Lung Cancer Screening Trial Research Articles

Associations between Two Dietary Quality Scores and Pancreatic Cancer Risk in a US National Prospective Cohort Study

Objective Most previous studies investigated the associations between intake of individual nutrients and risk of disease, which failed to consider the potential interactions and correlations between various nutrients contained in food. Although dietary quality scores provide a comprehensive evaluation of the entire diet, it remains elusive whether they are associated with the risk of pancreatic cancer. Methods Dietary intake data collected with the Dietary Questionnaire (DQX) and Diet History Questionnaire (DHQ) were used to calculate HEI-2015 and DQI-R scores for participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A high score indicates an increased intake of adequacy components and a decreased intake of moderation components. This study included 252 cases of pancreatic cancer documented from 58,477 persons during a median follow-up of 12.2 years in the DQX cohort and 372 cases of pancreatic cancer ascertained from 101,721 persons during a median follow-up of 8.9 years in the DHQ cohort. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between the two dietary quality scores and pancreatic cancer risk. Results After adjustment for confounders, HEI-2015 and DQI-R scores were not significantly associated with pancreatic cancer risk. However, a significantly lower risk was observed for overweight persons with a higher HEI-2015 score in the DQX cohort (HR [95% CI] comparing the highest with lowest tertile: 0.52 [0.32, 0.85], p for trend = 0.009) and those with higher scores of some individual components. Conclusion Collectively, overall dietary quality is not associated with an altered risk of pancreatic cancer in this US population.

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study.

To clarify the inconsistent findings of epidemiological studies on the association between dietary garlic consumption and colorectal cancer (CRC) incidence, by prospectively assessing the association in a large US population. Data of 58,508 participants (aged 55-74) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were analyzed. Dietary data were collected using a validated questionnaire. Multivariable Cox regression analysis determined hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline regression was used to investigate the non-linear relationship, and subgroup analysis was conducted to examine potential effect modifiers. During a median follow-up of 12.05 years, 782 CRC cases were documented, including 456 proximal colon cancer cases, 322 distal CRC cases, and 4 CRC cases with an unknown site. Moderate dietary garlic consumption was significantly associated with a reduced risk of overall CRC (HRquintile 3vs. 1: 0.70, 95% CI: 0.54 to 0.91, p = 0.007, P for trend: 0.434), exhibiting a U-shaped dose-response pattern, and also with overall CRC in males in the stratified Cox regression model (Model 2: HRquintile 3vs. 1: 0.57, 95% CI: 0.40 to 0.81, p = 0.002), but not in females. The protective association was more pronounced in men, Caucasian, and those with lower alcohol consumption. Notably, these protective effects were observed for overall distal CRC (HRquintile 3vs. 1: 0.62, 95% CI: 0.42 to 0.93, p = 0.021; and HRquintile 4vs. 1: 0.63, 95% CI: 0.43 to 0.92, p = 0.018, P for trend: 0.208); and for distal CRC in males (HRquintile 3vs. 1: 0.40, 95% CI: 0.22 to 0.71, p = 0.002, P for trend: 0.696), but not for proximal CRC. Moderate consumption of dietary garlic is associated with a decreased CRC risk in the US population, with variations based on CRC anatomic subsites. Further in-depth prospective studies are needed to validate these findings in different populations and to explore subsites-specific associations.

Deaths averted: An unbiased alternative to rate ratios for measuring the performance of cancer screening programs.

Screening trials and meta-analyses emphasize the ratio of cancer death rates in screening and control arms. However, this measure is diluted by the inclusion of deaths from cancers that only became detectable after the end of active screening. We review traditional analysis of cancer screening trials and show that ratio estimates are inevitably biased to the null, because follow-up (FU) must continue beyond the end of the screening period and thus includes cases only becoming detectable after screening ends. But because such cases are expected to occur in equal numbers in the two arms, calculation of the difference between the number of cancer deaths in the screening and control arms avoids this dilutional bias. This difference can be set against the number of invitations to screening; we illustrate by reanalyzing data from all trials of tomography screening of lung cancer (LC) using this measure. In nine trials of LC screening from 2000 to 2013, a total of 94,441 high-risk patients were invited to be in screening or control groups, with high participation rates (average 95%). In the older trials comparing computed tomography to chest X-ray, 88,285 invitations averted 83 deaths (1068 per death averted (DA)). In the six more recent trials with no screening in the control group, 69,976 invitations averted 121 deaths (577 invitations per DA). Screens per DA is an undiluted measure of screening's effect and it is unperturbed by the arbitrary duration of FU. This estimate can be useful for program planning and informed consent.

Why is the screening rate in lung cancer still low? A seven-country analysis of the factors affecting adoption.

Strong evidence of lung cancer screening's effectiveness in mortality reduction, as demonstrated in the National Lung Screening Trial (NLST) in the US and the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON), has prompted countries to implement formal lung cancer screening programs. However, adoption rates remain largely low. This study aims to understand how lung cancer screening programs are currently performing. It also identifies the barriers and enablers contributing to adoption of lung cancer screening across 10 case study countries: Canada, China, Croatia, Japan, Poland, South Korea and the United States. Adoption rates vary significantly across studied countries. We find five main factors impacting adoption: (1) political prioritization of lung cancer (2) financial incentives/cost sharing and hidden ancillary costs (3) infrastructure to support provision of screening services (4) awareness around lung cancer screening and risk factors and (5) cultural views and stigma around lung cancer. Although these factors have application across the countries, the weighting of each factor on driving or hindering adoption varies by country. The five areas set out by this research should be factored into policy making and implementation to maximize effectiveness and outreach of lung cancer screening programs.

Variable Selection for Length-Biased and Interval-Censored Failure Time Data

Length-biased failure time data occur often in various biomedical fields, including clinical trials, epidemiological cohort studies and genome-wide association studies, and their analyses have been attracting a surge of interest. In practical applications, because one may collect a large number of candidate covariates for the failure event of interest, variable selection becomes a useful tool to identify the important risk factors and enhance the estimation accuracy. In this paper, we consider Cox’s proportional hazards model and develop a penalized variable selection technique with various popular penalty functions for length-biased data, in which the failure event of interest suffers from interval censoring. Specifically, a computationally stable and reliable penalized expectation-maximization algorithm via two-stage data augmentation is developed to overcome the challenge in maximizing the intractable penalized likelihood. We establish the oracle property of the proposed method and present some simulation results, suggesting that the proposed method outperforms the traditional variable selection method based on the conditional likelihood. The proposed method is then applied to a set of real data arising from the Prostate, Lung, Colorectal and Ovarian cancer screening trial. The analysis results show that African Americans and having immediate family members with prostate cancer significantly increase the risk of developing prostate cancer, while having diabetes exhibited a significantly lower risk of developing prostate cancer.

Disclosure of suicidal ideation in non-psychiatric clinical research: Experience using a novel suicide risk management algorithm in a multi-center smoking cessation trial

Background Clinical trials involving pharmacologic or behavioral treatments often assess depression and suicidal ideation for purposes of screening, baseline assessment of potential moderators or mediators of treatment, or as a study outcome, even if the primary condition under study is not a mental health disorder. Suicide risk management in the context of clinical research poses significant clinical, ethical, and practical challenges, and the literature provides little guidance with respect to outcomes of suicide risk management protocols (SRMPs) or suicide risk assessment instruments deployed in the clinical research setting. Methods We report our experience using a novel SRMP in the Program for Lung Cancer Screening and Tobacco Cessation (PLUTO) trial through in-person and remote interactions. Results An SRMP was developed for non-clinical research staff to assess and respond to participants who express suicidal ideation. Between September 2016 and April 2021, the SRMP was used 61 times for 59 individuals. The SRMP was activated by explicit probing of suicidal ideation in 46 of 61 uses (75%). Subject risk was categorized as high-risk in 6 of 61 SRMP uses (10%). Conclusion Our findings demonstrate a useful tool for the management of suicidal ideation and behavior in a clinical trial. Suicidal ideation may be endorsed by only a small number of study participants, however participant safety dictates the need to develop and implement a practical SRMP. These findings may be of relevance to researchers collecting patient reported outcomes remotely. Researchers should consider available resources for SRMPs during design and start-up phases of research.

Absolute lung cancer risk increases among individuals with >15 quit-years: Analyses to inform the update of the American Cancer Society lung cancer screening guidelines.

This report quantifies counteracting effects of quit-years and concomitant aging on lung cancer risk, especially on exceeding 15 quit-years, when the US Preventive Services Task Force (USPSTF) recommends curtailing lung-cancer screening. Cox models were fitted to estimate absolute lung cancer risk among Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) and National Lung Screening Trial (NLST) participants who ever smoked. Absolute lung cancer risk and gainable years of life from screening for individuals aged 50 to 80 in the US-representative National Health Interview Survey (NHIS) 2015-2018 who ever smoked were projected. Relaxing USPSTF recommendations to 20/25/30 quit-years versus augmenting USPSTF criteria with individuals whose estimated gain in life expectancy from screening exceeded 16.2days according to the Life Years From Screening-CT (LYFS-CT) prediction model was compared. Absolute lung cancer risk increased by 8.7%/year (95% CI, 7.7%-9.7%; p<.001) as individuals aged beyond 15 quit-years in the PLCO, with similar results in NHIS and NLST. For example, mean 5-year lung cancer risk for those aged 65 years with 15 quit-years=1.47% (95% CI, 1.35%-1.59%) versus 1.76% (95% CI, 1.62%-1.90%) for those aged 70 years with 20 quit-years in the PLCO. Removing the quit-year criterion would make 4.9 million more people eligible and increase the proportion of preventable lung cancer deaths prevented (sensitivity) from 63.7% to 74.2%. Alternatively, augmentation using LYFS-CT would make 1.7million more people eligible while increasing the lung cancer death sensitivity to 74.0%. Because of aging, absolute lung cancer risk increases beyond 15 quit-years, which does not support exemption from screening or curtailing screening once it has been initiated. Compared with relaxing the USPSTF quit-year criterion, augmentation using LYFS-CT could prevent most of the deaths at substantially superior efficiency, while also preventing deaths among individuals who currently smoke with low intensity or long duration.

MA19.06 Artificial Intelligence as Concurrent Reader in Prospective European Lung Cancer Screening (4-IN-THE-LUNG-RUN) Trial

MA19.06 Artificial Intelligence as Concurrent Reader in Prospective European Lung Cancer Screening (4-IN-THE-LUNG-RUN) Trial

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.

Analysis of genome-wide 5-hydroxymethylation of blood samples stored in different anticoagulants: opportunities for the expansion of clinical resources for epigenetic research

ABSTRACT Background: Elucidating epigenetic mechanisms could provide new biomarkers for disease diagnosis and prognosis. Technological advances allow genome-wide profiling of 5-hydroxymethylcytosines (5hmC) in liquid biopsies. 5hmC-Seal followed by NGS is a highly sensitive technique for 5hmC biomarker discovery in cfDNA. Currently, 5hmC Seal is optimized for EDTA blood collection. We asked whether heparin was compatible with 5hmC Seal as many clinical and biobanked samples are stored in heparin. Methods: We obtained 60 samples in EDTA matched to 60 samples in heparin from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Samples were comprised of 30 controls and 30 individuals who were later diagnosed with colon cancer. We profiled genome-wide 5hmC in cfDNA using 5hmC-Seal assay followed by NGS. The 5hmC profiling data from samples collected in EDTA were systematically compared to those in heparin across various genomic features. Results: cfDNA isolation and library construction appeared comparable in heparin vs. EDTA. Typical genomic distribution patterns of 5hmC, including gene bodies and enhancer markers, were comparable in heparin vs. EDTA. 5hmC analysis of cases and controls yielded highly correlated differential features suggesting that both anticoagulants were compatible with 5hmC Seal assay. Conclusions: While not currently recommended for the 5hmC-Seal protocol, blood samples stored in heparin were successfully used to generate analysable and biologically relevant genome-wide 5hmC profiling. Our findings are the first to support opportunities to expand the biospecimen resource to heparin samples for 5hmC Seal and perhaps other PCR-based technologies in epigenetic research.

Cohort profile: design and methods of the Chinese colorectal, breast, lung, liver, and stomach cancer screening trial (C-BLAST)

Cohort profile: design and methods of the Chinese colorectal, breast, lung, liver, and stomach cancer screening trial (C-BLAST)

Lung-Reporting and Data System 2.0: Impact of the Updated Approach to Juxtapleural Nodules During Lung Cancer Screening Using the National Lung Cancer Screening Trial Data Set.

To determine the frequency of malignancy of nonperifissural juxtapleural nodules (JPNs) measuring 6 to < 10 mm in a subset of low-dose chest computed tomographies from the National Lung Cancer Screening Trial and the rate of down-classification of such nodules in Lung-Reporting and Data System (RADS) 2.0 compared with Lung-RADS 1.1. A secondary analysis of a subset of the National Lung Screening Trial was performed. An exemption was granted by the Institutional Review Board. The dominant noncalcified nodule measuring 6 to <10 mm was identified on all available prevalence computed tomographies. Nodules were categorized as pleural or nonpleural. Benign or malignant morphology was recorded. Initial and updated categories based on Lung-RADS 1.1 and Lung-RADS 2.0 were assigned, respectively. The impact of the down-classification of JPN was assessed. Both classification schemes were compared using the McNemar test ( P < 0.01). A total of 2813 patients (62 ± 5 y, 1717 men) with 4408 noncalcified nodules were studied. One thousand seventy-three dominant nodules measuring 6 to <10 mm were identified. Three hundred forty-eight (32.4%) were JPN. The updated scheme allowed down-classification of 310 JPN from categories 3 (n = 198) and 4A (n = 112) to category 2. We, therefore, estimate a 4.8% rate of down-classification to category 2 in the entire National Lung Screening Trial screening group. Two/348 (0.57%) JPN were malignant, both nonbenign in morphology. The false-positive rate decreased in the updated classification ( P < 0.01). This study demonstrates the low malignant potential of benign morphology JPN measuring 6 mm to <10 mm. The Lung-RADS 2.0 approach to JPN is estimated to reduce short-term follow-ups and false-positive results.

Association of diabetes risk reduction diet with renal cancer risk in 101,755 participants: a prospective study

BackgroundThere is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population.MethodsA population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses.ResultsOver a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose–response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05).ConclusionsOur findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.

Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993–2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, ORcontinuous = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), Ptrend = 0.04; ORcontinuous = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [ORcontinuous = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.

A metabolomic investigation of serum perfluorooctane sulfonate and perfluorooctanoate

BackgroundExposures to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), environmentally persistent chemicals detectable in the blood of most Americans, have been associated with several health outcomes. To offer insight into their possible biologic effects, we evaluated the metabolomic correlates of circulating PFOS and PFOA among 3,647 participants in eight nested case-control serum metabolomic profiling studies from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. MethodsMetabolomic profiling was conducted by Metabolon Inc., using ultra high-performance liquid chromatography/tandem accurate mass spectrometry. We conducted study-specific multivariable linear regression analyses estimating the associations of metabolite levels with levels of PFOS or PFOA. For metabolites measured in at least 3 of 8 nested case-control studies, random effects meta-analysis was used to summarize study-specific results (1,038 metabolites in PFOS analyses and 1,100 in PFOA analyses). ResultsThe meta-analysis identified 51 and 38 metabolites associated with PFOS and PFOA, respectively, at a Bonferroni-corrected significance level (4.8x10-5 and 4.6x10-5, respectively). For both PFOS and PFOA, the most common types of associated metabolites were lipids (sphingolipids, fatty acid metabolites) and xenobiotics (xanthine metabolites, chemicals). Positive associations were commonly observed with lipid metabolites sphingomyelin (d18:1/18:0) (P = 2.0x10-10 and 2.0x10-8, respectively), 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (P = 2.7x10-15, 1.1x10-17), and lignoceroylcarnitine (C24) (P = 2.6x10-8, 6.2x10-6). The strongest positive associations were observed for chemicals 3,5-dichloro-2,6-dihydroxybenzoic acid (P = 3.0x10-112 and 6.8x10-13, respectively) and 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (P = 1.6x10-14, 2.3x10-6). Other metabolites positively associated with PFOS included D-glucose (carbohydrate), carotene diol (vitamin A metabolism), and L-alpha-aminobutyric acid (glutathione metabolism), while uric acid (purine metabolite) was positively associated with PFOA. PFOS associations were consistent even after adjusting for PFOA as a covariate, while PFOA associations were greatly attenuated with PFOS adjustment. ConclusionsIn this large metabolomic study, we observed robust positive associations with PFOS for several molecules. Further investigation of these metabolites may offer insight into PFOS-related biologic effects.

Ultra-Processed Food Consumption and Mortality: Three Cohort Studies in the United States and United Kingdom

Given the increase in ultra-processed food (UPF) consumption, their potential health effects have aroused concern. Whether UPF consumption is associated with cancer and cardiovascular disease mortality is debatable. This study evaluates the association of UPF consumption with mortality. A total of 108,714 U.S. adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (1993-2001), 208,051 UK adults from UK Biobank (2006-2010), and 41,070 U.S. adults from National Health and Nutrition Examination Survey (1999-2018) were included. Dietary data were collected by dietary questionnaire and classified using the NOVA classification. UPF consumption was expressed as the weight proportion of UPFs in total foods consumed. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs. Mediation analysis was used to evaluate whether multiple metabolic pathways mediated the associations in UK Biobank. Analyses were performed in 2022-2023. Combined analyses of the three cohorts showed that those with the highest quartile of UPF consumption had higher risks of all-cause mortality (hazard ratio, 1.16; 95% CI, 1.11-1.20) and cardiovascular disease mortality (hazard ratio, 1.17; 95% CI, 1.06-1.28) compared to the lowest quartile of UPF consumption. UPF consumption was not associated with cancer mortality risk. Biomarkers of liver function have the greatest mediating effects on all-cause mortality (20.3%), and biomarkers of inflammation have the greatest mediating effects on cardiovascular disease mortality (29.2%). Higher UPF consumption was associated with increased all-cause and cardiovascular disease mortality risk, with multiple metabolic pathways playing mediating roles.

Pan-Cancer Analysis of Postdiagnosis Exercise and Mortality.

The impact of postdiagnosis exercise on cause-specific mortality in cancer survivors and whether this differs on the basis of cancer site is unclear. We performed an analysis of 11,480 patients with cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Patients with a confirmed diagnosis of cancer completing a standardized survey quantifying exercise after diagnosis were included. The primary outcome was all-cause mortality (ACM); secondary end points were cancer mortality and mortality from other causes. Cox models were used to estimate the cause-specific hazard ratios (HRs) for ACM, cancer, and noncancer mortality as a function of meeting exercise guidelines versus not meeting guidelines with adjustment for important clinical covariates. After a median follow-up of 16 years from diagnosis, 4,665 deaths were documented (1,940 due to cancer and 2,725 due to other causes). In multivariable analyses, exercise consistent with guidelines was associated with a 25% reduced risk of ACM compared with nonexercise (HR, 0.75; 95% CI, 0.70 to 0.80). Compared with nonexercise, exercise consistent with guidelines was associated with a significant reduction in cancer mortality (HR, 0.79; 95% CI, 0.72 to 0.88) and mortality from other causes (HR, 0.72; 95% CI, 0.66 to 0.78). The inverse relationship between exercise and cause-specific mortality varied by exercise dose. Exercise consistent with guidelines was associated with a reduced hazard of ACM for multiple cancer sites. Reduction in cancer mortality for exercisers was only observed in head and neck and renal cancer. In this pan-cancer sample of long-term cancer survivors, exercise consistent with guidelines was associated with substantial ACM benefit driven by both reductions in cancer and noncancer mortality. The cause-specific impact of exercise differed as a function of cancer site.

Lifetime body weight trajectories and risk of renal cell cancer: a large US prospective cohort study.

Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess bodyweight. Using the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N=138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: 1) BMI at specific ages; 2) adulthood BMI trajectories; 3) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and 4) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC. A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared to individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight (HR:1.49, 95%CI:1.19,1.87), from normal BMI to obesity (HR:2.22, 95%CI:1.70,2.90), and from overweight to obesity (HR:2.78, 95%CI:1.81,4.27). Compared to individuals who were never overweight (WYO=0), elevated HRs were observed among individuals who experienced low (HR:1.31, 95%CI:0.99,1.74), medium (HR:1.57, 95%CI:1.20,2.05), and high (HR:2.10, 95%CI:1.62,2.72) WYO tertile. Weight gain of ≥10kg was associated with increased RCC incidence for each age span. Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk. It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.

Associations between colorectal cancer risk and dietary intake of tomato, tomato products, and lycopene: evidence from a prospective study of 101,680 US adults.

Previous epidemiological studies have yielded inconsistent results regarding the effects of dietary tomato, tomato products, and lycopene on the incidence of colorectal cancer (CRC), possibly due to variations in sample sizes and study designs. The current study used multivariable Cox regression, subgroup analyses, and restricted cubic spline functions to investigate correlations between CRC incidence and mortality and raw tomato, tomato salsa, tomato juice, tomato catsup, and lycopene intake, as well as effect modifiers and nonlinear dose-response relationships in 101,680 US adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. During follow-up 1100 CRC cases and 443 CRC-specific deaths occurred. After adjustment for confounding variables, high consumption of tomato salsa was significantly associated with a reduced risk of CRC incidence (hazard ratio comparing the highest category with the lowest category 0.8, 95% confidence interval 0.65-0.99, p for trend = 0.039), but not with a reduced risk of CRC mortality. Raw tomatoes, tomato juice, tomato catsup, and lycopene consumption were not significantly associated with CRC incidence or CRC mortality. No potential effect modifiers or nonlinear associations were detected, indicating the robustness of the results. In the general US population a higher intake of tomato salsa is associated with a lower CRC incidence, suggesting that tomato salsa consumption has beneficial effects in terms of cancer prevention, but caution is warranted when interpreting these findings. Further prospective studies are needed to evaluate its potential effects in other populations.

An Effective Malignancy Prediction Model for Incidentally Detected Pulmonary Subsolid Nodules Based on Current and Prior CT Scans

IntroductionIt is challenging to diagnose and manage incidentally detected pulmonary subsolid nodules due to their indolent nature and heterogeneity. The objective of this study is to construct a decision tree-based model to predict malignancy of a subsolid nodule based on radiomics features and evolution over time. Materials and MethodsWe derived a training set (2947 subsolid nodules), a test set (280 subsolid nodules) from a cohort of outpatient CT scans, and a second test set (5171 subsolid nodules) from the National Lung Cancer Screening Trial (NLST). A Computer-Aided Diagnosis system (CADs) automatically extracted 28 preselected radiomics features, and we calculated the feature change rates as the change of the quantitative measure per time unit between the prior and current CT scans. We built classification models based on XGBoost and employed 5-fold cross validation to optimize the parameters. ResultsThe model that combined radiomics features with their change rates performed the best. The Areas Under Curve (AUCs) on the outpatient test set and on the NLST test set were 0.977 (95% CI, 0.958-0.996) and 0.955 (95% CI, 0.930-0.980), respectively. The model performed consistently well on subgroups stratified by nodule diameters, solid components, and CT scan intervals. ConclusionThis decision tree-based model trained with the outpatient dataset gives promising predictive performance on the malignancy of pulmonary subsolid nodules. Additionally, it can assist clinicians to deliver more accurate diagnoses and formulate more in-depth follow-up strategies.