Lung Cancer Screening Trial Research Articles

Association Between Diabetes Risk Reduction Diet and Lung Cancer Risk in 98,159 Participants: Results From a Prospective Study.

PurposeTo evaluate the association between diabetes risk reduction diet (DRRD) score and the risk of lung cancer in a large population.MethodsData of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the Cox proportional hazards regression model for the association of DRRD score and lung cancer incidence in all included participants. Prespecified subgroup analyses were performed to evaluate whether the observed association was modified by age, sex, BMI, race/ethnicity, family history of lung cancer, smoking status and history of diabetes.ResultsA total of 98,159 participants were included in this study. The mean (SD) age of the study participants cohort at baseline was 65.5 (5.73) years old. The mean (SD) follow-up time was 8.83 (1.96) years. The mean (SD) score of DRRD was 26.82 (5.19), and ranged from 20.47 (2.3) to 33.65 (2.42) from the lowest quartile to the highest quartile of the DRRD score, inferring the possibility of highest through the lowest risk of type 2 diabetes. The calculated HRs showed there was a trend that higher quartile indicated lower risk of lung cancer after adjusted for covariates (HRQ4vsQ1: 0.85; 95% CI:0.73,0.98; p for trend =0.036). The inverse trend between higher DRRD score and the risk of squamous cell carcinoma was more evident (HRQ4vsQ1: 0.50; 95% CI:0.34,0.73; p for trend =0.002). The inverse association between DRRD score and the incidence of lung cancer was more pronounced in participants who had a clear family history of lung cancer (p for interaction=0.016).ConclusionA protective association between DRRD score and risk of lung cancer is obtained. People are encouraged to adhere to higher DRRD score in their daily diet. Further studies should be conducted to confirm the result and explore the mechanism.

Extending prediction models for use in a new target population with failure time outcomes.

Prediction models are often built and evaluated using data from a population that differs from the target population where model-derived predictions are intended to be used in. In this article, we present methods for evaluating model performance in the target population when some observations are right censored. The methods assume that outcome and covariate data are available from a source population used for model development and covariates, but no outcome data, are available from the target population. We evaluate the finite sample performance of the proposed estimators using simulations and apply the methods to transport a prediction model built using data from a lung cancer screening trial to a nationally representative population of participants eligible for lung cancer screening.

Driving disruption in the solid tumor space: is it time to shift paradigms and develop novel immuno-oncology strategies?

Roisin McGuigan, Editor, Cell & Gene Therapy Insights, speaks to Edward Patz, Chief Executive Officer, Grid Therapeutics, LLC; James and Alice Chen Distinguished Professor of Radiology, Professor in Pharmacology and Cancer Biology, Duke University School of MedicineEdward Patz, Jr is a founder and the CEO of Grid Therapeutics. He is also the James and Alice Chen Distinguished Professor of Radiology and a Professor in Pharmacology and Cancer Biology at Duke University School of Medicine. He began his training in High Energy Physics at Harvard University, received his MD from the University of Maryland, completed his residency and thoracic imaging fellowship at the Brigham and Women’s Hospital and Harvard Medical School, and then was appointed to the faculty in the Department of Radiology at the Brigham, Harvard Medical School, and the Dana Farber Cancer Institute. In 1991, he was recruited to the Thoracic Imaging section in the Department of Radiology at Duke. Dr Patz is a clinician–scientist, with over 200 publications, and has participated in numerous clinical trials including the National Lung Cancer Screening Trial (NLST). For over 25 years, he has been the principal investigator of a basic science laboratory that explores clonal evolution of tumors, biomarkers for early detection, and the role of inflammation in cancer.

Prevalence, symptom burden and under-diagnosis of chronic obstructive pulmonary disease in Polish lung cancer screening population: a cohort observational study

ObjectivesLung cancer screening using low-dose CT may be not effective without considering the presence of comorbidities related to chronic smoking. The aim of the study was to establish the prevalence...

Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids With Incident Colorectal Cancer.

Human studies investigating the prospective relationship between microbial metabolites and colorectal cancer (CRC) risk are lacking. We tested whether higher serum bile acids (BAs) and lower short-chain fatty acids (SCFAs) were associated with CRC risk. In baseline serum collected more than 30 years before a CRC diagnosis, we quantified concentrations of 15 BAs and 6 SCFAs using targeted liquid chromatography with tandem mass spectrometry assays in 1:1 matched cases and controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (men: n = 262 cases; women: n = 233 cases) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (men: n = 598 cases). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for BA and SCFA quartiles and summary measures with CRC overall and by anatomic location using multivariable conditional logistic regression models. PLCO analyses were stratified by sex. All statistical tests were 2-sided. In PLCO women, 7 BAs were strongly associated with increased CRC risk, including the secondary BAs, deoxycholic (ORQ4 v Q1 = 2.85, 95% CI = 1.45 to 5.60, Qtrend = 0.011), glycodeoxycholic (OR Q4 v Q1 = 3.45, 95% CI = 1.79 to 6.64, Qtrend = 0.006), taurodeoxycholic (OR Q4 v Q1 = 2.36, 95% CI = 1.22 to 4.55, Qtrend = 0.023), and glycolithocholic acid (ORQ4 v Q1 = 2.71, 95% CI = 1.41 to 5.22, Qtrend = 0.015). Women in the highest compared with lowest quartile of total SCFAs had a 45% lower risk of CRC (OR = 0.55, 95% CI = 0.31 to 0.98, Ptrend = .03). Associations for total BAs and SCFAs were strongest among women with proximal colon cancer. No statistically significant associations were observed for BA or SCFA measures among men. Serum concentrations of BAs, particularly downstream microbial metabolites of cholic acid, were strongly associated with increased risk of CRC among women.

Prediction of future risk of any and higher-grade prostate cancer based on the PLCO and SELECT trials

BackgroundA model was built that characterized effects of individual factors on five-year prostate cancer (PCa) risk in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This model was validated in a third San Antonio Biomarkers of Risk (SABOR) screening cohort.MethodsA prediction model for 1- to 5-year risk of developing PCa and Gleason > 7 PCa (HG PCa) was built on PLCO and SELECT using the Cox proportional hazards model adjusting for patient baseline characteristics. Random forests and neural networks were compared to Cox proportional hazard survival models, using the trial datasets for model building and the SABOR cohort for model evaluation. The most accurate prediction model is included in an online calculator.ResultsThe respective rates of PCa were 8.9%, 7.2%, and 11.1% in PLCO (n = 31,495), SELECT (n = 35,507), and SABOR (n = 1790) over median follow-up of 11.7, 8.1 and 9.0 years. The Cox model showed higher prostate-specific antigen (PSA), BMI and age, and African American race to be associated with PCa and HGPCa. Five-year risk predictions from the combined SELECT and PLCO model effectively discriminated risk in the SABOR cohort with C-index 0.76 (95% CI [0.72, 0.79]) for PCa, and 0.74 (95% CI [0.65,0.83]) for HGPCa.ConclusionsA 1- to 5-year PCa risk prediction model developed from PLCO and SELECT was validated with SABOR and implemented online. This model can individualize and inform shared screening decisions.

Pearls and Pitfalls in Lung Cancer CT Screening

Annual LDCT lung cancer screening is recommended by the United States Preventive Services Task Force (USPSTF) for high-risk population based on the results from the National Lung Cancer Screening Trial (NLST) that showed a significant (20%) reduction in lung cancer-specific mortality rate with the use of annual low-dose computed tomography (LDCT) screening. More recently, the benefits of lung cancer screening were confirmed by the Dutch- Belgian NELSON trial in Europe. With the implementation of lung screening in large scale, knowledge of the limitations related to false positive, false negative and other potential pitfalls is essential to avoid misdiagnosis. This review outlines the most common potential pitfalls in the characterization of screen-detected lung nodules that include artifacts in LDCT, benign nodules that mimic lung cancer, and causes of false negative evaluations of lung cancer with LDCT and PET/CT studies. Awareness of the spectrum of potential pitfalls in pulmonary nodule detection and characterization, including equivocal or atypical presentations, is important for avoiding misinterpretation that can alter patient management.

Detection of pulmonary nodules with scoutless fixed-dose ultra-low-dose CT: a prospective study.

To determine the accuracy of scoutless, fixed-dose ultra-low-dose (ULD) CT compared to standard-dose (SD) CT for pulmonary nodule detection and semi-automated nodule measurement, across different patient sizes. Sixty-three patients underwent ULD and SD CT. Two readers examined all studies visually and with computer-aided detection (CAD). Nodules detected on SD CT were included in the reference standard by consensus and stratified into 4 categories (nodule category, NODCAT) from the Dutch-Belgian Lung Cancer Screening trial (NELSON). Effects of NODCAT and patient size on nodule detection were determined. For each nodule, volume and diameter were compared between both scans. The reference standard comprised 173 nodules. For both readers, detection rates on ULD versus SD CT were not significantly different for NODCAT 3 and 4 nodules > 50mm3 (reader 1: 93% versus 89% (p = 0.257); reader 2: 96% versus 98% (p = 0.317)). For NODCAT 1 and 2 nodules < 50mm3, detection rates on ULD versus SD CT dropped significantly (reader 1: 66% versus 80% (p = 0.023); reader 2: 77% versus 87% (p = 0.039)). Body mass index and chest circumference did not influence nodule detectability (p = 0.229 and p = 0.362, respectively). Calculated volumes and diameters were smaller on ULD CT (p < 0.0001), without altering NODCAT (84% agreement). Scoutless ULD CT reliably detects solid lung nodules with a clinically relevant volume (> 50mm3) in lung cancer screening, irrespective of patient size. Since detection rates were lower compared to SD CT for nodules < 50mm3, its use for lung metastasis detection should be considered on a case-by-case basis. • Detection rates of pulmonary nodules > 50mm3are not significantly different between scoutless ULD and SD CT (i.e. volumes clinically relevant in lung cancer screening based on the NELSON trial), but were different for the detection of nodules < 50mm3(i.e. volumes still potentially relevant in lung metastasis screening). • Calculated nodule volumes were on average 0.03mL or 9% smaller on ULD CT, which is below the 20-25% interscan variability previously reported with software-based volumetry. • Even though a scoutless, fixed-dose ULD CT protocol was used (CTDIvol0.15mGy), pulmonary nodule detection was not influenced by patient size.

Prediagnostic Serum Vitamin D, Vitamin D Binding Protein Isoforms, and Cancer Survival.

Higher circulating vitamin D has been associated with improved overall cancer survival, but data for organ-specific cancers are mixed. We examined the association between prediagnostic serum 25-hydroxyvitamin D [25(OH)D], the recognized biomarker of vitamin D status, and cancer survival in 4038 men and women diagnosed with 1 of 11 malignancies during 22 years of follow-up (median = 15.6 years) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multivariable-adjusted proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between baseline 25(OH)D concentration and subsequent cancer survival; we also stratified on the common vitamin D binding protein isoforms (Gc1f, Gc1s, and Gc2) defined by two single-nucleotide polymorphisms (rs7041 and rs4588) in the vitamin D binding protein gene GC. All P values were 2-sided. Higher 25(OH)D concentrations were associated with greater overall cancer survival (HR for cancer mortality = 0.83, 95% CI = 0.70 to 0.98 for highest vs lowest quintile; Ptrend = .05) and lung cancer survival (HR = 0.63, 95% CI = 0.44 to 0.90; Ptrend = .03). These associations were limited to cases expressing the Gc2 isoform (HR = 0.38 for Gc2-2, 95% CI = 0.14 to 1.05 for highest vs lowest quintile; Ptrend = .02; and HR = 0.30 for Gc1-2/Gc2-2 combined, 95% CI = 0.16 to 0.56; Ptrend < .001 for overall and lung cancer, respectively). Higher circulating 25(OH)D was associated with improved overall and lung cancer survival. As this was especially evident among cases with the genetically determined Gc2 isoform of vitamin D binding protein, such individuals may gain a cancer survival advantage by maintaining higher 25(OH)D blood concentrations.

Challenges of Implementing Lung Cancer Screening in a Developing Country: Results of the Second Brazilian Early Lung Cancer Screening Trial (BRELT2).

PURPOSEThis paper aims to present the results of a series of several Brazilian institutions that have been carrying out lung cancer screening (LCS).MATERIALS AND METHODSThis is a retrospective, cohort study, with follow-up of individuals of both sexes, with a heavy smoking history, who participated in LCS programs between December 2013 and January 2021 in six Brazilian institutions located in the states of São Paulo, Rio Grande do Sul, and Bahia.RESULTSThree thousand four hundred seventy individuals were included, of which 59.8% were male (n = 2,074) and 50.6% were current smokers (n = 1,758), with 60.7 years (standard deviation 8.8 years). Lung-RADS 4 was observed in 233 (6.7%) patients. Biopsy was indicated by minimally invasive methods in 122 patients (3.5%). Two patients who demonstrated false-negative biopsies and lung cancer were diagnosed in follow-up. Diagnosis of lung cancer was observed in 74 patients (prevalence rate of 2.1%), with 52 (70.3%) in stage I or II. Granulomatous disease was found in 20 patients. There were no statistical differences in the incidence of lung cancer, biopsies, granulomatous disease, and Lung-RADS 4 nodules between public and private patients.CONCLUSIONThere are still many challenges and obstacles in the implementation of LCS in developing countries; however, our multi-institutional data were possible to obtain satisfactory results in these scenarios and to achieve similar results to the main international studies. Granulomatous diseases did not increase the number of lung biopsies. The authors hope that it could stimulate the creation of organized screening programs in regions still endemic for tuberculosis and other granulomatous diseases.

Volumetric Measurements in Lung Cancer Screening Reduces Unnecessary Low-Dose Computed Tomography Scans: Results from a Single-Center Prospective Trial on 4119 Subjects.

This study aims to compare the low-dose computed tomography (LDCT) outcome and volume-doubling time (VDT) derived from the measured volume (MV) and estimated volume (EV) of pulmonary nodules (PNs) detected in a single-center lung cancer screening trial. MV, EV and VDT were obtained for prevalent pulmonary nodules detected at the baseline round of the bioMILD trial. The LDCT outcome (based on bioMILD thresholds) and VDT categories were simulated on PN- and screenee-based analyses. A weighted Cohen’s kappa test was used to assess the agreement between diagnostic categories as per MV and EV, and 1583 screenees displayed 2715 pulmonary nodules. In the PN-based analysis, 40.1% PNs were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.49) and fair (κ = 0.37) for the LDCT outcome and VDT categories, respectively. In the screenee-based analysis, 46% pulmonary nodules were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.52) and fair (κ = 0.34) for the LDCT outcome and VDT categories, respectively. Within a simulated lung cancer screening based on a recommendation by estimated volumetry, the number of LDCTs performed for the evaluation of pulmonary nodules was higher compared with in prospective volumetric management.

Comparison Between the 2021 USPSTF Lung Cancer Screening Criteria and Other Lung Cancer Screening Criteria for Racial Disparity in Eligibility

In 2021, the US Preventive Services Task Force (USPSTF) broadened its age and smoking pack-year requirement for lung cancer screening. To compare the 2021 USPSTF lung cancer screening criteria with other lung cancer screening criteria and evaluate whether the sensitivity and specificity of these criteria differ by race. This study included 912 patients with lung cancer and 1457 controls without lung cancer enrolled in an epidemiology study (INHALE [Inflammation, Health, Ancestry, and Lung Epidemiology]) in the Detroit metropolitan area between May 15, 2012, and March 31, 2018. Patients with lung cancer and controls were 21 to 89 years of age; patients with lung cancer who were never smokers and controls who were never smokers were not included in these analyses. Statistical analysis was performed from August 31, 2020, to April 13, 2021. The study assessed whether patients with lung cancer and controls would have qualified for lung cancer screening using the 2013 USPSTF, 2021 USPSTF, and 2012 modification of the model from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCOm2012) screening criteria. Sensitivity was defined as the percentage of patients with lung cancer who qualified for screening, while specificity was defined as the percentage of controls who did not qualify for lung cancer screening. Participants included 912 patients with a lung cancer diagnosis (493 women [54%]; mean [SD] age, 63.7 [9.5] years) and 1457 control participants without lung cancer at enrollment (795 women [55%]; mean [SD] age, 60.4 [9.6] years). With the use of 2021 USPSTF criteria, 590 patients with lung cancer (65%) were eligible for screening compared with 619 patients (68%) per the PLCOm2012 criteria and 445 patients (49%) per the 2013 USPSTF criteria. With the use of 2013 USPSTF criteria, significantly more White patients than African American patients with lung cancer (324 of 625 [52%] vs 121 of 287 [42%]) would have been eligible for screening. This racial disparity was absent when using 2021 USPSTF criteria (408 of 625 [65%] White patients vs 182 of 287 [63%] African American patients) and PLCOm2012 criteria (427 of 625 [68%] White patients vs 192 of 287 [67%] African American patients). The 2013 USPSTF criteria excluded 950 control participants (65%), while the PLCOm2012 criteria excluded 843 control participants (58%), and the 2021 USPSTF criteria excluded 709 control participants (49%). The 2013 USPSTF criteria excluded fewer White control participants than African American control participants (514 of 838 [61%] vs 436 of 619 [70%]). This racial disparity is again absent when using 2021 USPSTF criteria (401 of 838 [48%] White patients vs 308 of 619 [50%] African American patients) and PLCOm2012 guidelines (475 of 838 [57%] White patients vs 368 of 619 [60%] African American patients). This study suggests that the USPSTF 2021 guideline changes improve on earlier, fixed screening criteria for lung cancer, broadening eligibility and reducing the racial disparity in access to screening.

European lung cancer screening: valuable trial evidence for optimal practice implementation.

Lung cancer screening (LCS) by low-dose computed tomography is a strategy for secondary prevention of lung cancer. In the last two decades, LCS trials showed several options to practice secondary prevention in association with primary prevention, however, the translation from trial to practice is everything but simple. In 2020, the European Society of Radiology and European Respiratory Society published their joint statement paper on LCS. This commentary aims to provide the readership with detailed description about hurdles and potential solutions that could be encountered in the practice of LCS.

Weight Change and Incident Distal Colorectal Adenoma Risk in the PLCO Cancer Screening Trial.

BackgroundAlthough obesity is a known risk factor, the impact of weight change on colorectal adenoma risk is less clear and could have important implications in disease prevention. We prospectively evaluated weight change in adulthood and incident colorectal adenoma.MethodsWe assessed weight change during early-late (age 20 years to baseline, ie, ages 55-74 years), early-middle (20-50 years), and middle-late (50 years-baseline) adulthood using self-reported weight data in relation to incident distal adenoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (cases = 1053; controls = 16 576). For each period, we defined stable weight as greater than −0.5 kg to less than or equal to 1 kg/5 years, weight loss as less than or equal to −0.5 kg/5 years, and weight gain as greater than 1-2, greater than 2-3, or greater than 3 kg/5 years. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression; all tests were 2-sided.ResultsCompared with stable weight, weight loss during early-late adulthood was associated with reduced adenoma risk (OR = 0.54, 95% CI = 0.34 to 0.86), particularly among those who were overweight or obese at age 20 years (OR = 0.39, 95% CI = 0.18 to 0.84). Results were similar for early-middle adulthood but less pronounced for middle-late adulthood. Weight gain greater than 3 kg/5 years during early-late adulthood was associated with increased risk (OR = 1.30, 95% CI = 1.07 to 1.58, Ptrend < .001). Findings appeared stronger among men (OR for >3 kg/5 years = 1.41, 95% CI = 1.11 to 1.80) than women (OR = 1.09, 95% CI = 0.79 to 1.50, Pinteraction = .21).ConclusionsWeight loss in adulthood was associated with reduced adenoma risk, particularly for those who were overweight or obese, whereas weight gain greater than 3 kg/5 years increased risk. Findings underscore the importance of healthy weight maintenance throughout adulthood in preventing colorectal adenoma.

Patterns of finasteride and dutasteride use in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial cohort: effects of socio-demographic factors and a black box warning

Background: Five-alpha reductase inhibitors (5-ARIs), specifically finasteride and dutasteride, have been shown to significantly reduce prostate cancer incidence. However, these agents were also associated with a significant increase in the detection of high-grade prostate cancer leading to an FDA black box warning in 2011. Little is known about the effect of this warning on the subsequent use of these 5-ARIs. The purpose of this analysis was to assess use patterns of finasteride and dutasteride before and after the black box warning. Methods: This cohort study evaluated men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial who had ≥12 months of Medicare Part D coverage from 2008 to 2015, and had not been diagnosed with prostate cancer through 2007. Socio-demographic factors and benign prostatic hyperplasia (BPH) status were ascertained from follow-up questionnaires, while medication use was ascertained from linkage to Medicare Part D claims data. Results: Of 14,833 eligible men, 88.7% identified as non-Hispanic white, 1.7% as African-American, 5.2% as Asian/Pacific Islander and 1.7% as Hispanic. The median age was 72 years; 41.8% reported a BPH diagnosis. Only 13.6% and 4% of the population took finasteride or dutasteride, respectively, at any time from 2008 to 2015. During this period, finasteride use significantly increased from 3.6% to 9.7% and was highest among men with BPH; dutasteride use remained low and decreased from 2.8% to 1.9%. Conclusions: Finasteride use significantly increased after the FDA’s 2011 black box warning, while dutasteride use remained low and steady throughout the study period.

Association between soft drink consumption types and risk of lung cancer and all-cancer: A prospective study of PLCO data.

Diet/sugar-free soft drinks are considered to be healthier than regular soft drinks. However, few studies have examined the relationship between the types of soft drinks (regular and diet/sugar-free) and lung cancer (LC)/all-cancer (AC) risk. In this study, we comprehensively assessed the influence of the type of soft drink consumption on LC/AC risk based on the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Multivariable Cox proportional hazards and competing risks Fine-Gray regression models adjusted for relevant confounders were used to estimate hazard ratios (HRs) and subdistribution HRs for different types of soft drink consumption. In the PLCO population, female subgroup, and the ever/current smoker subgroup, consumption of both regular and diet soft drinks was associated with a significantly reduced risk of LC compared with no soft drinks at all. For the non-lung cancer (NLC) risk, consumption of only diet soft drinks had a significant positive association for the total population and female subgroup. Based on our findings, it was suggested that partial replacement of regular soft drinks with diet soft drinks might be beneficial to LC prevention, especially for females and ever/current smokers. Additionally, completely replacing regular soft drinks with diet soft drinks might be detrimental to NLC prevention, especially for females.

Abstract PO-192: Comparing the association of self-reported race-ethnicity and genetic ancestry with all-cause mortality: A pan-cancer survivor analysis in the PLCO Screening Trial

Abstract Despite improvements in overall cancer survival, there are racial and ethnic disparities in mortality rates among cancer survivors. Further investigation of both socioeconomic factors and genetic ancestry is needed to better understand contributors to disparities in cancer mortality. The aim of this study was to compare self-identified race-ethnicity (SIRE) with genetic ancestry as predictors of all-cause mortality among cancer survivors enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Multivariable Cox-proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality and to assess the effect of SIRE (non-Hispanic White [NHW], non-Hispanic Black [NHB], Asian &amp; Pacific Islander [API], Native Indian [NI], and Hispanic) and genetic ancestry (continuous percentages of African, Asian, and European ancestry summing to 1, obtained from genotype array data and SNP weights) among all cancer survivors and by primary cancer site (&amp;gt;350 survivors). Models were (1) age-adjusted and (2) fully adjusted for: age at cancer diagnosis, year of cancer diagnosis, sex, stage, study arm, education, income, occupation, and percent urbanicity. Likelihood-ratio tests (LRT) were used to independently assess the effect of SIRE or genetic ancestry on overall survival. Participants were followed from cancer diagnosis and censored at first occurrence of death, last contact, or December 31, 2017. Among 27,249 cancer survivors, mean age was 71 years (SD 7.1), and mean follow-up time was 7.1 years (SD 6.1). SIRE and genetic ancestry were both predictors of all-cause mortality in age-adjusted models for all cancer survivors (p-LRT&amp;lt;0.001), and by prostate, colorectal, ovarian, and breast cancers. In the fully adjusted model, SIRE remained significant overall (p-LRT&amp;lt;0.001) and for prostate cancer survivors (p-LRT=0.005). Compared to NHW, API had a lower mortality (HR: 0.76, CI: 0.68-0.84) overall, which was similar for prostate cancer survivors. In comparison, genetic ancestry within the fully adjusted model remained a significant predictor overall (p-LRT&amp;lt;0.001), and for prostate (p-LRT=0.008), colorectal (p-LRT=0.017), and breast cancer survivors (p-LRT=0.014). Compared to European ancestry, African ancestry had an elevated mortality (HR: 1.11, CI: 1.004-1.23) overall but not significant by cancer site. Asian ancestry had a lower mortality (HR: 0.74, CI: 0.66-0.82) overall, as well as for prostate, breast, and colorectal cancer survivors when compared to European ancestry. Our analyses indicate both SIRE and genetic ancestry are important albeit different predictors of all-cause mortality among cancer survivors, with SIRE representing a social construct and genetic ancestry representing a measure of biological variation. Lack of treatment data on all participants was a limitation for this study, and future studies should consider examining disparities by treatment access. Selection of SIRE or genetic ancestry should be carefully considered when evaluating disparities in mortality. Citation Format: Derek W. Brown, Jacqueline B Vo, Ian D. Buller, Naoise C. Synnott, Rena R. Jones, Maria Teresa Landi, Wen-Yi Huang, Mitchell J. Machiela, Amy Berrington de Gonzalez, Neal D. Freedman. Comparing the association of self-reported race-ethnicity and genetic ancestry with all-cause mortality: A pan-cancer survivor analysis in the PLCO Screening Trial [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-192.

Association of genetic variants in autophagy-lysosome pathway genes with susceptibility and survival to prostate cancer.

Previous studies have indicated the connections between autophagy-lysosome pathway genes dysfunction and prostate cancer, but few studies have investigated whether single nucleotide polymorphisms (SNPs) in autophagy-lysosome pathway genes are implicated in prostate cancer risk and survival. Logistic regression analysis and stepwise Cox regression analysis were conducted in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The false positive rate probability (FPRP) method was applied to correct for multiple comparisons. Gene-based analysis was calculated by versatile gene-based association study approach. We found that SLC11A1 rs7573065 significantly increased the risk of prostate cancer [adjusted odds ratio (OR)=1.24, 95% confidence interval (CI)=1.06-1.46, P=7.02×10-3, FPRP=0.082]. Furthermore, rs7573065 was confirmed as the independent predicator of overall survival (OS) for prostate cancer patients [Hazard ratio (HR)=1.30, 95% CI=1.01-1.66, P=0.041]. The significant association between SLC11A1 and prostate cancer risk was calculated by gene-based analysis (P=0.030). We also observed that the mRNA of SLC11A1 in prostate tumor tissues was significantly over-expressed than that in normal tissues. This study suggested that rs7573065 in SLC11A1 was associated with an increased risk and poor OS of prostate cancer. Our findings may provide evidence for genetic variants in autophagy-lysosome pathway as the risk and prognostic biomarkers for prostate cancer.

Inflammatory markers in women with reported benign gynecologic pathology: an analysis of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Associations between benign gynecologic pathologies and circulating inflammatory markers are unknown. Our goal was to evaluate self-reported history of benign gynecologic pathology and subsequent alterations in systemic inflammation. Using nested case-control studies from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, study-specific associations between self-reported history of benign ovarian cysts, uterine fibroids, and endometriosis with inflammatory marker concentrations were evaluated using logistic regression and combined using meta-analysis. Inflammatory markers associated with individual benign pathologies were mutually adjusted for one another to evaluate independent associations. Compared to women without a self-reported history of the pathology evaluated, benign ovarian cysts were associated with increased PAI-1 (OR [95% CI] 6.24 [2.53-15.39], P <.001) and TGF-β1 (3.79 [1.62-8.86], P =.002) and decreased BCA-1 (0.38 [0.19-0.73], P =.004). Uterine fibroids were associated with decreased CXCL11 (0.37 [0.22-0.63], P <.001) and VEGFR3 (0.40 [0.24-0.65], P <.001). Endometriosis was associated with increased SIL-4R (4.75 [1.84-12.26], P =.001). Self-reported history of benign gynecologic pathologies were associated with alterations in inflammatory markers that have been previously linked to cancer risk. Understanding interactions between benign gynecologic pathologies and the systemic immune system may help inform disease risk later in life.

Impact of the National Lung Screening Trial (NLST) publication and Medicare Lung cancer screening payment on lung cancer incidence rates: An interrupted time series analysis

IntroductionExplore the impact of the Lung Cancer Screening Trial (NLST-September-2011) and the Medicare approval for CT-screening (CT-LCS-AP-February-2015) on lung cancer incidence rates, mortality, and the percentage of early-stage lung cancer diagnosis (ESLCD-T1-T2N0M0). MethodsRetrospective interrupted time series analysis using SEER-18 database. All individuals with lung cancer (LC) diagnosis from 2006 to 2016 were included. The effect of NLST and CT-AP-2015 on the monthly percentage of early-stage ESLCD was the primary outcome, additionally LC incidence and mortality rates were calculated. The analysis was performed by age, sex, race, marital status, insurance status, and household income. Bivariate and multivariate models were used to identify predictors of ESLCD. ResultsThe study cohort was composed by 388,207 individuals, 69 years old in average, 46.6 % female, and 81.1 % white. LC incidence and mortality rates declined from 2006 to 2016 without association with NLST-September-2011 and CT-LCS-AP-February-2015. The percentage of ESLCD increased over time for all groups. Overall rates of ESLCD started at 18 % in January-2006 and increased to 25 % by December-2016. The intervention NLST-2011 did not show an impact in the ESLCD while the CT-AP-2015 showed a significant impact in the ESLCD trend (p < 0.001). ESLCD was associated with female, white, insurance, and household incomes above median. Medicare expansion was a significant factor for insured group, married patients and those from households under the median income level. ConclusionMedicare approval for CT screening was found to have a statistically significant effect on the diagnosis of early-stage lung cancer and neither NLST-September-2011 nor CT-AP-2015-February-2015 impacted the incidence nor mortality rates. Policy summaryTo improve early-stage lung cancer diagnosis, it is vital to invest in health policies to increase Lung Cancer Screening implementation and to reduce disparities in access to diagnosis. Furthermore, policies that facilitate access to diagnosis and treatment are crucial to reduce lung cancer mortality.