Lung Cancer Screening Trial Research Articles

Impact of Timeliness of Surgical Treatment on the Outcomes of Patients with Non-metastatic Non-small Cell Lung Cancer: Findings From the PLCO Trial.

This study aimed to assess the impact of timeliness of surgical resection among patients with non-metastatic non-small cell lung cancer (NSCLC) treated with upfront surgery. Cases with confirmed non-metastatic NSCLC diagnosis treated with upfront surgery within the cohort of participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were included in the current study. Multivariate logistic regression analysis was used to assess factors predicting time from diagnosis to surgical resection. Multivariate Cox regression analysis was used to assess factors affecting lung cancer-specific survival. A total of 1022 patients were included in the current analysis. A total of 873 patients underwent surgical resection within 30days of diagnosis, while a total of 149 patients underwent surgical resection after 30days from diagnosis. Through multivariate logistic regression analysis, the following factors were predictive for longer time to surgical resection: older age (odds ratio 1.077; 1.043-1.112; P < 0.001) and advanced stage at presentation (odds ratio 1.923; 1.056-3.502; P = 0.033). Through multivariate Cox regression analysis, time to surgical resection (≤30days vs. >30days) did not affect lung cancer-specific survival (hazard ratio 0.999; 0.739-1.350; P = 0.994). When the same multivariate analysis was repeated using time to surgical resection as a continuous variable, there was no impact on lung cancer-specific survival (hazard ratio 1.002; 0.997-1.007; P = 0.383). Time to surgical resection did not affect survival outcomes of non-metastatic NSCLC patients. Current therapy timeline targets need to be reviewed in our healthcare systems in order to redirect and prioritize the existing resources.

Relation between tobacco control policies and population at high risk of lung cancer in the European Union

IntroductionLung cancer accounts for nearly 2 million deaths per year worldwide, the majority of cases due to smoking as the main risk factor associated. The aim of this study was to assess the relation between the level of implementation of tobacco control policies and the population at high risk of lung cancer in the European Union (EU). MethodsThe Special Eurobarometer 458 “Attitudes of Europeans towards tobacco and electronic cigarettes”, conducted in 2017, and the Tobacco Control Scale (TCS) 2010, 2013, and 2016 were the sources of our data. High risk of lung cancer was defined by the inclusion criteria in the National Lung Screening Trial (NLST) and the Dutch-Belgian Lung Cancer Screening Trial (NELSON), the largest lung cancer screening trials carried out in the US and the EU. We calculated Spearman's rank correlation coefficients (rsp) and fitted multilevel generalized linear mixed models using the quasi-Poisson family to assess the correlation at the national level and analyze the association at the individual level, respectively, between the scores in the TCS (higher scores means better implementation of tobacco control policies) and the proportion of individuals at high risk of lung cancer in member states of the EU. ResultsThe scores in the TCS 2010 were statistically negatively correlated with the current proportion of ever and former smokers at high risk according to NELSON criteria (−0.41; 95%CI −0.68, −0.04 and −0.49; 95%CI −0.73, −0.13, respectively). We observed statistically significant inverse associations between the scores in the TCS 2010 for the highest quartiles and the proportion of individuals at high risk of lung cancer according to both criteria. Non-statistically significant negative correlations and inverse associations were observed with other TCS. ConclusionThere is a lag between the implementation of tobacco control policies and the reduction of the rates of high risk of lung cancer. Member states should reinforce comprehensive tobacco control policies to reduce the population at high risk of lung cancer in the EU.

Deep Learning to Assess Long-term Mortality From Chest Radiographs

Chest radiography is the most common diagnostic imaging test in medicine and may also provide information about longevity and prognosis. To develop and test a convolutional neural network (CNN) (named CXR-risk) to predict long-term mortality, including noncancer death, from chest radiographs. In this prognostic study, CXR-risk CNN development (n = 41 856) and testing (n = 10 464) used data from the screening radiography arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 52 320), a community cohort of asymptomatic nonsmokers and smokers (aged 55-74 years) enrolled at 10 US sites from November 8, 1993, through July 2, 2001. External testing used data from the screening radiography arm of the National Lung Screening Trial (NLST) (n = 5493), a community cohort of heavy smokers (aged 55-74 years) enrolled at 21 US sites from August 2002, through April 2004. Data analysis was performed from January 1, 2018, to May 23, 2019. Deep learning CXR-risk score (very low, low, moderate, high, and very high) based on CNN analysis of the enrollment radiograph. All-cause mortality. Prognostic value was assessed in the context of radiologists' diagnostic findings (eg, lung nodule) and standard risk factors (eg, age, sex, and diabetes) and for cause-specific mortality. Among 10 464 PLCO participants (mean [SD] age, 62.4 [5.4] years; 5405 men [51.6%]; median follow-up, 12.2 years [interquartile range, 10.5-12.9 years]) and 5493 NLST test participants (mean [SD] age, 61.7 [5.0] years; 3037 men [55.3%]; median follow-up, 6.3 years [interquartile range, 6.0-6.7 years]), there was a graded association between CXR-risk score and mortality. The very high-risk group had mortality of 53.0% (PLCO) and 33.9% (NLST), which was higher compared with the very low-risk group (PLCO: unadjusted hazard ratio [HR], 18.3 [95% CI, 14.5-23.2]; NLST: unadjusted HR, 15.2 [95% CI, 9.2-25.3]; both P < .001). This association was robust to adjustment for radiologists' findings and risk factors (PLCO: adjusted HR [aHR], 4.8 [95% CI, 3.6-6.4]; NLST: aHR, 7.0 [95% CI, 4.0-12.1]; both P < .001). Comparable results were seen for lung cancer death (PLCO: aHR, 11.1 [95% CI, 4.4-27.8]; NLST: aHR, 8.4 [95% CI, 2.5-28.0]; both P ≤ .001) and for noncancer cardiovascular death (PLCO: aHR, 3.6 [95% CI, 2.1-6.2]; NLST: aHR, 47.8 [95% CI, 6.1-374.9]; both P < .001) and respiratory death (PLCO: aHR, 27.5 [95% CI, 7.7-97.8]; NLST: aHR, 31.9 [95% CI, 3.9-263.5]; both P ≤ .001). In this study, the deep learning CXR-risk score stratified the risk of long-term mortality based on a single chest radiograph. Individuals at high risk of mortality may benefit from prevention, screening, and lifestyle interventions.

Airflow limitation and survival after surgery for non-small cell lung cancer: Results from a systematic review and lung cancer screening trial (NLST-ACRIN sub-study)

ObjectiveLung cancer remains the single greatest cause of cancer mortality where surgery for early stage non-small cell lung cancer achieves the greatest survival. While there is growing optimism for better outcomes with screening using annual computed tomography, the impact of co-existing airflow limitation on survival remains unknown.To compare survival in non-small cell lung cancer patients undergoing surgery stratified according to the presence or absence of pre-surgery airflow limitation. Materials and MethodsWe undertook a systematic literature search of non-screen lung cancer that encompassed studies reported between January 1946 and January 2017. Full-text articles were identified following eligibility scoring, with data extracted and analysed using a standardised analytical method (PRISMA). The results of this systematic review in non-screen lung cancers were compared to real-world results from a lung cancer screening cohort (N = 10,054), where outcomes following surgery could be compared after stratification according to pre-surgery airflow limitation. ResultsIn the systematic review, 6899 subjects were included from 10 studies; 7 were retrospective, 3 were prospective. Overall survival was 950 (44%) in 2144 people with COPD and 2597 (55%) from 4755 controls (unadjusted P value <0.001). However, the overall meta-analysed random effects odds ratio for overall survival (N = 10) and 5-year survival (N = 4) comparing those with and without COPD was 0.91 (95% CI = 0.84–1.00) and 0.99 (95% CI = 0.79–1.24) respectively. There were no signs of significant heterogeneity (I2 = 19.1%, P = 0.27) nor publication bias as assessed by funnel plot and Egger’s test (P = 0.19). In the lung cancer screening sub-study of 10,054 screening participants we found no difference in 5-year survival in those with and without airflow limitation (84% and 81% respectively, P = 0.64). ConclusionSurvival after surgery for non-small cell lung cancer is comparable between those with and without spirometry evidence of airflow limitation. This finding was replicated in lung cancer diagnosed during screening.

Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial

BackgroundEstimation of the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs.MethodsData from the UK Lung Cancer...

Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Endometrial cancer is the most common gynecological cancer in the United States. However, no early detection test exists for asymptomatic women at average risk for endometrial cancer. We sought to identify early detection biomarkers for endometrial cancer using prediagnostic serum. We performed a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (n= 78,216), including 112 incident endometrial cancer cases and 112 controls. Prediagnostic serum was immunodepleted of high-abundance proteins and digested with sequencing grade porcine trypsin via pressure cycling technology. Quantitative proteomics and phosphoproteomics was performed using high-resolution liquid chromatography-tandem mass spectrometry and highly multiplexed isobaric mass tag combined with basic reversed-phase liquid chromatography. A set of proteins able to predict cancer status was identified with an integrated score assessed by receiver-operator curve analysis. Mean time from blood draw to endometrial cancer diagnosis was 3.5 years (SD, 1.9 years). There were 47 differentially abundant proteins between cases and controls (P < .05). Protein alterations with high predictive potential were selected by regression analysis and compiled into an aggregate score to determine the ability to predict endometrial cancer. An integrated risk score of 6 proteins was directly related to disease incidence in cases with blood draw ≤2 years, >2 years to ≤5 years or >5 years prior to cancer diagnosis. The integrated score distinguished cases from controls with an area under the curve of 0.80 (95% confidence interval, 0.72-0.88). An integrated score of 6 proteins using prediagnostic serum from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial distinguishes postmenopausal endometrial cancer cases from controls. Validation is needed to evaluate whether this test can improve prediction or detection of endometrial cancer among postmenopausal women.

Stratifying Ovarian Cancer Risk Using Personal Health Data.

Purpose: Screening the general population for ovarian cancer is not recommended by every major medical or public health organization because the harms from screening outweigh the benefit it provides. To improve ovarian cancer detection and survival many are looking at high-risk populations who would benefit from screening.Methods: We train a neural network on readily available personal health data to predict and stratify ovarian cancer risk. We use two different datasets to train our network: The National Health Interview Survey and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.Results: Our model has an area under the receiver operating characteristic curve of 0.71. We further demonstrate how the model could be used to stratify patients into different risk categories. A simple 3-tier scheme classifies 23.8% of those with cancer and 1.0% of those without as high-risk similar to genetic testing, and 1.1% of those with cancer and 24.4% of those without as low risk.Conclusion: The developed neural network offers a cost-effective and non-invasive way to identify those who could benefit from targeted screening.

Abstract 609: Vitamin D binding protein and risk of renal cell carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract Introduction/Study purpose: Vitamin D binding protein (DBP) is the major carrier of vitamin D in circulation. In addition to its role in vitamin D transport, DBP has several other biologic mechanisms that may be relevant to cancer risk including macrophage activation, apoptosis, and angiogenesis. Although previous studies have demonstrated no association between vitamin D and RCC, our group has conducted two previous studies which found strong inverse associations between DBP and RCC. We undertook the current analysis to replicate our findings in a different study population. Methods: We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Cases (n=323) were matched 1:1 to controls on age (+/- 1 year), race, date of blood collection (+/- 30 days) and sex. We performed conditional logistic regression to estimate the odds ratios and 95% confidence intervals for the association between quartiles of circulating DBP and risk of RCC. In addition to conditioning on the matching factors, multivariable models were further adjusted for history of diabetes or hypertension, family history of renal cancer, body mass index (BMI), and smoking status. Additionally, we performed stratified analyses by sex, family history of renal cancer, BMI, smoking status, and tumor stage at diagnosis. Results: We observed a statistically significant positive association between DBP and RCC that persisted after multivariable adjustment (mv-adj Q4 vs. Q1 OR=3.1, 95% CI=1.8-5.6; p-trend &amp;lt;0.0001). Sensitivity analyses were performed removing matched pairs where the case was diagnosed within 2 years of blood collection or experienced a large weight loss (&amp;gt;40 lbs), with little effect on the overall trend (Q4 vs. Q1 OR=2.5 CI=1.4-4.6 p-trend=&amp;lt;0.0001). Conclusions: In the present study, those with higher serum concentrations of DBP were at increased risk of RCC, which differs from previously-published findings. Further research is necessary to determine the true association between DBP and risk of RCC, and whether different DBP phenotypes via GC variation may have different associations with risk of RCC. Note: This abstract was not presented at the meeting. Citation Format: Tyler B. Kratzer, Alison M. Mondul, Stephanie J. Weinstein, Demetrius Albanes. Vitamin D binding protein and risk of renal cell carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 609.

Abstract 604: Biomarkers of amino acid metabolism and endometrial cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

Abstract Background: Incidence and mortality rates for endometrial cancer have steadily increased during the past decade. Beyond the well-known risk factors of obesity and unopposed estrogen menopausal hormone therapy (MHT), our understanding of the molecular etiology of this disease is limited and few biomarkers for risk are identified. To address this data gap, we explored circulating markers of amino acid metabolism and endometrial cancer risk—with specific interest in assessing whether the associations with branch chain amino acids (BCAAs) differed by known endometrial cancer risk factors. Methods: We used data from a nested case-control study within the screening arm of the PLCO trial (353 endometrial cancer cases, 353 controls, age 55-74 years at enrollment). We measured absolute concentrations of amino acid metabolism markers in pre-diagnostic serum using targeted mass spectrometry assays. Conditional and unconditional logistic regression adjusted for potential confounders (and matching factors in the latter) was used to estimate associations between these circulating markers and endometrial cancer overall, by body mass index (BMI), and by MHT use at baseline. We evaluated heterogeneity across these groups via likelihood ratio tests (p for interaction [p-int]). Results: In the full population, associations with endometrial cancer were generally masked/not identified, but we noted substantial effect modification by MHT use and BMI. A doubling in endometrial cancer risk was suggested with the highest concentrations of BCAAs, but only among women not using MHT (odds ratio and 95% confidence interval for the highest quintile [Q5] versus lowest [Q1]: leucine 1.87, 0.91–3.83; isoleucine 2.44, 1.17–5.09; and valine 1.86, 0.89–3.87; p-int &amp;lt;0.15 for all). We similarly noted that high levels of leucine (Q5 v. Q1: 3.26, 0.96–11.08, p-int 0.39) and valine (Q5 v. Q1: 6.40, 1.49–27.47, p-int 0.08) were associated with risk among obese women, but not those with normal BMIs. The highest levels of 3-hydroxyisobutyrate, a bioactive valine precursor, doubled risk among non-MHT users (CI 1.09–4.51, p-int &amp;lt;0.05) and quadrupled it among obese women (CI 1.45–14.86, p-int 0.33). High proline levels were associated with 4- to 7-fold increases in risk among non-MHT users (CI 1.68–10.01) and obese women (CI 2.11–26.81), respectively (p-int&amp;lt;0.05 for both). Conclusions: Our findings suggest that the regulation of BCAA metabolism may be involved in endometrial carcinogenesis, but this influence depends on other risk factors for the disease. Use of MHT overshadowed potential risks with most markers evaluated, and we identified increased risks associated with a variety of markers only among obese women. Amino acids play crucial roles in cellular energy metabolism and our results highlight the importance of finding ways to maintain and improve metabolic health in postmenopausal women. Citation Format: Kara A. Michels, Stephanie J. Weinstein, Nicolas Wentzensen, Ruth M. Pfeiffer, Britton Trabert. Biomarkers of amino acid metabolism and endometrial cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 604.

Abstract 638: Association between calcium intake and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

Abstract Pancreatic cancer is a leading cause of cancer death in the U.S. and its etiology remains largely unclear. As most patients are diagnosed with an advanced, unresectable disease, primary prevention remains a priority for reducing its incidence and mortality. Although ecological, migrant, and temporal trend studies have shown that diet plays a role in the occurrence of pancreatic cancer, few nutrients that alter its risk have been identified from epidemiologic studies. The present study thus sought to investigate intakes of calcium and fat, adiposity, and their potential interactions in relation to pancreatic cancer risk among participants in the PLCO trial. Usual dietary intake among the participants was assessed with Dietary Questionnaire (DQX) at baseline and Dietary History Questionnaire (DHQ) around their third anniversary of randomization. Of 58,477 participants who completed the DQX, 279 cases of pancreatic cancer were documented during a median follow-up of 12.2 years. A total of 101,721 participants responded to the DHQ and gave risk to 380 cases of pancreatic cancer during a median follow-up of 8.9 years. Cox proportional hazards regression was performed to estimate hazard ratios (HR) and 95% Confidence intervals (CI) for pancreatic cancer in relation to total and dietary intake of calcium, intake of fat, and body mass index (BMI). After adjustment for established and suspected confounders, there was a suggestive inverse association between total calcium intake assessed from both food frequency questionnaires and risk of pancreatic cancer [HR (95% CI) for quartile (Q) 2, Q3, and Q 4 vs. Q1: 0.93 (0.67, 1.30), 0.86 (0.60, 1.24), and 0.71 (0.46,1.09); p-trend, 0.11) for DQX and 0.96 (0.72, 1.26), 0.99 (0.74, 1.33), and 0.72 (0.52, 1.01); p-trend, 0.08) for DHQ]. Overall, this inverse association was stronger or its linear trend in reduced risk across the quartiles of total calcium intake was more apparent among overweight participants (BMI: &amp;gt;25-&amp;lt;30) [e.g. HR (95% CI) for Q2, Q3, and Q4 vs. Q1: 0.91 (0.60,1.38), 0.84 (0.54, 1.30), and 0.72 (0.44, 1.18); p-trend, 0.07) for DHQ]. Among the participants with the highest fat intake (Q4) derived from the DHQ, those with the highest intake of total calcium (Q4) experienced a 65% reduced risk of pancreatic cancer compared with those with the lowest intake (Q1) [HR (95% CI): 0.35 (0.17, 0.68)]. However, the possibility of chance finding for this significant risk reduction could not be ruled out due to multiple comparisons. In addition, no appreciable associations of calcium intake from both dietary and supplemental sources with pancreatic cancer risk was observed. In summary, the present study offers suggestive evidence that total calcium intake was associated with a reduced risk of pancreatic cancer and that this potential benefit may be more pronounced among overweight subjects. Citation Format: Maggie Hoyt, Jianjun Zhang. Association between calcium intake and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 638.

Abstract 611: MYC DNA methylation in prostate tumor tissue is associated with tumor aggressiveness

Abstract We previously reported an increased risk of aggressive, but not non-aggressive, prostate cancer associated with pre-diagnostic blood DNA methylation levels in exon 3 of the MYC oncogene among Caucasian men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. In the present study, we aimed to investigate MYC DNA methylation in prostate tissue in relation to tumor aggressiveness (based on Gleason score). We also aimed to investigate whether MYC methylation in prostate tissue is associated with race or tumor/normal status. We accessed formalin-fixed, paraffin-embedded prostate tumor and normal tissue from 50 Caucasian and 50 African American prostate cancer patients that underwent radical prostatectomy at the University of Maryland; for each race group, we selected 25 patients with a Gleason score of 7 and 25 with a Gleason score of 6. We systematically selected the most recent samples, and year of surgery for our patients ranged from 2001-2017. Age at surgery ranged from 42-75 years. We used pyrosequencing to measure DNA methylation at six CpG sites in MYC exon 3 (Chr8:128753145 - Chr8:128753221). We excluded 11 patients for whom the assays failed, resulting in a final sample size of 43 African American and 46 Caucasian men. The six CpG sites demonstrated moderate correlations with one another in tumor tissue (Spearman rho: 0.30-0.60, p-value&amp;lt;0.01 for all pairings). Correlations between the CpG sites were less pronounced in the normal tissue samples (Spearman rho: -0.08-0.57) and five pairs were no longer significantly correlated. We used paired t-tests to evaluate differences in MYC DNA methylation between tumor and normal samples from the same patients, and unpaired t-tests to evaluate differences by Gleason score and race. We observed significantly higher MYC DNA methylation for all six CpG sites in the normal compared to the tumor samples (p&amp;lt;0.05). The difference in mean percent methylation between normal and tumor for the six sites ranged from 2.3 to 16.3 percentage points. In the tumor samples, we also observed significantly higher MYC DNA methylation for patients with a Gleason score of 6 compared to those with a Gleason score of 7 for three of the CpG sites. These included Chr8:128753145 (mean percent methylation for Gleason 6 group=89.0%; mean for Gleason 7=83.6%; t-test p-value=0.002), Chr8:128753154 (mean for Gleason 6=87.7%; mean for Gleason 7=81.7%; t-test p-value=0.004) and Chr8:128753200 (mean for Gleason 6=82.6%; mean for Gleason 7=78.8%; t-test p-value=0.02). Also in tumor tissue, we observed borderline significantly higher DNAm at Chr8:128753151 for African American than Caucasian men (mean for African American men=79.1%; mean for Caucasian men=73.7%; t-test p-value=0.06); no other CpG sites displayed differences by race. Our results provide further evidence for a role of altered MYC DNA methylation in aggressive prostate cancer. Citation Format: Kathryn Hughes Barry, Kareshma Mohanty, Gary Rose, Ashley Cellini, Nicholas Ambulos, Jing Yin, Liying Yan, Matthew Poulin, Ann Meyer, Yuji Zhang, Søren Bentzen, Allen Burke, Arif Hussain, Sonja I. Berndt. MYC DNA methylation in prostate tumor tissue is associated with tumor aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 611.

Abstract 3329: Lung cancer screening initiative and identification of novel blood biomarkers for early detection of lung cancer

Abstract In lung cancer, 81% of patients detected are late-stage, since early-stage patients are generally asymptomatic. Winnebago County has a 14% higher mortality rate for lung cancer when compared to the national rate; hence, to improve early detection of lung cancer in the Winnebago County, we implemented low-dose computed tomography (LDCT) screening. Currently, LDCT is used to detect lung cancer at early-stages, and the CDC has proposed new guidelines for early screening of lung cancer in individuals between 55-77 years of age with a 30 pack/year smoking history. Using circulating DNA from lung cancer patients and examining changes in methylation patterns in genes that are expressed in lung cancer patients can be used for early detection. Epidermal growth factor receptor (EGFR) is shown to be expressed in lung cancer patients’ serum in all stages; hence, it can be used as a potential biomarker for early detection. To improve early detection of lung cancer in the Winnebago County, we educated physicians/smokers about LDCT screenings to promote early detection of lung cancer. We evaluated the number of LDCTs performed and recorded the number of lung cancer cases detected in the Winnebago County between June 2015 to October 2017. To explore EGFR as a promising biomarker, plasma was separated from whole blood and collected. Circulating DNA was extracted with the MagMax cell-free circulating kit and bisulfite converted. Identification of percent methylation patterns in the EGFR promoter region in CpG islands was obtained after next generation sequencing (NGS) followed by bioinformatics analysis. In our study, 1,116 LDCT screenings occurred in the Winnebago County. Lung cancer was diagnosed in 19 patients, out of which 11 patients (57.8%) were early-stage patients. We detected 45.4% of patients screened that were present with nodules compared to 24.2% of patients in the National Lung Cancer Screening Trial. We observed that 1.70% of patients referred for LDCT screening were diagnosed with lung cancer, compared to 0.87% of patients in the National Lung Cancer Screening Trial. This may be due to the higher incidence of smoking in Winnebago County (18%) compared to the nation (15.5%). Our screening study had 96.3% false positives, which is comparable (96.4%) to the results obtained in the National Lung Cancer Screening Trial. Using NGS, methylation in the promoter region of EGFR was studied using degenerate EGFR primers. In the promoter region of EGFR, our analysis showed that there are regions of hypermethylation (68-86%) in three CpG islands in sequences at the beginning of the promoter (8-241 bases). However, there was hypomethylation (6-21%) at four CpG island further downstream (375-689 bases from the beginning of the promoter). Currently we are studying the methylation patterns in normal subjects to determine whether these regions which could be used as predictive biomarkers for early detection. Citation Format: Adijan Kuckovic, Joseph Berei, Shylendra Sreenivasappa, Joseph Ross, Sandra Martell, Connie Vitali, William Schulz, Neelu Puri. Lung cancer screening initiative and identification of novel blood biomarkers for early detection of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3329.

Lung cancer mortality reduction by LDCT screening-Results from the randomized German LUSI trial.

In 2011, the U.S. National Lung Cancer Screening Trial (NLST) reported a 20% reduction of lung cancer mortality after regular screening by low-dose computed tomography (LDCT), as compared to X-ray screening. The introduction of lung cancer screening programs in Europe awaits confirmation of these first findings from European trials that started in parallel with the NLST. The German Lung cancer Screening Intervention (LUSI) is a randomized trial among 4,052 long-term smokers, 50-69 years of age, recruited from the general population, comparing five annual rounds of LDCT screening (screening arm; n = 2,029 participants) with a control arm (n = 2,023) followed by annual postal questionnaire inquiries. Data on lung cancer incidence and mortality and vital status were collected from hospitals or office-based physicians, cancer registries, population registers and health offices. Over an average observation time of 8.8 years after randomization, the hazard ratio for lung cancer mortality was 0.74 (95% CI: 0.46-1.19; p = 0.21) among men and women combined. Modeling by sex, however showed a statistically significant reduction in lung cancer mortality among women (HR = 0.31 [95% CI: 0.10-0.96], p = 0.04), but not among men (HR = 0.94 [95% CI: 0.54-1.61], p = 0.81) screened by LDCT (pheterogeneity = 0.09). Findings from LUSI are in line with those from other trials, including NLST, that suggest a stronger reduction of lung cancer mortality after LDCT screening among women as compared to men. This heterogeneity could be the result of different relative counts of lung tumor subtypes occurring in men and women.

Growth of the thoracic aorta in the smoking population: The Danish Lung Cancer Screening Trial

BackgroundAlthough the descending aortic diameter is larger in smokers, data about thoracic aortic growth is missing. Our aim is to present the distribution of thoracic aortic growth in smokers and to compare it with literature of the general population. MethodsCurrent and ex-smokers aged 50–70 years from the longitudinal Danish Lung Cancer Screening Trial, were included. Mean and 95th percentile of annual aortic growth of the ascending aortic (AA) and descending aortic (DA) diameters were calculated with the first and last non-contrast computed tomography scans during follow-up. Determinants of change in aortic diameter over time were investigated with linear mixed models. ResultsA total of 1987 participants (56% male, mean age 57.4 ± 4.8 years) were included. During a median follow-up of 48 months, mean AA and DA growth rates were comparable between males (AA 0.12 ± 0.31 mm/year and DA 0.10 ± 0.30 mm/year) and females (AA 0.11 ± 0.29 mm/year and DA 0.13 ± 0.27 mm/year). The 95th percentile ranged from 0.42 to 0.47 mm/year, depending on sex and location. Aortic growth was comparable between current and ex-smokers and aortic growth was not associated with pack-years. Our findings are consistent with aortic growth rates of 0.08 to 0.17 mm/years in the general population. Larger aortic growth was associated with lower age, increased height, absence of medication for hypertension or hypercholesterolemia and lower Agatston scores. ConclusionsThis longitudinal study of smokers in the age range of 50–70 years shows that ascending and descending aortic growth is approximately 0.1 mm/year and is consistent with growth in the general population.

Whom to screen? A view on lung cancer screening from the pneumologist’s perspective

The benefits of screening programs are highly dependent on risk group definition. This is especially true for lung cancer screening. Results from the National Lung Cancer Screening Trial (NLST) and the NELSON trial (Dutch/Belgian randomised lung cancer screening trial) demonstrated that lung cancer screening using low-dose CT scans results in reduction of cancer-related mortality. This article gives a short overview on participant selection in the NLST and NELSON trials, and on current evidence for implementation of multivariable risk prediction models.

Lung cancer screening—the surgeon’s perspective

Results from lung cancer screening trials are promising and show improved survival of lung cancer patients, mainly due to a shift in tumor stages at the time of detection. More lung nodules for histopathologic workup and earlier tumor stages translate into more patients and work load for thoracic surgical units. This article provides a view on lung cancer screening from a thoracic surgeon’s perspective.

Dairy Product Consumption and Prostate Cancer Risk in the US (P05-034-19)

ObjectivesWe prospectively investigated the association between dairy product intake and prostate cancer risk among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. MethodsPre-diagnostic dairy product intake was assessed using a validated food frequency questionnaire. Incident prostate cancer was ascertained by study visits, local cancer registries, or self-reports and only pathologically-verified cases were included in the analysis. In addition to overall prostate cancer, we classified cases by severity (early vs late stage, or low vs high Gleason scores). Using multivariate Cox regression models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of prostate cancer risk with dairy product intake, as total (all dairy products), by fat content (low- or high-fat), or by fermentation methods (fermented or non-fermented). ResultsAmong 49,472 men, 4134 were diagnosed with prostate cancer during an average follow-up period of 11.2 years. The median total dairy product intake was 101 g/1000 Kcal. Total dairy product consumption was not statistically significantly associated with risk of any prostate cancer or stratified by disease severity. The HR (95% CI) comparing the highest with the lowest quartiles of total dairy product intake was 1.05 (0.96–1.15) for overall prostate cancer risk and ranged from 1.00 (0.88–1.14), for risk of prostate cancer with high-Gleason score, to 1.24 (0.93–1.66), for risk of late-stage prostate cancer. The only statistically significant finding in our stratified analyses was a positive association between high-fat dairy product intake and late-stage prostate cancer risk (HR = 1.37, 95% CI = 1.04–1.82, P-trend = 0.02). However, associations with high-fat dairy intake did not differ by stage (P = 0.15), suggesting a chance finding for the positive association with late-stage prostate cancer. ConclusionsThese preliminary findings do not support the previously-reported harmful impact of dairy product consumption on prostate cancer risk among US men. The observed association of high-fat dairy intake with late-stage prostate cancer needs to be confirmed in other studies. Funding SourcesThis study was funded by the Oregon Health & Science University/Oregon State University Cancer Prevention and Control Initiative.

Biomarker panel for early detection of endometrial cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Objective: No early detection test exists for asymptomatic women at average risk for endometrial cancer. We sought to identify early detection biomarkers for endometrial cancer using prediagnostic serum.

“Early impact” of the lung cancer screening in United States population in the SEER Registries.

1569 Background: The Lung Cancer Screening Trial (NLST) demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS), likely due to finding early-stage NSCLC. Our study investigates the impact of the NLST publication in 2011 on the lung cancer outcomes in the general US Population by assessing the incidence rates, ratio of early/late stage, and lung cancer mortality in the years immediately prior to and following this publication. Methods: Rate sessions from the SEER18 database were accessed during the years 2008-2015. We analyzed overall lung cancer incidence and mortality rates. The ratio of early/late stage was obtained by dividing the number of stage I and II cases by the number of stage III and IV diagnosed by year. We investigate changes in level and trend using interrupted time series in STATA12, considering 2011 as the intervention. In addition, we performed a T-test for averages ratios comparing the years 2007-2010 to the years 2012-2015 for the entire lung cancer population and for subgroups by median family, ethnicity, Sex, Age and SEER Registry. Results: Although the overall lung cancer rates remained stable during the study period, a significant increase in the ratio of early/late stage was observed following the release of NLST for the overall lung cancer population (p=0.006) and for the screening age group (p= 0.014). The effects of ratio of early/late stage as noted in the overall group persisted for all patient subgroups, except for patients associated with a median income &lt;$40,000, for those there were white, and for the following regions Detroit Metro, Iowa, Greater and Rural Georgia and Louisiana where no association was found between the release of the NLST changes in the ratios of early detection even more, in some cases there was a decrease in late stage detection. There was no impact on lung cancer mortality in the general lung cancer population or in any patient subgroups. Conclusions: Since the publication of the NLST in 2011, there has been no impact on lung cancer mortality or incidence of lung cancer in the general US population. However, favorable increase in the proportion of early stage lung cancers, depending upon median family income, race and location. We expected a greater impact of lung cancer screening after 2015 since CT-screening for lung cancer was adopted by CMS and other insurances during that year.

Impact of comorbidity and age on treatment choice among men with localized prostate cancer.

e16585 Background: Prostate cancer (PCa) is the most commonly diagnosed cancer among men in the United States. A substantial proportion of PCa patients has at least one comorbidity. Comorbidities have a meaningful impact on cancer treatment choice. The objective of this study was to investigate the effect of comorbidity, as well as age, on treatment choice among men with localized PCa. Methods: From the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, men with localized PCa diagnosed from 1994-2014 were selected (N = 10, 281). Comorbidity score was determined based on a modified Charlson index. Treatment was classified as curative, either radical prostatectomy (RP) or radiation therapy with curative intent (RT), or non-curative (all other modalities). We used multivariate logistic regression to assess the association of treatment choice with age and comorbidity score (including their interaction), controlling for D’Amico risk group, demographics and diagnosis year. Results: About half (48.3%) of patients had comorbidity score ≥ 1. Most men received curative treatment (75.2%); RT (55.2%) was more common than RP (44.8%). The likelihood of curative treatment decreased with increasing age; odds ratios (OR) for curative treatment were 0.63 (95%CI: 0.52-0.76), 0.36 (95%CI: 0.30-0.43) and 0.13 (95%CI: 0.11-0.16) for men aged 65-69, 70-74 and 75+, respectively, compared to men aged 55-64. Men with a comorbidity score of 2+ (OR = 0.84; 95%CI: 0.74-0.96) were less likely to receive curative treatment than men with a score of 0. Within curative treatment, older age was strongly associated with RT. Compared to men aged 55-64 years, men aged 65-69 years (OR = 2.0; 95% CI: 1.72-2.3), 70-74 years (OR = 5.3; 95% CI: 4.5-6.3), and 75+ years (OR = 25.0; 95% CI: 17-33) were more likely to receive RT than RP. Men with a comorbidity score of 1 (OR = 1.16; 95%CI: 1.03-1.30) or 2+ (OR = 1.92; 95%CI: 1.6-2.3) were also more likely to receive RT. The interaction between age and comorbidity score was not significant. Conclusions: In this cohort, age was a strong independent predictor of treatment choice for localized PCa. Although comorbidity was not a strong predictor of curative treatment, it was associated with receipt of RT.