Lung Cancer Screening Trial Research Articles

Vitamin D, melanoma risk, and tumor thickness in PLCO cancer screening trial patients.

The incidence of melanoma is increasing. Other than limiting UV exposure, few factors prevent or reduce the risk of melanoma. The aim of this study is to evaluate the relationship between vitamin D intake and melanoma risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. A secondary data analysis was performed on PLCO data. More than 1,300 participants developed melanoma. Melanoma risk may be increased among men within the highest quartile of vitamin D intake (HR 1.27, 95% CI 0.99, 1.61). Women in the highest quartile of vitamin D intake had a decreased risk of invasive melanoma (HR 0.63, 95% CI 0.41, 0.96). Higher education and being white corresponded with deeper tumors (P < .001). High reported vitamin D intake resulted in an increased risk of melanoma among men. Vitamin D intake yielded a protective effect against invasive melanoma in women.

Psychosocial consequences of false positives in the Danish Lung Cancer CT Screening Trial: a nested matched cohort study

ObjectivesLung cancer CT screening can reduce lung cancer mortality, but high false-positive rates may cause adverse psychosocial consequences. The aim was to analyse the psychosocial consequences of false-positive lung cancer...

Dietary Carbohydrates, Fiber, Whole Grain and the Risk of Lung Cancer: Conclusions from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)

Abstract Objectives Inconsistent findings have been reported on the link between dietary carbohydrates and lung cancer incidence. We comprehensively evaluated the associations of dietary carbohydrates, fibers and their food sources with lung cancer in the PLCO Cancer Screening Trial. Methods The study included 113,096 eligible participants recruited to the PLCO trial. Participants had to have completed baseline and diet history questionnaires. The incidence of lung cancer was acquired through self-report and medical record follow-up. A multivariable logistic model adjusted for confounders was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of dietary carbohydrates, fibers, whole grains, glycemic index (GI) and glycemic load (GL) for lung cancer. Similar methods were applied in analyzing the food sources of carbohydrates and fibers. Multinomial logistic models were used for sensitivity analysis with lung cancer subtypes as outcomes. Results Dietary carbohydrates and GL were associated with a lower risk of lung cancer in the PLCO population. Among various carbohydrates, 30-gram daily consumption of dietary fibers was related to a lower risk of lung cancer (the fourth vs the first quartile OR: 0.62, 95% CI: 0.54–0.72) compared with 8.8-gram. Furthermore, consuming 2.3 servings of whole grain per day as opposed to 0.3 servings per day was associated with a lower risk of lung cancer (OR: 0.73, 95% CI: 0.64–0.83). Nevertheless, a higher risk of lung cancer was seen for high-GI food consumption (P = 0.013) and refined carbohydrates from soft drinks (P = 0.016). Conclusions A higher quantity of high-quality carbohydrates and fibers from fruits, vegetables, and whole grains are associated with lower lung cancer risk. Refined carbohydrates, such as soft drinks, appear to increase risk. Funding Sources The University Postgraduate Fellowship from the University of Hong Kong.

Causal Proportional Hazards Estimation with a Binary Instrumental Variable.

Instrumental variables (IV) are a useful tool for estimating causal effects in the presence of unmeasured confounding. IV methods are well developed for uncensored outcomes, particularly for structural linear equation models, where simple two-stage estimation schemes are available. The extension of these methods to survival settings is challenging, partly because of the nonlinearity of the popular survival regression models and partly because of the complications associated with right censoring or other survival features. Motivated by the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer screening trial, we develop a simple causal hazard ratio estimator in a proportional hazards model with right censored data. The method exploits a special characterization of IV which enables the use of an intuitive inverse weighting scheme that is generally applicable to more complex survival settings with left truncation, competing risks, or recurrent events. We rigorously establish the asymptotic properties of the estimators, and provide plug-in variance estimators. The proposed method can be implemented in standard software, and is evaluated through extensive simulation studies. We apply the proposed IV method to a data set from the Prostate, Lung, Colorectal and Ovarian cancer screening trial to delineate the causal effect of flexible sigmoidoscopy screening on colorectal cancer survival which may be confounded by informative noncompliance with the assigned screening regimen.

Computed tomography screening for lung cancer.

Cigarette smoking is the attributable cause for 90% of lung cancers. To complement preventative strategies, the advent of lung cancer screening programs targeted at prior and active smokers has been explored to reduce the mortality and morbidity of this lethal malignancy. In this article, we discuss the results of major computed tomography-based lung cancer screening trials, cost-effectiveness of screening, guidelines from major societies and future directions of the field.

Dietary intake of broccoli and the risk of cancer in the prostate, lung, colorectal, and ovarian cancer (PCLO) screening trial.

e13560 Background: The cruciferous vegetable broccoli, are a good source of vitamins, minerals and fibre, as well as thiol phytochemicals (indole-3-carbinol), glucosinolates (isothiocyanates, its metabolite, sulforaphane), carotenoids (lutein and zeaxanthin) and flavonols (kaempferol). Laboratory and human biopsy studies have found that broccoli intake influenced epigenetic expression of genes via blockage of histone deacetylase which reduce inflammation and cancer growth. Clinically, a randomised control study reported dried broccoli extract (along with three other foods) influenced PSA progression in men with prostate cancer1. However, no preventative intervention studies in humans have been conducted and data from cohort studies are inconsistent for its influence on cancer incidence2,3. Methods: We analysed 49,104 people within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of any cancer were reported in 8,263 (16.83%) during the 11.5 year follow up. Broccoli consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between broccoli consumption groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between broccoli intake and cancer incidence. Results: Broccoli consumption was associated with reduced cancer incidence: HR 0.95 (CI 0.93-0.97, p &lt; 0.001). This pattern persisted with adjustments for age, sex, race, education level and family history (HR 0.97, CI 0.96-0.99, p = 0.007) as well as smoking, BMI and alcohol consumption (HR 0.98, CI 0.96-0.99, p = 0.010). Conclusions: The study identified an association between increased broccoli consumption and reduced cancer risk. In practical terms, 15g of broccoli, or more, consumed per day (about a small cup) was associated with a 5% lower risk of cancer. Broccoli should continue to be included in healthy eating advice. This data supports the consideration of future prospective intervention studies investigating the role of broccoli as part of a cancer prevention programme.

Dietary consumption of tea and the risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.

e13559 Background: The popular beverage tea, brewed from infused leaves of camellia sinesis, contains non-phytoestrogenic polyphenols such as flavonoids, anthocyanidins, flavanols (epigallocatechin gallate); phenolic acids (ellagic acid) and stimulants (caffeine, theophylline). Laboratory studies report tea promotes antioxidant enzyme formation, slows cancer cell proliferation and unblocks apoptosis. Clinically, the Pomi-T randomised study reported tea extract (along with three other foods) reduced PSA progression in men with prostate cancer1. Evidence of prostate cancer prevention, however, from prospective cohort data is conflicting with one recent study even implying an increased risk2. Methods: We analysed 25,097 men within the intervention arm of the 155,000 participant PLCO screening trial. Histological confirmed cases of prostate cancer were reported in 3,088 men (12.3%) during the 11.5 year follow up. Tea consumption was assessed with a food frequency questionnaire (FFQ). Baseline characteristics were compared between groups using Chi-square and Kruskal-Wallis tests. Cox regression models were used to assess the association between tea intake and prostate cancer incidence. Results: Overall tea consumption was associated with a significantly lower risk of prostate cancer (p = 0.009). More precisely, the participants in the highest third of consumption group had a significantly lower risk compared to those in the lowest third (HR 1.16 (CI 1.05-1.29, p = 0.004). This pattern persisted with adjustments for age, sex, race and education level (p = 0.034), family history of cancer (p = 0.037). Those who never drank tea, however, had no statistical lower risk of prostate cancer compared to other groups (p = 0.501). Conclusions: Among tea drinkers, this data revealed a positive association between drinking tea and a reduced risk of prostate cancer. This data supports the consideration of future prospective intervention studies investigating the role of tea as part of a prostate cancer prevention programme. 1. Thomas et al. The NCRN Pomi-T RCT. Prostate cancer &amp; prostatic diseases (2014), 2,180. 2. Reger et al. Dietary isoflavones and prostate cancer risk. Int J. Cancer (2017), 142; 4, 719.

Total Antioxidant Capacity and Pancreatic Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Total antioxidant capacity (TAC) reflects an individual's overall antioxidant intake. We sought to clarify whether higher TAC is associated with lower risks of pancreatic cancer incidence and mortality in the U.S. general population. A total of 96,018 American adults were identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A ferric-reducing ability of plasma score was used to reflect an individual's TAC intake from diet and/or supplements. Cox regression was used to calculate hazard ratios (HR) for pancreatic cancer incidence, and competing risk regression was used to calculate subdistribution HRs for pancreatic cancer mortality. Restricted cubic spline regression was used to test nonlinearity. A total of 393 pancreatic cancer cases and 353 pancreatic cancer-related deaths were documented. Total (diet + supplements) TAC was found to be inversely associated with pancreatic cancer incidence (HR quartile 4 vs. quartile 1 = 0.53; 95% confidence interval, 0.39-0.72; P trend = 0.0002) and mortality (subdistribution HR quartile 4 vs. quartile 1 = 0.52; 95% confidence interval 0.38-0.72; P trend = 0.0003) in a nonlinear dose-response manner (all P nonlinearity < 0.01). Similar results were observed for dietary TAC. No association of supplemental TAC with pancreatic cancer incidence and mortality was found. In the U.S. general population, dietary but not supplemental TAC level is inversely associated with risks of pancreatic cancer incidence and mortality in a nonlinear dose-response pattern. This is the first prospective study indicating that a diet rich in antioxidants may be beneficial in decreasing pancreatic cancer incidence and mortality.

PCN248 LUNG CANCER SCREENING BY LOW-DOSE COMPUTERISED TOMOGRAPHY: A COST EFFECTIVENESS ANALYSIS OF ALTERNATIVE PROGRAMMES IN THE UNITED KINGDOM USING A NEWLY DEVELOPED NATURAL HISTORY BASED ECONOMIC MODEL

In a systematic review of economic evaluations for lung cancer screening there were no economic models of the UK setting based on disease natural history. This is a well-recognised modelling approach with advantages in modelling population screening, able to explore the cost-effectiveness of multiple alternative potential programme formats. ENaBL is an individual patient simulation model constructed to test lung cancer screening programme designs. It was based on the observed natural history of lung cancer and calibrated against data from the US National Lung Screening Trial. Costs were taken from the UK Lung Cancer Screening Trial. Participants were simulated current or former smokers aged between 55 and 80 years at a higher risk of lung cancer relative to the general population, from which twelve distinct population subgroups were identified. Each were examined in single, triple, annual and biennial arrangements of screening number and interval length, creating 48 distinct screening strategies. These were compared to no screening. The outcome was incremental cost-effectiveness of strategies. Low-dose CT screening is predicted to be effective in bringing forward stage distribution at diagnosis and at reducing lung cancer mortality with decreases ranging from 4.2% to 7.7% relative to no screening, depending on screen frequency. Savings in the cost of treatment from earlier detection are outweighed by costs associated with over-diagnosis, and overall healthcare costs are predicted to increase. Single screen programmes targeted at people with ≥3% predicted lung cancer risk in the age ranges 55 to 75 years, and 60 to 75 years produced ICERs of £28,784 and £28,169 per QALY gained, respectively. Lung cancer screening may not be cost-effective, depending on the cost-effectiveness threshold used. Thresholds of £20,000 to £30,000 per QALY are commonly used in the UK, and screening may be cost-effective with the higher threshold.

Abstract A39: The human oral microbiota and risk of lung cancer: An analysis of three prospective cohort studies

Abstract Background: The oral microbiota may be associated with lung cancer risk through direct mechanisms, including infection, immune responses, and periodontal disease, and through indirect mechanisms such as the modification of the oral microbiota by tobacco. We conducted a case-cohort study nested within three US prospective cohort studies to evaluate the association between oral microbiota ascertained years before a cancer diagnosis and risk of lung cancer. Methods: Incident lung cancer cases within the Agricultural Health Study (AHS; N=244), NIH-AARP Diet and Health Study (N=376), and the Prostate, Lung, Colorectum, and Ovarian Cancer Screening Trial (PLCO; N=700) who provided an oral wash sample were identified. The median time between oral sample collection and diagnosis was approximately 6.6 years, 3.4 years, and 4.5 years for AHS, NIH-AARP, and PLCO, respectively. A referent subcohort was randomly selected by strata of age, sex, and cigarette smoking history. We extracted DNA using the DSP DNA Virus Pathogen kit, and the V4 region of the 16S rRNA gene was PCR amplified and sequenced using the MiSeq. The sequencing data were processed using QIIME2 with the DADA2 plugin and we generated alpha and beta diversity metrics. Cox proportional hazards models were used to evaluate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between the oral microbial measures and the risk of lung cancer with adjustment for known lung cancer risk factors, and estimates from the three cohorts were meta-analyzed. Results: Increased alpha diversity was associated with decreased lung cancer risk, although only the association with the Shannon Index reached statistical significance (HR for 5th quintile versus 1st quintile 0.74; 95% CI 0.60, 0.92) with no evidence of between-study heterogeneity (p = 0.5968). Specific principal coordinate vectors from the beta diversity matrices were also significantly associated with lung cancer risk, suggesting differing bacterial communities between future lung cancer cases. When stratified by histologic subtypes, the inverse association with alpha diversity was restricted to squamous cell carcinoma, with all alpha diversity metrics reaching statistical significance (e.g., Faith’s phylogenetic diversity HR for 5th quintile versus 1st quintile 0.57; 95% CI: 0.37, 0.87). Similarly, when stratified by smoking history, the inverse association with alpha diversity was restricted to former smokers (e.g., observed species HR for 5th quintile versus 1st quintile 0.63; 95% CI: 0.44, 0.89). Conclusions: In oral wash samples collected years before diagnosis, we found significant associations between both alpha and beta diversity metrics of the oral microbial communities and risk of lung cancer. Additional work is required to understand the associations by histologic subtype and smoking history. Citation Format: Emily Vogtmann, Xing Hua, Guoqin Yu, Autumn Hullings, Yunhu Wan, Casey L Dagnall, Kristine Jones, Belynda D. Hicks, Amy Hutchinson, Shalabh Suman, Bin Zhu, Barry Graubard, Mitchell H. Gail, J. Gregory Caporaso, William Wheeler, Dale Sandler, Laura E. Beane Freeman, Linda Liao, Neal D. Freedman, Neil Caporaso, Rashmi Sinha, Jianxin Shi, Christian C Abnet. The human oral microbiota and risk of lung cancer: An analysis of three prospective cohort studies [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A39.

Estimation of the risk of lung cancer in women participating in a population-based breast cancer screening program

IntroductionLung cancer mortality is increasing in women. In Spain, estimates suggest that lung cancer mortality may soon surpass breast cancer mortality, the main cause of cancer mortality among women. The aim of this study was to estimate the proportion of women at high risk of developing lung cancer in a group of participants in a population-based breast cancer screening program. MethodsCross-sectional study in a sample of women who participated in a population-based breast cancer screening program in 2016 in Hospitalet de Llobregat n = 1,601. High risk of lung cancer was defined according to the inclusion criteria of the National Lung Screening Trial (NLST) and the Dutch-Belgian randomized lung cancer screening trial (NELSON). ResultsAround 20% of smokers according to NLST and 40% of smokers according to NELSON criteria, and around 20% of former smokers according to both criteria, are at high risk of developing lung cancer. A positive and statistically significant trend is observed between the proportion of women at high risk and nicotine dependence measured with the brief Fagerström Test. ConclusionsA high proportion of participants in this breast cancer screening program have a high risk of developing lung cancer and would be eligible to participate in a lung cancer screening program. Population-based breast cancer screening programs may be useful to implement lung cancer primary prevention activities.

Chronic Obstructive Pulmonary Disease Quantification Using CT Texture Analysis and Densitometry: Results From the Danish Lung Cancer Screening Trial

OBJECTIVE. The purpose of this study is to establish whether texture analysis and densitometry are complementary quantitative measures of chronic obstructive pulmonary disease (COPD) in a lung cancer screening setting. MATERIALS AND METHODS. This was a retrospective study of data collected prospectively (in 2004-2010) in the Danish Lung Cancer Screening Trial. The texture score, relative area of emphysema, and percentile density were computed for 1915 baseline low-dose lung CT scans and were evaluated, both individually and in combination, for associations with lung function (i.e., forced expiratory volume in 1 second as a percentage of predicted normal [FEV1% predicted]), diagnosis of mild to severe COPD, and prediction of a rapid decline in lung function. Multivariate linear regression models with lung function as the outcome were compared using the likelihood ratio test or the Vuong test, and AUC values for diagnostic and prognostic capabilities were compared using the DeLong test. RESULTS. Texture showed a significantly stronger association with lung function (p < 0.001 vs densitometric measures), a significantly higher diagnostic AUC value (for COPD, 0.696; for Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 1, 0.648; for GOLD grade 2, 0.768; and for GOLD grade 3, 0.944; p < 0.001 vs densitometric measures), and a higher but not significantly different association with lung function decline. In addition, only texture could predict a rapid decline in lung function (AUC value, 0.538; p < 0.05 vs random guessing). The combination of texture and both densitometric measures strengthened the association with lung function and decline in lung function (p < 0.001 and p < 0.05, respectively, vs texture) but did not improve diagnostic or prognostic performance. CONCLUSION. The present study highlights texture as a promising quantitative CT measure of COPD to use alongside, or even instead of, densitometric measures. Moreover, texture may allow early detection of COPD in subjects who undergo lung cancer screening.

Identification of 102 Correlations between Serum Metabolites and Habitual Diet in a Metabolomics Study of the Prostate, Lung, Colorectal, and Ovarian Cancer Trial

Metabolomics has proven useful for detecting objective biomarkers of diet that may help to improve dietary measurement. Studies to date, however, have focused on a relatively narrow set of lipid classes. The aim of this study was to uncover candidate dietary biomarkers by identifying serum metabolites correlated with self-reported diet, particularly metabolites in underinvestigated lipid classes, e.g. triglycerides and plasmalogens. We assessed dietary questionnaire data and serum metabolite correlations from 491 male and female participants aged 55-75 y in an exploratory cross-sectional study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Self-reported intake was categorized into 50 foods, food groups, beverages, and supplements. We examined 522 identified metabolites using 2 metabolomics platforms (Broad Institute and Massachusetts General Hospital). Correlations were identified using partial Pearson's correlations adjusted for age, sex, BMI, smoking status, study site, and total energy intake [Bonferroni-corrected level of 0.05/(50×522) = 1.9×10-6]. We assessed prediction of dietary intake by multiple-metabolite linear models with the use of 10-fold crossvalidation least absolute shrinkage and selection operator (LASSO) regression. Eighteen foods, beverages, and supplements were correlated with ≥1 serum metabolite at the Bonferroni-corrected significance threshold, for a total of 102 correlations. Of these, only 5 have been reported previously, to our knowledge. Our strongest correlations were between citrus and proline betaine (r=0.55), supplements and pantothenic acid (r=0.46), and fish and C40:9phosphatidylcholine (PC) (r=0.35). The multivariate analysis similarly found reasonably large correlations between metabolite profiles and citrus (r=0.59), supplements (r=0.57), and fish (r=0.44). Our study of PLCO participants identified many novel food-metabolite associations and replicated 5 previous associations. These candidate biomarkers of diet may help to complement measures of self-reported diet in nutritional epidemiology studies, though further validation work is still needed.

Risk of Prostate Cancer-related Death Following a Low PSA Level in the PLCO Trial.

Longer-than-annual screening intervals have been suggested to improve the balance of benefits and harms in prostate cancer screening. Many researchers, societies, and guideline committees have suggested that screening intervals could depend on the prostate-specific antigen (PSA) result. We analyzed data from men (N = 33,897) ages 55-74 years with a baseline PSA test in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial (United States, 1993-2001). We estimated 5- and 10-year risks of aggressive cancer (Gleason ≥8 and/or stage III/IV) and 15-year risks of prostate cancer-related mortality for men with baseline PSA ≤ 0.5 ng/mL (N = 4,862), ≤1 ng/mL (N = 15,110), and 1.01-2.5 ng/mL (N = 12,422). A total of 217 men died from prostate cancer through 15 years, although no men with PSA ≤ 1 ng/mL died from prostate cancer within 5 years [95% confidence interval (CI), 0.00%-0.03%]. The 5-year incidence of aggressive disease was low (0.08%; 95% CI, 0.03%-0.12%) for men with PSA ≤ 1 ng/mL, and higher for men with baseline PSA 1.01-2.5 ng/mL (0.51%; 95% CI, 0.38%-0.74%). No men aged ≥65 years with PSA ≤ 0.5 ng/mL died from prostate cancer within 15 years (95% CI, 0.00%-0.32%), and their 10-year incidence of aggressive disease was low (0.25%; 95% CI, 0.00%-0.53%). Compared with white men, black men with PSA ≤ 1 ng/mL had higher 10-year rates of aggressive disease (1.6% vs. 0.4%; P < 0.01). Five-year screening intervals may be appropriate for the 45% of men with PSA ≤ 1 ng/mL. Men ages ≥65 years with PSA ≤ 0.5 ng/mL could consider stopping screening. Substantial risk disparities suggest appropriate screening intervals could depend on race/ethnicity.

Performance of lung cancer screening with low-dose CT in Gejiu, Yunnan: A population-based, screening cohort study.

BackgroundThe performance of lung cancer screening with low‐dose computed tomography (CT) (LDCT) in China is uncertain. This study aimed to evaluate the performance of LDCT lung cancer screening in the Chinese setting.MethodsIn 2014, a screening cohort of lung cancer with LDCT was established in Gejiu, Yunnan Province, a screening center of the Lung Cancer Screening Program in Rural China (LungSPRC). Participants received a baseline screening and four rounds of annual screening with LDCT in two local hospitals until June 2019. We analyzed the rates of participation, detection, early detection, and the clinical characteristics of lung cancer.ResultsA total of 2006 participants had complete baseline screening results with a compliance rate of 98.4%. Of these, 1411 were high‐risk and 558 were nonhigh‐risk participants. During this period, 40 lung cancer cases were confirmed, of these, 35 were screen‐detected, four were post‐screening and one was an interval case. The positive rate of baseline and annual screening was 9.7% and 9.0%, while the lung cancer detection rate was 0.4% and 0.6%, respectively. The proportion of early lung cancer increased from 37.5% in T0 to 75.0% in T4. Adenocarcinoma was the most common histological subtype. Lung cancer incidence according to the criteria of LungSPRC and National Lung Cancer Screening Trial (NLST) was 513.31 and 877.41 per 100 000 person‐years, respectively.ConclusionsThe program of lung cancer screening with LDCT showed a successful performance in Gejiu, Yunnan. However, further studies are warranted to refine a high‐risk population who will benefit most from LDCT screening and reduce the high false positive results.Key pointsThis study reports the results of lung cancer screening with LDCT in Gejiu, Yunnan, a high‐risk area of lung cancer, and it demonstrates that lung cancer screening with LDCT is effective in detecting early‐stage lung cancer. Our program provides an opportunity to explore the performance of LDCT lung cancer screening in the Chinese context.

Increased respiratory morbidity in individuals with interstitial lung abnormalities

BackgroundInterstitial lung abnormalities (ILA) are common in participants of lung cancer screening trials and broad population-based cohorts. They are associated with increased mortality, but less is known about disease specific morbidity and healthcare utilisation in individuals with ILA.MethodsWe included all participants from the screening arm of the Danish Lung Cancer Screening Trial with available baseline CT scan data (n = 1990) in this cohort study. The baseline scan was scored for the presence of ILA and patients were followed for up to 12 years. Data about all hospital admissions, primary healthcare visits and medicine prescriptions were collected from the Danish National Health Registries and used to determine the participants’ disease specific morbidity and healthcare utilisation using Cox proportional hazards models.ResultsThe 332 (16.7%) participants with ILA were more likely to be diagnosed with one of several respiratory diseases, including interstitial lung disease (HR: 4.9, 95% CI: 1.8–13.3, p = 0.008), COPD (HR: 1.7, 95% CI: 1.2–2.3, p = 0.01), pneumonia (HR: 2.0, 95% CI: 1.4–2.7, p < 0.001), lung cancer (HR: 2.7, 95% CI: 1.8–4.0, p < 0.001) and respiratory failure (HR: 1.8, 95% CI: 1.1–3.0, p = 0.03) compared with participants without ILA. These findings were confirmed by increased hospital admission rates with these diagnoses and more frequent prescriptions for inhalation medicine and antibiotics in participants with ILA.ConclusionsIndividuals with ILA are more likely to receive a diagnosis and treatment for several respiratory diseases, including interstitial lung disease, COPD, pneumonia, lung cancer and respiratory failure during long-term follow-up.

Advancement in Low-dose CT Screening for Lung Cancer

米国におけるNLST（National Lung Screening Trial），欧州におけるNELSON（Dutch-Belgian randomized lung cancer screening trial）の2つのランダム化比較試験により，高危険群に対する低線量CT（low-dose computed tomography：LDCT）検診による肺癌死亡減少効果が証明された．NLSTでは胸部X線（chest X-ray：CXR）検診に対する，NELSONでは無検診に対する有用性である．ただし，対照の違いに加え，肺癌死亡減少割合，過剰診断割合は観察期間によって変化するため，2試験の単純な比較は困難である．既に，米国では保険による実施が開始されたが，実用化に際しては問題点も抽出されつつある．今後，日本において実用化するには，非～軽喫煙者に対する有用性評価，検診の実施体制（対策型検診及び任意型検診）の確立に加え，computer-aided diagnosis（CAD），人工知能（artificial intelligence：AI）ならびにバイオマーカー技術等の導入による高効率化と省力化，実施施設，読影医ならびに放射線技師等のインフラ整備とこれらの質の担保が必要となり，このための研究が必要となる．

Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer.

The ketone metabolism pathway is a principle procedure in physiological homeostasis and induces cancer cells to switch between glycolysis and oxidative phosphorylation for energy production. We conducted a two-phase analysis for associations between genetic variants in the ketone metabolism pathway genes and survival of nonsmall cell lung cancer (NSCLC) by analyzing genotyping data from two published genome-wide association studies (GWASs). In the discovery, we used a genotyping dataset from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial in the multivariable Cox proportional hazards regression analysis. We used Bayesian false discovery probability (≤0.80) for multiple testing correction to evaluate associations between 25,819 (2,176 genotyped and 23,643 imputed) single-nucleotide polymorphisms (SNPs) in 162 genes and survival of 1,185 NSCLC patients. Subsequently, we validated the identified significant SNPs with an additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility GWAS study. Finally, we found that three independent and potentially functional SNPs in three different genes (i.e., PLIN2 rs7867814 G>A, SULT2A1 rs2547235 C>T and UGT1A9 rs2011404 C>T) were independently associated with risk of death from NSCLC, with a combined hazards ratio of 1.22 [95% confidence interval = 1.09-1.36 and p = 0.0003], 0.82 (0.74-0.91 and p = 0.0002) and 1.21 (1.10-1.33 and p = 0.0001), respectively. Additional expression quantitative trait loci analysis found that the survival-associated PLIN2 rs7867814 GA + AA genotypes, but not the genotypes of other two SNPs, were significantly associated with increased mRNA expression levels (p = 0.005). These results indicated that PLIN2 variants may be potential predictors of NSCLC survival through regulating the PLIN2 expression.

Magnesium intake and primary liver cancer incidence and mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs. 1 : 0.44; 95% confidence interval: 0.24, 0.80; ptrend = 0.0065) and mortality (subdistribution hazard ratiotertile 3 vs. 1 : 0.37; 95% confidence interval: 0.19, 0.71; ptrend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose-response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all pnonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose-response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.

Tracking the Nonenrolled: Lung Cancer Screening Patterns Among Individuals not Accrued to a Clinical Trial

IntroductionFor lung cancer screening, the available data are often derived from patients enrolled prospectively in clinical trials. We, therefore, investigated lung cancer screening patterns among individuals eligible for, but not enrolled in, a screening trial. Patients and MethodsFrom February 2017 through February 2019, we enrolled subjects in a trial examining telephone-based navigation during low-dose computed tomography (LDCT) for lung cancer screening. We identified patients for whom LDCT was ordered and who were approached, but not enrolled, in the trial. We categorized nonenrollment as the patient had declined or could not be reached. We compared the characteristics and LDCT completion rates among these groups and the enrolled population using the 2-sample t test and χ2 test. ResultsOf 900 individuals approached for participation (mean age, 62 years; 45% women, 53% black), 447 were enrolled in the screening clinical trial. No significant demographic differences were found between the enrolled and nonenrolled cohorts. Of the 453 individuals not enrolled, 251 (55%) had declined participation and 202 (45%) could not be reached, despite up to 6 attempts. LDCT completion was significantly associated with enrollment status: 81% of enrolled individuals, 73% of individuals who declined participation, and 49% of those who could not be reached (P < .001). ConclusionsIn the present single-center study, demographic factors did not predict for participation in a lung cancer screening trial. Lung cancer screening adherence rates were substantially lower for those not enrolled in a screening trial, especially for those who could not be contacted. These findings may inform the broader implementation of screening programs.