years (except skin cancer), any use of oxygen, and life expectancy of < 5 years. Those fitting inclusion criteria received the Early CDT-Lung blood test and a LDCT. A nodule of ≥ 3mm was considered as a positive scan. The Early CDT-Lung test was considered positive if any one of the seven autoantibodies was positive. Telephonic follow-up was conducted over two years. From May 2012 through June 2016, 1235 individuals were enrolled. The cohort median age was 59 years with 55% female and 45% male gender distribution. Fifty-two per cent were current smokers while 48% were former smokers. Seventy-one per cent of the LDCTs were negative for any lung nodule while 29% were positive. The Early CDT-Lung biomarker was positive in 88 (7%) of participants. In those with a positive LDCT (n=352), the biomarker was positive in 30 (8.5%). As of June 30, 2015, there have been seven confirmed lung cancers: two limited stage small cell, two Stage IB adenocarcinoma (ACA), and three Stage IA (two ACA and one squamous cell). The Early CDT-Lung blood test was positive in 2 of the 7 (29%) total cancers, both stage 1A. Early CDT-Lung was positive in 2 of 5 (40%) Stage IA/B lung cancers in total. Early CDT-Lung was negative in the two small cell cancers. There are 58 Early CDT-Lung biomarker positive individuals with a LDCT without nodules (NCT01700257). The Early CDT-Lung biomarker was more likely to be positive in patients with nodules and lung cancer cases, particularly early stage lung cancer. Accrual to the study and follow-up of 58 biomarker positive but LDCT negative participants continues.

P1.03-077 Analysis of the Early CDT-Blood Biomarker for Lung Cancer in Higher vs. Lower Risk Cohorts

The Early Cancer Detection Test (CDT)-Lung Cancer Screening (LCS) Study is a prospective, lung cancer screening study testing the hypothesis that a serum biomarker consisting of a panel of seven cancer-associated autoantibodies, in combination with a low-dose CT (LDCT), would increase detection of early stage lung cancer. We analyzed nodules rates and lung cancer in “higher risk” individuals who meet the USPSTF LCS criteria (http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening) and “lower risk” individuals who do not meet these criteria. The EarlyCDT LCS study eligibility criteria included persons 50-75 years of age, current or former smokers of ≥ 20 pack years, former smokers have < 10 years since quit smoking. Additionally, those with a history of lung cancer in first-degree relative(s) and any history of smoking were also included. Exclusion criteria included any history of cancer within 10 years (except skin cancer), any use of oxygen, or life expectancy < 5 years. The EarlyCDT-Lung test was considered positive if any one of the seven autoantibodies was positive. From May 2012 through June 2016, 1235 individuals were enrolled (final target 1600). The median age was 59 years, 55% were female and 45% were male. Fifty-two per cent were current smokers while 48% were former smokers. Fifty-three percent of participants were higher risk and 47% were lower risk. The EarlyCDT-Lung was positive in 8% of higher risk individuals and 6% of lower risk individuals. Thirty-five per cent of higher risk individuals had nodules on LDCT while 27% of lower risk participants had nodules on LDCT. The EarlyCDT-Lung blood test was positive in 91 patients, 77 were higher risk and 34 were lower risk. There were 7 lung cancers, all in the higher risk group, resulting in a lung cancer rate of 1.07% in the higher risk group. The median pack years of individuals with lung cancer was 60 and the median age was 64 years. Two of the 7 lung cancer patients were positive for the EarlyCDT test. The relative risk of lung cancer in patients with a positive EarlyCDT test was 5.5 for the entire cohort and 4.5 for the higher risk group for lung cancer. There were more total nodules in the higher risk group compared to the lower risk group. There were more lung cancers in the higher risk group compared with the lower risk group. A positive EarlyCDT test is associated with an increased risk of lung cancer.

P2.06-038 An RCT of the Detection of Autoantibodies to Tumor Antigens in Lung Cancer Using the EarlyCDT-Lung Test in Scotland (ECLS) in 12 208 Study Subjects: Topic: LAB, Other

The majority (around 80%) of cases of lung cancer are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease with a specificity of 93% which may allow tumor detection at an earlier stage thus altering prognosis. The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice? We have completed recruitment with 12 208 study subjects randomised by June 2016. A randomized controlled trial in general practices serving areas of Scotland representing the most socially disadvantaged quintile based on Scottish Index of Multiple Deprivation. Adults aged 50 to 75 at high risk for lung cancer (>20 pack years) and healthy enough to undergo potentially curative therapy (Performance Status 0-2) are eligible to participate. The intervention is the EarlyCDT®-Lung Test, followed by X-ray and CT in those with a positive result. The comparator is standard clinical practice in the UK. The primary outcome is the difference, after 24 months, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis. The secondary outcomes include: all-cause mortality; disease specific mortality; a range of morbidity outcomes; cost-effectiveness and measures examining the psychological and behavioural consequences of screening. Participants with a positive test result but for whom the CT scan does not lead to a lung cancer diagnosis have been offered 6 monthly thoracic CTs for 24 months. An initial chest X-ray was used to determine the speed and the need for contrast in the first screening CT. Participants who were found to have lung cancer are being followed-up to assess both time to diagnosis and stage of disease at diagnosis. 575/ 6 120 (9.8%) of the test group had a positive test with 207 found to have lung nodules > 8mm. 16 lung cancers have been detected, 12(75%) of which are early stage and 11 abnormalities are undergoing further investigation. At this stage of the trial we have no outcome data for the comparison group. The study will determine the EarlyCDT-Lung test’s clinical and cost effectiveness. It will also assess potential morbidity arising from the test and potential harms and benefits of EarlyCDT-Lung test screening.

The challenge of small lung nodules identified in CT screening: can biomarkers assist diagnosis?

Various biomarkers have been developed as noninvasive tests to indicate the presence of lung cancer in asymptomatic persons, and in particular to provide evidence as to whether indeterminate lung nodules detected by screening are malignant. We performed an overview of the range of biomarkers reported in the literature and described those that can complement low-dose computed tomography screening. Several have promising sensitivity and specificity. However to our knowledge, only three techniques have reached the prospective screening phase (phase 4) of the five-phase biomarker development process. Two miRNA signatures (the miR-Test for serum and the miRNA signature classifier test for plasma) are being assessed in prospective screening trials, as is the EarlyCDT-Lung test based on autoantibodies. All will need to undergo prospective studies to determine their ability to improve outcomes before they can become an established adjunct to lung cancer control strategies.

Audit of the autoantibody test, EarlyCDT®-Lung, in 1600 patients: An evaluation of its performance in routine clinical practice

ObjectivesEarlyCDT®-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. MethodsClinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. ResultsSix month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. ConclusionsEarlyCDT-Lung has been extensively tested and validated in case–control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer.

Antigen Positivity in the Early CDT-Lung Test by Stage and Histological Subtype of Lung Cancer

PURPOSE: EarlyCDT-LungTM detects autoantibodies to a panel of six lung cancer-associated antigens with sensitivity of 40% and specificity of 90%. EarlyCDT-Lung has been shown to aid in detecting early-stage disease just as well as late-stage disease in high-risk individuals. The positivity rate for each antigen by stage of disease and histological subtype are presented.

Reproducibility of autoantibody measurements in normal individuals using the Early CDT-Lung test.

e17522 Background: The Early CDT-Lung test is an assay, intended as a tool for risk stratification in a population at high risk for lung cancer. The test measures autoantibodies (AAb) against a panel of six tumor-associated antigens (p53, SOX2, CAGE, NY-ESO-1, GBU4-5 and Annexin 1). The aim of this study was to investigate the variability between repeated samples from the same patient. Methods: Serial serum samples were collected once a week for 4 weeks from premenopausal female smokers (n=46, mean age = 39.9 years) and once every 2 weeks for 4 weeks from post-menopausal female smokers (n=19, mean age = 54.7 years) and male smokers (n=10, mean age=58.4 years). Local ethical approval had been given for the collection. Comparisons between weeks were performed using paired t-tests. Coefficients of variation (CVs) for between-sampling-time (within-patient) reproducibility were compared with historical estimates of between-assay CVs. Results: Paired t-tests showed no significant differences between the paired samples from male smokers. No significant differences were observed between the first sample taken from premenopausal women and any of the subsequent 3 samples. The only significant difference out of 30 t-tests performed was p53 levels in samples from post-menopausal women taken 2 weeks apart (p=0.021). These findings showed that there was no directional trend over time for the patient set while graphics showed constant AAb levels over time within-patient. The comparison of CVs showed that between-sampling-time reproducibility was no higher than that for between-assay CVs for any of the three groups. This confirmed that the within-patient AAb level was not varying over the monthly cycle. Conclusions: The Early CDT-Lung test demonstrates a high degree of reproducibility in measurements of serial samples taken from the same patient. Cyclic hormonal changes do not appear to affect assay results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncimmune Oncimmune Oncimmune, Oncolytics Biotech, Oncommune Oncimmune