Lung Cancer-specific Mortality Research Articles

Racialized economic segregation and treatment and outcomes of small-cell lung cancer.

The overall and race-specific associations between racialized economic segregation and all-cause mortality in non-Hispanic White and non-Hispanic Black patients with small-cell lung cancer. We used the Surveillance, Epidemiology, and End Results database to identify men and women diagnosed with SCLC from January 2007 to December 2015 (n=38,393). An Index of Concentration at the Extremes (ICE) was computed to measure county-level racialized economic segregation and categorized into quartile 1 (most privileged: highest concentration of high-income NHW residents) through quartile 4 (least privileged: highest concentration of low-income NHB residents). Multilevel logistic regression was used to estimate odds ratios (ORs) for extensive-stage diagnosis and non-adherence to guideline-recommended treatment. Hazard ratios (HRs) for lung cancer-specific and overall mortality were computed using multilevel Cox regression. Patients in the least privileged counties had higher risks of non-adherence to guideline-recommended treatment (OR=1.23, 95% CI 1.08-1.40; Ptrend <0.01), lung cancer-specific (HR=1.08, 95% CI 1.04-1.12; Ptrend <0.01) and all-cause mortalities (HR=1.13, 95% CI 1.09-1.17; Ptrend <0.0001) compared with patients in the most privileged counties. Adjustment for treatment did not significantly reduce the association with mortality. These associations were comparable between NHB and NHW patients. Segregation was not significantly associated with extensive-stage diagnosis. The results suggest that living in the neighborhoods with higher proportions of low-income households and Black residents had adverse impacts on stage-appropriate treatment and survival of SCLC. This highlights the need for improving access to quality lung cancer care in the less privileged neighborhoods.

Progress against lung cancer, Denmark, 2008-2022.

There has been marked progress against lung cancer in Denmark. To gain further insight into the different aspects of the improvement, we examined the stage-specific incidence rates, stage-specific survival and mortality rates. We used information from the Danish Lung Cancer Registry on date of diagnosis and clinical stage to calculate age-standardised incidence rates and patient survival by sex, period and stage. Information about age-standardised lung cancer-specific mortality rates by sex and period was extracted from The Danish Health Data Authority. Firstly, the decrease in incidence rates was due to a reduction in the rates of advanced stages. Secondly, there was a gradual increase in survival across all stages, and thirdly, the mortality rates gradually decreased over time. The improvements in survival and mortality from lung cancer were due to decreasing incidence rates of advanced cancer and improvement in survival at all stages of the disease.

Patient Lung Cancer Screening Decisions and Environmental and Psychosocial Factors

Screening for lung cancer using low-dose computed tomography is associated with reduced lung cancer-specific mortality, but uptake is low in the US; understanding how patients make decisions to engage with lung cancer screening is critical for increasing uptake. Prior research has focused on individual-level psychosocial factors, but environmental factors (eg, historical contexts that include experiencing racism) and modifying factors-those that can be changed to make it easier or harder to undergo screening-also likely affect screening decisions. To investigate environmental, psychosocial, and modifying factors influencing lung cancer screening decision-making and develop a conceptual framework depicting relationships between these factors. This multimethod qualitative study was conducted from December 2021 to June 2022 using virtual semistructured interviews and 4 focus groups (3-4 participants per group). All participants met US Preventive Services Task Force eligibility criteria for lung cancer screening (ie, age 50-80 years, at least a 20 pack-year smoking history, and either currently smoke or quit within the past 15 years). Screening-eligible US participants were recruited using an online panel. Key factors influencing screening decisions (eg, knowledge, beliefs, barriers, and facilitators) were the main outcome. A theory-informed, iterative inductive-deductive approach was applied to analyze data and develop a conceptual framework summarizing results. Among 34 total participants (interviews, 20 [59%]; focus groups, 14 [41%]), mean (SD) age was 59.1 (4.8) years and 20 (59%) identified as female. Half had a household income below $20 000 (17 [50%]). Participants emphasized historical and present-day racism as critical factors contributing to mistrust of health care practitioners and avoidance of medical procedures like screening. Participants reported that other factors, such as public transportation availability, also influenced decisions. Additionally, participants described psychosocial processes involved in decisions, such as perceived screening benefits, lung cancer risk appraisal, and fear of a cancer diagnosis or harmful encounters with practitioners. In addition, participants identified modifying factors (eg, insurance coverage) that could make receiving screening easier or harder. In this qualitative study of patient lung cancer screening decisions, environmental, psychosocial, and modifying factors influenced screening decisions. The findings suggest that systems-level interventions, such as those that help practitioners understand and discuss patients' prior negative health care experiences, are needed to promote effective screening decision-making.

Cell-free DNA assay for malignancy classification of high-risk lung nodules

ObjectiveAlthough low-dose computed tomography has been proven effective to reduce lung cancer–specific mortality, a considerable proportion of surgically resected high-risk lung nodules were still confirmed pathologically benign. There is an unmet need of a novel method for malignancy classification in lung nodules. MethodsWe recruited 307 patients with high-risk lung nodules who underwent curative surgery, and 247 and 60 cases were pathologically confirmed malignant and benign lung lesions, respectively. Plasma samples from each patient were collected before surgery and performed low-depth (5×) whole-genome sequencing. We extracted cell-free DNA characteristics and determined radiomic features. We built models to classify the malignancy using our data and further validated models with 2 independent lung nodule cohorts. ResultsOur models using one type of profile were able to distinguish lung cancer and benign lung nodules at an area under the curve metrics of 0.69 to 0.91 in the study cohort. Integrating all the 5 base models using cell-free DNA profiles, the cell-free DNA–based ensemble model achieved an area under the curve of 0.95 (95% CI, 0.92-0.97) in the study cohort and 0.98 (95% CI, 0.96-1.00) in the validation cohort. At a specificity of 95.0%, the sensitivity reached 80.0% in the study cohort. With the same threshold, the specificity and sensitivity had similar performances in both validation cohorts. Furthermore, the performance of area under the curve reached 0.97 in both the study and validation cohorts when considering the radiomic profile. ConclusionsThe cell-free DNA profiles-based method is an efficient noninvasive tool to distinguish malignancies and high-risk but pathologically benign lung nodules.

Abstract 4831: Racialized economic segregation and disparities in late-stage diagnosis, treatment and mortality among patients with non-small cell lung cancer

Abstract Importance: Little is known about the impact of residential segregation on early detection, treatment, and prognosis among patients with non-small cell lung cancer (NSCLC), a predominant type of lung cancers. Objective: To examine the associations of racialized economic segregation with the risks of late-stage diagnosis, non-adherence to guideline-recommended treatment, and mortality among non-Hispanic White (NHW) patients and non-Hispanic Black (NHB) patients with NSCLC. Methods: This population-based retrospective cohort study included patients with NSCLC as a first primary malignancy diagnosed at age 20 and older between January 2007 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results (SEER) dataset released in April 2019. County-level racialized economic segregation was estimated using the Index of Concentration at the Extremes (ICE). We used multilevel logistic regression and multilevel Cox regression accounting for county-level clustering to estimate odds ratios (ORs) for late-stage diagnosis and non-adherence to guideline-recommended treatment, and hazard ratios (HRs) for overall mortality and lung cancer-specific mortality. Results: Of 203, 441 patients, 85.8% were NHW and 14.2% were NHB. Compared with patients living in the most privileged (lowest ICE quintile―segregated, high-income NHW) counties, patients living in the least privileged (highest ICE quintile―segregated, low-income NHB) counties had higher risks of late-stage diagnosis (OR=1.09, 95% CI: 1.02-1.16; Ptrend &amp;lt;.001), non-adherence to guideline-recommended treatment (OR=1.28, 95% CI: 1.16-1.41; Ptrend &amp;lt;.0001), lung cancer-specific mortality (HR=1.10, 95% CI: 1.07-1.14; Ptrend &amp;lt;.0001), and overall mortality (HR=1.12, 95% CI: 1.09-1.16; Ptrend &amp;lt;.0001). The association of segregation with treatment underutilization was stronger in NHW patients than NHB patients (Pinteraction =0.02). There was no significant difference in the segregation-related risk of late-stage diagnosis, lung cancer-specific mortality, or overall mortality between NHW and NHB patients. Conclusions: Living in segregated, low-income NHB counties was associated with increased risks of late-stage diagnosis, suboptimal treatment, and mortality among patients with NSCLC. Future research should investigate contributors to the adverse impact of residential segregation on lung cancer care and outcomes. Citation Format: Pratibha Shrestha, Min Lian, Ying Liu. Racialized economic segregation and disparities in late-stage diagnosis, treatment and mortality among patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4831.

Abstract 2153: The impact of socioeconomic and racial segregation on cancer stage at diagnosis, treatment and mortality among patients with small cell lung cancer

Abstract Background: Although studies have revealed the adverse impact of residential segregation on early detection, treatment, and survival of non-small cell lung cancer―a predominant type of lung cancers, it remains unknown regarding the role of residential segregation in treatment and outcomes of small cell lung cancer (SCLC)―a rare type of lung cancer characterized by rapid growth and poor prognosis. Therefore, we examined the associations of racialized socioeconomic segregation with risks of extensive-stage diagnosis, non-adherence to guideline-recommended treatment, and mortality among non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with SCLC. Methods: This population-based retrospective cohort study included patients who were diagnosed with SCLC as a first primary malignancy at age 20 and older between January 2007 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results. County-level racialized socioeconomic segregation was measured using the Index of Concentration at the Extremes (ICE). Multilevel logistic regression accounting for county-level clustering was used to estimate odds ratios (ORs) for extensive-stage diagnosis and non-adherence to guideline-recommended treatment. Hazard ratios (HRs) for lung cancer-specific mortality and all-cause mortality were computed using multilevel Cox regression. Results: Among 38,393 patients, 90.1% were NHW and 9.9% were NHB. Patients dwelling in the counties with the highest concentration of low-income NHB households (highest ICE quartile) had higher risks of non-adherence to guideline-recommended treatment (OR=1.23, 95% CI: 1.08-1.40; Ptrend &amp;lt;0.01), lung cancer-specific mortality (HR=1.08, 95% CI: 1.04-1.12; Ptrend &amp;lt;0.01), and all-cause mortality (HR=1.13, 95% CI: 1.09-1.17; Ptrend &amp;lt;0.0001) as compared with patients dwelling in the counties with the highest concentration of high-income NHW households (lowest ICE quartile). These associations were comparable between NHB and NHW patients. Racialized economic segregation was not significantly associated with extensive-stage diagnosis. Conclusions: Residing in the segregated, low-income NHB counties had adverse impacts on stage-appropriate treatment for SCLC and survival outcomes. Future research on the pathway(s) linking residential segregation to SCLC treatment underutilization and poor outcomes is warranted. Citation Format: Bayu B. Bekele, Min Lian, Ying Liu. The impact of socioeconomic and racial segregation on cancer stage at diagnosis, treatment and mortality among patients with small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2153.

Abstract 3424: Assessing a DNA methylation-based telomere length estimator in individuals with a heavy smoking history

Abstract Telomere length (TL) and DNA methylation are associated with age and smoking exposure, as well as aging-related outcomes including lung cancer and mortality. A DNA methylation-based TL score (DNAmTL) was developed to estimate TL using DNA methylation array data, both in blood. DNAmTL effectively estimates telomere-related aging using 140 CpGs that are moderately enriched in sub-telomeric regions and not included in existing epigenetic clocks. We examined DNAmTL in individuals with a heavy smoking history (mean 56 pack years, range 11-185) in a nested lung cancer case-control study of 350 cases and 350 controls from the β-Carotene and Retinol Efficacy Trial identified through 2005. Twenty-two controls became cases with additional follow-up through 2013, so 328 controls and 372 cases were considered for these analyses. Leukocyte TL was measured using quantitative polymerase chain reaction (T/S ratio, log2-transformed), and DNA methylation was assayed on the Illumina EPIC array, in blood samples obtained on average 4.9 years prior to diagnosis in cases. We observed weak positive Pearson correlations between DNAmTL and TL in cases (r=0.19, p=0.0003) and controls (r=0.14, p=0.009) that persisted after age-adjustment: r=0.16, p=0.002 and r=0.14, p=0.014, respectively. Age-adjusted DNAmTL, but not TL, was longer for female compared to male cases (T=3.6, p=0.0004) and controls (T=2.2, p=0.03), and for those in the placebo compared to the intervention arm in cases (T=2.1, p=0.03) and controls (T=2.3, p=0.02). Linear regression models of TL and DNAmTL adjusted for age, sex, and race and ethnicity were not statistically significant for smoking variables at blood draw (pack years, current vs former smoking status, cigarettes smoked per day during smoking history, years smoked, years since quit), nor asbestos exposure in either cases or controls. Longer age-adjusted DNAmTL was associated with a lower hazard ratio (HR) for time to lung cancer death (0.60, 95% Confidence Interval (CI): 0.37-0.97) among cases (n=313 lung cancer-specific mortality events) in Cox proportional hazards models adjusted for age, sex, race and ethnicity, and time from blood draw to diagnosis with stage as a stratification variable (early I/II, advanced III/IV, unknown). Analogous age-adjusted TL model showed a similar direction but did not reach statistical significance (HR 0.86, CI: 0.71-1.05). Further adjustment of these models by DNA methylation-estimated leukocyte proportions of granulocytes, monocytes, natural killer, CD8+T, and CD4+T (excluding B cells) yielded similar results for age-adjusted DNAmTL (HR 0.54, CI: 0.31-0.92) and age-adjusted TL (HR 0.87, CI: 0.71-1.05). Our results illustrate that while DNAmTL may not be closely associated with smoking exposure among heavily exposed individuals, shorter DNAmTL may be more strongly associated with lung cancer mortality than TL in individuals with a heavy smoking history. Citation Format: Laurie Grieshober, Stefan Graw, Matt J. Barnett, Gary E. Goodman, Chu Chen, Devin C. Koestler, Carmen J. Marsit, Jennifer A. Doherty. Assessing a DNA methylation-based telomere length estimator in individuals with a heavy smoking history [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3424.

Multilevel approaches to address disparities in lung cancer screening: a study protocol

BackgroundLow-dose computed tomography (lung cancer screening) can reduce lung cancer-specific mortality by 20–24%. Based on this evidence, the United States Preventive Services Task Force recommends annual lung cancer screening for asymptomatic high-risk individuals. Despite this recommendation, utilization is low (3–20%). Lung cancer screening may be particularly beneficial for African American patients because they are more likely to have advanced disease, lower survival, and lower screening rates compared to White individuals. Evidence points to multilevel approaches that simultaneously address multiple determinants to increase screening rates and decrease lung cancer burden in minoritized populations. This study will test the effects of provider- and patient-level strategies for promoting equitable lung cancer screening utilization.MethodsGuided by the Health Disparities Research Framework and the Practical, Robust Implementation and Sustainability Model, we will conduct a quasi-experimental study with four primary care clinics within a large health system (MedStar Health). Individuals eligible for lung cancer screening, defined as 50–80 years old, ≥ 20 pack-years, currently smoking, or quit < 15 years, no history of lung cancer, who have an appointment scheduled with their provider, and who are non-adherent to screening will be identified via the EHR, contacted, and enrolled (N = 184 for implementation clinics, N = 184 for comparison clinics; total N = 368). Provider participants will include those practicing at the partner clinics (N = 26). To increase provider-prompted discussions about lung screening, an electronic health record (EHR) clinician reminder will be sent to providers prior to scheduled visits with the screening-eligible participants. To increase patient-level knowledge and patient activation about screening, an inreach specialist will conduct a pre-visit phone-based educational session with participants. Patient participants will be assessed at baseline and 1-week post-visit to measure provider-patient discussion, screening intentions, and knowledge. Screening referrals and screening completion rates will be assessed via the EHR at 6 months. We will use mixed methods and multilevel assessments of patients and providers to evaluate the implementation outcomes (adoption, feasibility, acceptability, and fidelity).DiscussionThe study will inform future work designed to measure the independent and overlapping contributions of the multilevel implementation strategies to advance equity in lung screening rates.Trial registrationClinicalTrials.gov, NCT04675476. Registered December 19, 2020.

Comparing Lung Cancer Screening Strategies in a Nationally Representative US Population Using Transportability Methods for the National Lung Cancer Screening Trial

The National Lung Screening Trial (NLST) found that screening for lung cancer with low-dose computed tomography (CT) reduced lung cancer-specific and all-cause mortality compared with chest radiography. It is uncertain whether these results apply to a nationally representative target population. To extend inferences about the effects of lung cancer screening strategies from the NLST to a nationally representative target population of NLST-eligible US adults. This comparative effectiveness study included NLST data from US adults at 33 participating centers enrolled between August 2002 and April 2004 with follow-up through 2009 along with National Health Interview Survey (NHIS) cross-sectional household interview survey data from 2010. Eligible participants were adults aged 55 to 74 years, and were current or former smokers with at least 30 pack-years of smoking (former smokers were required to have quit within the last 15 years). Transportability analyses combined baseline covariate, treatment, and outcome data from the NLST with covariate data from the NHIS and reweighted the trial data to the target population. Data were analyzed from March 2020 to May 2023. Low-dose CT or chest radiography screening with a screening assessment at baseline, then yearly for 2 more years. For the outcomes of lung-cancer specific and all-cause death, mortality rates, rate differences, and ratios were calculated at a median (25th percentile and 75th percentile) follow-up of 5.5 (5.2-5.9) years for lung cancer-specific mortality and 6.5 (6.1-6.9) years for all-cause mortality. The transportability analysis included 51 274 NLST participants and 685 NHIS participants representing the target population (of approximately 5 700 000 individuals after survey-weighting). Compared with the target population, NLST participants were younger (median [25th percentile and 75th percentile] age, 60 [57 to 65] years vs 63 [58 to 67] years), had fewer comorbidities (eg, heart disease, 6551 of 51 274 [12.8%] vs 1 025 951 of 5 739 532 [17.9%]), and were more educated (bachelor's degree or higher, 16 349 of 51 274 [31.9%] vs 859 812 of 5 739 532 [15.0%]). In the target population, for lung cancer-specific mortality, the estimated relative rate reduction was 18% (95% CI, 1% to 33%) and the estimated absolute rate reduction with low-dose CT vs chest radiography was 71 deaths per 100 000 person-years (95% CI, 4 to 138 deaths per 100 000 person-years); for all-cause mortality the estimated relative rate reduction was 6% (95% CI, -2% to 12%). In the NLST, for lung cancer-specific mortality, the estimated relative rate reduction was 21% (95% CI, 9% to 32%) and the estimated absolute rate reduction was 67 deaths per 100 000 person-years (95% CI, 27 to 106 deaths per 100 000 person-years); for all-cause mortality, the estimated relative rate reduction was 7% (95% CI, 0% to 12%). Estimates of the comparative effectiveness of low-dose CT screening compared with chest radiography in a nationally representative target population were similar to those from unweighted NLST analyses, particularly on the relative scale. Increased uncertainty around effect estimates for the target population reflects large differences in the observed characteristics of trial participants and the target population.

A cost-effectiveness analysis of lung cancer screening with low-dose computed tomography and a polygenic risk score

IntroductionSeveral studies have proved that Polygenic Risk Score (PRS) is a potential candidate for realizing precision screening. The effectiveness of low-dose computed tomography (LDCT) screening for lung cancer has been proved to reduce lung cancer specific and overall mortality, but the cost-effectiveness of diverse screening strategies remained unclear.MethodsThe comparative cost-effectiveness analysis used a Markov state-transition model to assess the potential effect and costs of the screening strategies incorporating PRS or not. A hypothetical cohort of 300,000 heavy smokers entered the study at age 50–74 years and were followed up until death or age 79 years. The model was run with a cycle length of 1 year. All the transition probabilities were validated and the performance value of PRS was extracted from published literature. A societal perspective was adopted and cost parameters were derived from databases of local medical insurance bureau. Sensitivity analyses and scenario analyses were conducted.ResultsThe strategy incorporating PRS was estimated to obtain an ICER of CNY 156,691.93 to CNY 221,741.84 per QALY gained compared with non-screening with the initial start age range across 50–74 years. The strategy that screened using LDCT alone from 70–74 years annually could obtain an ICER of CNY 80,880.85 per QALY gained, which was the most cost-effective strategy. The introduction of PRS as an extra eligible criteria was associated with making strategies cost-saving but also lose the capability of gaining more LYs compared with LDCT screening alone.ConclusionThe PRS-based conjunctive screening strategy for lung cancer screening in China was not cost-effective using the willingness-to-pay threshold of 1 time Gross Domestic Product (GDP) per capita, and the optimal screening strategy for lung cancer still remains to be LDCT screening for now. Further optimization of the screening modality can be useful to consider adoption of PRS and prospective evaluation remains a research priority.

Program-Based Lung Cancer Care: A Prospective Observational Tumor Registry Linkage Study

IntroductionLow-dose computed tomography screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordant care. The impact of such program-based care on “real-world” lung cancer survival is unquantified. We evaluated outcomes of lung cancer care delivered through structured programs in a community health care system. MethodsWe conducted a cohort study linking institutional prospective observational LDCT, LNP and MDC databases with Tumor Registry of Baptist Cancer Center facilities. We categorized all patients diagnosed with lung cancer between 2011 and 2021 into program-based care versus non-program-based care cohorts. We compared patient characteristics, stage distribution, treatment modalities, survival and mortality in each pathway of care. ResultsOf 12,148 patients, 237, 1,165, 1,140 and 9,606 were diagnosed through the LDCT, LNP, MDC or no program, respectively; non-program-based care sequentially diminished from 96.3% to 66.5%, diagnosis through LDCT increased from 0.5% to 7.1%, LNP from 3.5% to 20.8%; and MDC alone decreased from a high of 12.8% in 2014 to 5.6% in 2021. Program-based care was associated with earlier stage (p < 0.001), higher surgical resection rates (p < 0.001), greater use of adjuvant therapy (p < 0.001), better aggregate and stage-stratified survival (p < 0.001), and lower all-cause and lung cancer-specific mortality (p < 0.001). Recipients of non-program-based care were considerably less likely to receive lung cancer treatment; results remained consistent when patients receiving no treatment were excluded. ConclusionsProgram-based care was associated with substantially better survival. Increasing access to program-based care should be explored as a matter of urgent public policy.

Opportunistic Screening With Low-Dose Computed Tomography and Lung Cancer Mortality in China

ImportanceDespite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality.ObjectiveTo evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China.Design, Setting, and ParticipantsThis cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023.ExposuresData collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening.Main Outcomes and MeasuresFollow-up outcome indicators included lung cancer–specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis.ResultsA total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64).Conclusions and RelevanceIn this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.

Assessment of interobserver concordance in radiomic tools for lung nodule classification, with a focus on BRODERS and SILA

While CT lung cancer screening reduces lung cancer-specific mortality, there are remaining challenges. Radiomic tools promiss to address these challenges, however, they are subject to interobserver variability if semi-automated segmentation techniques are used. Herein we report interobserver variability for two validated radiomic tools, BRODERS (Benign versus aggRessive nODule Evaluation using Radiomic Stratification) and CANARY (Computer-Aided Nodule Assessment and Risk Yield). We retrospectively analyzed the CT images of 95 malignant lung nodules of the adenocarcinoma spectrum using BRODERS and CANARY. Cases were identified at Mayo Clinic (n = 45) and Vanderbilt University Medical Center and Nashville/Veteran Administration Tennessee Valley Health Care System (n = 50). Three observers with different training levels (medical student, internal medicine resident and thoracic radiology fellow) each performed lung nodule segmentation. All methods were carried out in accordance with relevant guidelines and regulations. Interclass correlation coefficients (ICC) of 0.77, 0.98 and 0.97 for the average nodule volume, BRODERS cancer probability and Score Indicative of Lesion Aggression (SILA) which summarizes the distribution of the CANARY exemplars indicated good to excellent reliability, respectively. The dice similarity coefficient was 0.79 and 0.81 for the data sets from the two institutions. BRODERS and CANARY are robust radiomics tools with excellent interobserver variability. These tools are simple and reliable regardless the observer/operator’s level of training.

Abstract C113: Geographic variation in low-dose computed tomography scanning for lung cancer screening in the United States

Abstract Background: Early detection using low-dose computed tomography scanning reduces lung cancer specific mortality by 20%. Despite its efficacy and its recommendation by the United States Preventive Services Task Force, the uptake of lung cancer screening (LCS) among high-risk individuals (aged 55–80 years with a &amp;gt;30-pack-year smoking history and who currently smoke or have quit within the previous 15 years) remains low. The purpose of this study was to assess whether LCS uptake varies by geographic location. Methods: Data for this study were obtained from the 2019 Behavioral Risk Factor Surveillance System. After excluding ineligible subjects, 10,242 subjects were included in the final analysis. Multivariable logistic regression models were used to model the associations between the predictor and the outcome variable, adjusting for potential confounders. Results: In metropolitan statistical areas, individuals who reside outside the center city are less likely to receive LCS than those who reside in the center city (OR: 0.65; 95% CI: 0.43 – 0.98). Stratifying the data by race/ethnicity, we found a non-significant difference between Whites who reside in the center city and those outside the center city in LCS uptake (OR: 0.69; 95% CI: 0.45 – 1.06). Among Blacks (OR:0.10; 95% CI: 0.02 – 0.59) and other minorities (OR:0.10; 95% CI: 0.02 – 0.63), individuals who reside outside the center city are less likely to receive LCS than their respective counterparts residing in the center city. Nevertheless, we found a non-significant difference in LCS uptake between urban and rural counties (OR: 1.06; 95% CI: 0.76-1.48).Conclusions: LCS uptake is related to metropolitan statistical area (residents in the center city vs. outside the center city), but it is modified by race/ethnicity. This finding has important implications for policy makers and program planners in helping them design more effective interventions to promote LCS targeting racial/ethnic minorities residing outside the center city. Citation Format: Abdi T. Gudina, Lee A. Kehoe, Sara Hardy, Charles S. Kamen, Paula Cupertino. Geographic variation in low-dose computed tomography scanning for lung cancer screening in the United States [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C113.

Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation

PurposeWe assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation. Methods and MaterialsThis single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM). ResultsMedian age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0–22) and median heart mean dose was 8.7 Gy (IQR 4.6–14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM. ConclusionsWith modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC.

Wedge resection vs. segmentectomy for lung cancer measuring ≤ 2 cm with consolidation tumor ratio > 0.25.

We aimed to clarify the differences in prognosis between wedge resection and segmentectomy performed for cN0 non-small cell lung cancer (NSCLC) measuring ≤ 2 cm, with consolidation tumor ratio (CTR) > 0.25. This multicenter study included 570 patients with cN0 NSCLC (tumor size ≤ 2 cm, CTR > 0.25) who underwent wedge resection (n = 244) and segmentectomy (n = 326) between January 2010 and December 2018. After propensity score matching (PSM, 1:1 method), 182 patients were matched for clinical characteristics (age, sex, laterality, smoking index, tumor size, CTR, carcinoembryonic antigen value, positron-emission tomography-documented maximum standardized uptake value, clinical stage, and tumor disappearance rate) and intergroup comparison of disease-free survival (DFS) and overall survival (OS). Using Gray's test, an intergroup comparison of the cumulative incidence of lung cancer-specific mortality was performed. After PSM, similar DFS (5-year DFS, 79.9% vs. 87.1%, p = 0.103) and OS (5-year OS, 88.7% vs. 88.9%, p = 0.719) rates were observed in the wedge resection and segmentectomy groups. We observed no significant intergroup differences in lung cancer-specific mortality (5-year cumulative incidence: 4.6% vs. 3.5%; p = 0.235). Subgroup analysis revealed no specific subgroup demonstrating improved DFS or OS after undergoing wedge resection or segmentectomy. DFS, OS, and lung cancer-specific mortality were comparable between wedge resection and segmentectomy of cN0 NSCLC-tumor size ≤ 2 cm and CTR > 0.25. Large-scale prospective clinical trials are warranted to compare the prognoses of wedge resection and segmentectomy for these tumors.

Prognostic factors, treatment decisions, and nomograms for patients with second primary lung cancer following colorectal cancer: a population-based study.

Colorectal cancer (CRC) survival rates continue to improve, but the risk of developing a second primary malignancy (SPM) has also increased. The most common type of SPM observed after CRC is lung cancer. In this study, we explored the prognostic factors and clinical management decisions of patients with second primary lung cancer after colorectal cancer (SPLC-CRC). We identified the data of 1637 patients with SPLC-CRC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Cox regression modeling was used to construct a nomogram for predicting the prognosis of SPLC-CRC patients. The Fine-Gray competing risk model was used to determine the association between factors and cancer-specific mortality. After this, survival analyses were performed to assess the benefit of each treatment method on overall survival (OS). According to a multivariate analysis, age, gender, surgery, and chemotherapy were independent prognostic factors for the first primary malignancy (FPM), whereas age, primary site, TNM stage, tumor size, and treatment were independent prognostic factors for the second primary malignancy (SPM). For the training cohort column chart as well as the validation cohort column chart, using the concordance index of OS, 0.7611 and 0.7605 were calculated. A Fine-Gray competing risk model and survival analysis showed that there is a significant correlation between the treatment of FPM and the improvement in SPM survival rates, FPM-diagnosed patients who undergo surgery in different pathological stages exhibit higher overall survival rates, Patients in stages II, III, and IV benefit from combined surgery and chemotherapy. SPM surgery (P < 0.001, HR = 0.230, 95%CI 0.032-0.426) was a protective factor for lung cancer-specific mortality. Patients with local, regional, and even distant metastases may benefit more from SPM surgery (P < 0.001, P < 0.001, and P < 0.001, respectively). In patients who did not undergo SPM surgery, radiotherapy (P < 0.001) and chemotherapy (P = 0.008) improved OS. Treatment strategy for the first tumor affects the prognosis of the second tumor significantly. SPLC-CRC is treated primarily with surgery, regardless of whether the patient has metastases, as surgery may improve outcomes. In the event that a patient is unable to undergo surgery, chemotherapy or radiotherapy should be considered. Treatment decisions for SPLC-CRC patients may be influenced by these findings.

The association of race and curative-intent treatment with mortality outcomes among early-stage NSCLC.

e20563 Background: Racial disparities in early-stage non-small cell lung cancer (NSCLC) survival have persisted between blacks and whites in the past few decades. The role of receipt of curative-intent surgery and/or stereotactic body radiation therapy (SBRT) in this disparity is unclear. We examined the associations of race/ethnicity and curative-intent treatment (surgery and/or SRBT) with mortality outcomes among early-stage NSCLC patients, using population-based data from Florida, the third largest state in the US and the second state in the number of cancer cases diagnosed annually. Methods: Florida Cancer Data System (FCDS) data were used to estimate cancer-specific mortality for all patients diagnosed in the state between 2007 to 2018 for each racial/ethnic group: non-Hispanic black (NHB), Hispanic, and Asian/Pacific Islander (API)) and non-Hispanic whites (NHW). FCDS were further individually linked to population-based discharge data (94% match rate) containing patient-level comorbidities and treatment-specific information. Multivariable Cox proportional hazards regression models were applied to study the association of race/ethnicity and curative-intent treatment with lung cancer-specific mortality (LCSM). Competing risk analysis (deaths by other causes) for LCSM was performed. Results: We identified 63,872 early-stage NSCLC patients; 83.2% NHW, 6.6% NHB, 8.7% Hispanic, 0.77% API, and 0.79% other races; 72.2% of patients received curative-intent treatment (surgery and/or SRBT). The median lung cancer-specific survival time for all patients was 5.43 years (95% CI, 5.30-5.56). After inclusion of all clinical and sociodemographic factors including stage at diagnosis and comorbidities, race/ethnicity (NHB vs NHW: hazard ratio [HR], 1.06; 95% CI, 1.00-1.11) and curative-intent treatment (SBRT vs curative-intent surgery: HR, 1.87; 95% CI, 1.78-1.97;) were both independently associated with LCSM. Nevertheless, after combining the effect of race/ethnicity and curative-intent treatment in the same fully adjusted model, NHB patients who received curative-intent treatment experienced nearly identical survival as their NHW counterparts (HR, 0.95; 95% CI, 0.87-1.03). Similar findings were observed in competing risk analysis (subdistribution hazard ratio [sHR], 0.97; 95% CI: 0.89-1.02). Conclusions: In this racially diverse population, receipt of curative-intent treatment revealed comparable survival between NHB and NHW patients. The results underscore the importance of considering receipt of (specifically) curative-intent treatment rather than receipt of any form of surgery or radiotherapy in racial/ethnic survival disparities. The uptake of curative-intent surgery and SBRT, which currently stands at 56.5% and 9.4% respectively, should be increased to improve survival outcomes for early-stage NSCLC for all.

China lung cancer screening (CLUS) version 2.0 with new techniques implemented: Artificial intelligence, circulating molecular biomarkers and autofluorescence bronchoscopy

ObjectiveThe present study, CLUS version 2.0, was conducted to evaluate the performance of new techniques in improving the implementation of lung cancer screening and to validate the efficacy of LDCT in reducing lung cancer-specific mortality in a high-risk Chinese population. MethodsFrom July 2018 to February 2019, high-risk participants from six screening centers in Shanghai were enrolled in our study. Artificial intelligence, circulating molecular biomarkers and autofluorescencebronchoscopy were applied during screening. ResultsA total of 5087 eligible high-risk participants were enrolled in the study; 4490 individuals were invited, and 4395 participants (97.9%) finally underwent LDCT detection. Positive screening results were observed in 857 (19.5%) participants. Solid nodules represented 53.6% of all positive results, while multiple nodules were the most common location type (26.8%). Up to December 2020, 77 participants received lung resection or biopsy, including 70 lung cancers, 2 mediastinal tumors, 1 tracheobronchial tumor, 1 malignant pleural mesothelioma and 3 benign nodules. Lung cancer patients accounted for 1.6% of all the screened participants, and 91.4% were in the early stage (stage 0–1). ConclusionsLDCT screening can detect a high proportion of early-stage lung cancer patients in a Chinese high-risk population. The utilization of new techniques would be conducive to improving the implementation of LDCT screening.

Early Natural Menopause Is Associated With Poor Lung Health and Increased Mortality Among Female Smokers

ABSTRACT Menopause results from the decline of estrogen levels and is driven by ovarian aging. Some tissues, including the lung, may contribute to local estrogen synthesis in the postmenopausal state. Cigarette smoking is the most established factor for early menopause, and previous studies have shown that the menopause transition accelerated age-related decline of lung function following a restrictive disease pattern. In addition, studies have supported a potential synergistic effect of cigarette smoking and menopause on lung function. Delineating the effect of menopause timing and estrogen exposure on subsequent disease development may have important benefits for health maintenance and disease prevention in older women. This study aimed to assess the associations between early menopause and lung biomarkers, lung cancer risk, and cause-specific mortality. Data were obtained from the Pittsburg Lung Screening Study, a community-based research cohort of current and former smokers screened with low-dose computed tomography (CT) at baseline and 1 year later. Menstrual and reproductive history and data on respiratory symptoms were collected through questionnaires. Radiographic emphysema score was calculated from the baseline CT scan. Early menopause was defined as age at menopause of &lt;45 years. The study cohort included female Pittsburg Lung Screening Study participants who reported natural (n = 1038) or surgical (n = 628) menopause at study entry. A total of 1064 participants (63.9%) were current smokers with an average pack-years of 46.1 ± 19.8 at baseline. Early menopause was associated with several pathologies including self-reported wheezing (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.18–2.30; P &lt; 0.01), chronic bronchitis (OR, 1.73; 95% CI, 1.19–2.53; P &lt; 0.01), cardiovascular diseases (OR, 1.87; 95% CI, 1.13–3.11; P = 0.02), radiographic emphysema (OR, 1.70; 95% CI, 1.25–2.31; P &lt; 0.001), and incident airway obstruction (OR, 2.02; 95% CI, 1.03–3.96; P = 0.04) in women with natural menopause, but not surgical menopause except for physician-diagnosed cardiovascular diseases (OR, 4.03; 95% CI, 1.78–9.14; P &lt; 0.001). Trend tests for each of these outcomes in women with natural menopause identified monotonically increasing risk associated with younger age at menopause. Early menopause was associated with lower measurements of the lung function measurements forced expiratory volume in 1 second (FEV1; −104.8 ± 36.7 mL/s; P &lt; 0.01), forced vital capacity (FVC; −78.6 ± 38.2 mL; P = 0.04), and FEV1-to-FVC ratio (−2.1% ± 0.8%; P = 0.01) at baseline in women with natural menopause but not surgical menopause. The use of hormone therapy at any point was associated with higher baseline FEV1 levels and higher FEV1-to-FVC ratio at baseline among women with natural menopause. Early natural menopause was associated with a 40% increased risk of all-cause death with respiratory diseases (hazard ratio [HR], 2.32; 95% CI, 1.52–3.52; P &lt; 0.001), and early menopause was associated with twice the risk of lung cancer-specific mortality (HR, 1.94; 95% CI, 1.05–3.58; P = 0.03). This association was exacerbated by continuous cigarette smoking, with HRs of 4.65 (95% CI, 2.55–8.49; P &lt; 0.001) and 4.61 (95% CI, 2.63–8.07; P &lt; 0.001) for lung cancer and cancer mortality, respectively, among continuous smokers with early menopause compared with women with noncontinuous smoking and nonearly menopause. The results of this study demonstrate that among a postmenopausal cohort of middle-aged and older smokers, natural early menopause is associated with worse lung health and accelerated lung aging.