Project description:BackgroundThe 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates. In 1993, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers.MethodsA total of 77 464 participants, aged 55-74 years, were randomly assigned to the intervention arm of the PLCO Cancer Screening Trial between November 8, 1993, and July 2, 2001. Participants received a baseline chest radiograph (CXR), followed by three annual single-view CXRs at the 10 US screening centers. Cancers were classified as screen detected and nonscreen detected (interval or never screened) and according to tumor histology. The positivity rates of screen-detected cancers and positive predictive values (PPVs) were calculated. Because 51.6% of the participants were current or former smokers, logistic regression analysis was performed to control for smoking status. All statistical tests were two-sided.ResultsCompliance with screening decreased from 86.6% at baseline to 78.9% at the last screening. Overall positivity rates were 8.9% at baseline and 6.6%-7.1% at subsequent screenings; positivity rates increased modestly with smoking risk categories (P(trend) < .001). The PPVs for all participants were 2.0% at baseline and 1.1%, 1.5%, and 2.4% at years 1, 2, and 3, respectively; PPVs in current smokers were 5.9% at baseline and 3.3%, 4.2%, and 5.6% at years 1, 2, and 3, respectively. A total of 564 lung cancers were diagnosed, of which 306 (54%) were screen-detected cancers and 87% were non-small cell lung cancers. Among non-small cell lung cancers, 59.6% of screen-detected cancers and 33.3% of interval cancers were early (I-II) stage.ConclusionsThe PLCO Cancer Screening Trial demonstrated the ability to recruit, retain, and screen a large population over multiple years at multiple centers. A higher proportion of screen-detected lung cancers were early stage, but a conclusion on the effectiveness of CXR screening must await final PLCO results, which are anticipated at the end of 2015.
Project description:Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer accounts for 75% to 80% of all lung cancers. There is an impetus to find a screening test that can detect non-small cell lung cancer in its early preclinical stages, when surgical resection is most likely to reduce lung cancer mortality. Although earlier randomized controlled trials of lung cancer screening using chest radiography and sputum cytology failed to show reduced lung cancer mortality, CT is a much more sensitive test for detecting small lung nodules, and has generated considerable enthusiasm as a potential contemporary screening tool for lung cancer.
Project description:Poor survival of lung cancer (LC) patients depends on several factors first of all the delay in the diagnosis, considering that the majority of patients have an advanced-stage disease at the time of diagnosis. In this context, use of screening to increase the percentage of early LC detection can play a crucial role. After the preliminary unsatisfactory experiences with chest X-rays and sputum cytology, low dose computed tomography (LDCT) has become the best method for LC screening. In particular, several randomized LDCT screening trials conducted in the last year showed significant reductions in LC mortality in high-risk subjects. This review focuses on both recent advances in LC screening and some open questions.
Project description:The National Lung Screening Trial (NLST) used risk factors for lung cancer (e.g., ?30 pack-years of smoking and <15 years since quitting) as selection criteria for lung-cancer screening. Use of an accurate model that incorporates additional risk factors to select persons for screening may identify more persons who have lung cancer or in whom lung cancer will develop.We modified the 2011 lung-cancer risk-prediction model from our Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to ensure applicability to NLST data; risk was the probability of a diagnosis of lung cancer during the 6-year study period. We developed and validated the model (PLCO(M2012)) with data from the 80,375 persons in the PLCO control and intervention groups who had ever smoked. Discrimination (area under the receiver-operating-characteristic curve [AUC]) and calibration were assessed. In the validation data set, 14,144 of 37,332 persons (37.9%) met NLST criteria. For comparison, 14,144 highest-risk persons were considered positive (eligible for screening) according to PLCO(M2012) criteria. We compared the accuracy of PLCO(M2012) criteria with NLST criteria to detect lung cancer. Cox models were used to evaluate whether the reduction in mortality among 53,202 persons undergoing low-dose computed tomographic screening in the NLST differed according to risk.The AUC was 0.803 in the development data set and 0.797 in the validation data set. As compared with NLST criteria, PLCO(M2012) criteria had improved sensitivity (83.0% vs. 71.1%, P<0.001) and positive predictive value (4.0% vs. 3.4%, P=0.01), without loss of specificity (62.9% and. 62.7%, respectively; P=0.54); 41.3% fewer lung cancers were missed. The NLST screening effect did not vary according to PLCO(M2012) risk (P=0.61 for interaction).The use of the PLCO(M2012) model was more sensitive than the NLST criteria for lung-cancer detection.
Project description:The Lung Screening Study was a multicenter controlled feasibility trial that randomly assigned subjects to undergo two rounds of screening with either low-dose spiral computed tomography (LDCT) or chest X-ray (CXR). Long-term follow-up was performed to evaluate any differences in lung-cancer-specific and all-cause mortality between arms. In 2000, subjects were randomly assigned at six screening centers. Linkage with the National Death Index was performed to ascertain long-term mortality for subjects. Median follow-up for mortality of the 1660 and 1658 subjects randomly assigned to LDCT and CXR, respectively, was 5.2 years. There were 32 and 26 deaths from lung cancer in the two groups, respectively, corresponding to lung cancer death rates of 3.84 and 3.10 per 1000 person-years, and a risk ratio of 1.24 (95% confidence interval = 0.74 to 2.08). The risk ratio for all-cause mortality was 1.20 (95% confidence interval = 0.94 to 1.54). These findings can contribute to the overall knowledge on LDCT lung cancer screening.
Project description:BackgroundLung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.MethodsThe pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.Results247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569).ConclusionsThe UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction.Trial registrationISRCTN 78513845.
Project description:BackgroundThe National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years.DesignThe Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n = 2376), with further randomization to annual (n = 1190) or biennial (n = 1186) LDCT for a median period of 6 years, or control arm (n = 1723) without intervention. Between 2005 and 2018, 39 293 person-years of follow-up were accumulated. The primary outcomes were 10-year overall and LC specific mortality. Landmark analysis was used to test the long-term effect of LC screening, beyond 5 years by exclusion of LCs and deaths that occurred in the first 5 years.ResultsThe LDCT arm showed a 39% reduced risk of LC mortality at 10 years [hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.39-0.95], compared with control arm, and a 20% reduction of overall mortality (HR 0.80; 95% CI 0.62-1.03). LDCT benefit improved beyond the 5th year of screening, with a 58% reduced risk of LC mortality (HR 0.42; 95% CI 0.22-0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49-0.94).ConclusionsThe MILD trial provides additional evidence that prolonged screening beyond 5 years can enhance the benefit of early detection and achieve a greater overall and LC mortality reduction compared with NLST trial.Clinicaltrials.gov identifierNCT02837809.
Project description:A complimentary biomarker test that can be used in combination with LDCT for lung cancer screening is highly desirable to improve the diagnostic capacity of LDCT and reduce the false-positive rates. Most importantly, the stage I lung cancer detection rate can be dramatically increased by the simultaneous use of a biomarker test with LDCT. The present study was conducted to evaluate 9G testTM Cancer/Lung's sensitivity and specificity in detecting Stage 0~IV lung cancer. The obtained results indicate that the 9G testTM Cancer/Lung can detect lung cancer with overall sensitivity and specificity of 75.0% (69.1~80.3) and 97.3% (95.0~98.8), respectively. The detection of stage I, stage II, stage III, and stage IV cancers with sensitivities of 77.5%, 78.1%, 67.4%, and 33.3%, respectively, at the specificity of 97.3% have never been reported before. The receiver operating characteristic curve analysis allowed us to determine the population-weighted AUC of 0.93 (95% CI, 0.91-0.95). These results indicate that the 9G testTM Cancer/Lung can be used in conjunction with LDCT to screen lung cancer. Furthermore, obtained results indicate that the use of 9G testTM Cancer/Lung with LDCT for lung cancer screening can increase stage I cancer detection, which is crucial to improve the currently low 5-year survival rates.