High Incidence Of Lung Cancer Research Articles

Incidence of the Frequency of Lung cancer in Kurdistan Province During 2005-2016

Background: Cancer is one of the principal causes of death in most countries of the world. Lung cancer is the deadliest and most expensive cancer in the world. In this study, the incidence of lung cancer in Kurdistan province was investigated for the first time in a specific period. Methods: In this cross-sectional study, 815 cases of lung cancer were investigated in Kurdistan province between 2005 and 2016. Reported cases of lung cancer were extracted at the Cancer Registry Center by gender, age, and morphology. Considering the population of 2005 as the standard population, the expected incidence rate was calculated, and the standardized incidence rate was estimated directly. Results: The results showed that the highest incidence of lung cancer was observed in 2016 and 2014 with 153 and 136 cases, respectively, and the lowest in 2009 and 2005, with 11 and 18 cases, respectively. The frequency of cases was observed in the age groups of 75-79 years in 2012 with 23 cases (22.77%) and in the age group of 70-74 years with 28 cases (18.30%) in 2016. The highest crude incidence was observed in 1394 with 12.47 and the lowest in 2013 with 1.10. Conclusion: According to the results of the present study, the incidence of lung cancer was higher in men than women and the incidence of the disease was higher in older ages. Analytical studies are necessary to find the causes of the disease and solve the problems related to this disease.

Predicting the risk of lung cancer using machine learning: A large study based on UK Biobank.

In response to the high incidence and poor prognosis of lung cancer, this study tends to develop a generalizable lung-cancer prediction model by using machine learning to define high-risk groups and realize the early identification and prevention of lung cancer. We included 467,888 participants from UK Biobank, using lung cancer incidence as an outcome variable, including 49 previously known high-risk factors and less studied or unstudied predictors. We developed multivariate prediction models using multiple machine learning models, namely logistic regression, naïve Bayes, random forest, and extreme gradient boosting models. The performance of the models was evaluated by calculating the areas under their receiver operating characteristic curves, Brier loss, log loss, precision, recall, and F1 scores. The Shapley additive explanations interpreter was used to visualize the models. Three were ultimately 4299 cases of lung cancer that were diagnosed in our sample. The model containing all the predictors had good predictive power, and the extreme gradient boosting model had the best performance with an area under curve of 0.998. New important predictive factors for lung cancer were also identified, namely hip circumference, waist circumference, number of cigarettes previously smoked daily, neuroticism score, age, and forced expiratory volume in 1 second. The predictive model established by incorporating novel predictive factors can be of value in the early identification of lung cancer. It may be helpful in stratifying individuals and selecting those at higher risk for inclusion in screening programs.

Abstract 6275: Exposure to neighborhood violence rewires glucocorticoid receptor binding and drives proliferation and invasiveness in lung tumor samples

Abstract Background: Despite smoking less, Black men experience higher incidence of lung cancer compared to white men. This health disparity is even more prevalent in Black men from Chicago, suggesting local neighborhood factors impacting tumorigenesis. Preliminary data indicate that, compared to white men, Black men are more likely to reside in neighborhoods with high levels of violence and have elevated levels of hair cortisol. Objective: To understand the link between lung tumorigenesis and exposure to neighborhood violence, our objective is to investigate the chromatin recruitment of the receptor for cortisol, called the glucocorticoid receptor (GR), and to correlate this recruitment with target gene expression levels. Methods: Utilizing CUT & RUN, we identified the gene binding sites of GR using 15 lung tumor and corresponding healthy tissue samples from lung cancer patients living in Chicago. GR recruitment to chromatin was correlated with the neighborhood homicide rate obtained using patients’ zip codes. Spatial transcriptome profiles for these 15 lung tumor samples were obtained from the Space Ranger pipeline and gene expression hot spots of GR target genes were visualized using Loupe Browser (10x Genomics). Results: GR recruitment to regulatory regions of chromatin increases with greater zip code level violence rates. In patients from high violence neighborhoods, tumor samples had higher magnitude of binding compared to normal neighboring tissue. In tumor samples from patients living in high violence compared to low violence neighborhoods, GR binding is seen in genes that are associated with increased tumor aggressiveness. Hot-spot analysis of these genes found strong co-expression of genes associated with proliferation and invasion in samples from high violence but not low violence neighborhoods. Conclusion: Exposure to neighborhood violence may impact tumor biology via increased GR recruitment to genes associated with proliferation and invasion. Citation Format: Hannah Heath, Jin Young Yoo, Vani Sharma, Hannah McGee, Aiman Soliman, Abeer Mohamed, Alicia K. Matthews, Robert Winn, Zeynep Madak-Erdogan, Sage Kim. Exposure to neighborhood violence rewires glucocorticoid receptor binding and drives proliferation and invasiveness in lung tumor samples [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 6275.

Abstract 1004: Establishing lung adenocarcinoma cell lines to mitigate lung cancer health disparities

Abstract Lung cancer remains the leading cause of cancer death worldwide and is a pronounced source of cancer health disparities. Black/African American (B/AA) individuals demonstrate the highest lung cancer death rates when compared to other ethnic/racial groups. B/AA males exhibit a 15% higher lung cancer death rate and a 12% higher lung cancer incidence when compared to White males. Lung adenocarcinoma (LUAD) is the most common histological subtype in all races including B/AA. To study lung cancer and its related disparities, essential tools such as lung cancer cell lines are important; they can be used for molecular studies of lung cancer development, progression, development of new therapies and pre-clinical drug testing. We reviewed the literature (Leon et al. 2023, Frontiers in Oncology, Vol. 13, p. 1187585, 2023) and identified only 30 unique B/AA cell lines out of ~800 cell lines available, with the majority of cell lines being from White and Asian patients. Moreover, only 6 B/AA cell lines were derived from patients with LUAD. We are in the process of developing additional LUAD cell lines from patients as well as alveolar epithelial cell lines that can be used to model LUAD development. In addition, we are generating multiple independent isogenic cell line variants from existing lung cancer cell line NCI-H23, derived from a B/AA male patient harboring a KRASG12C heterozygous mutation. We are using CRISPR/Cas-9-based genome editing to replace the KRASG12C mutation with other KRAS mutations found in B/AA patients, including KRASG12V, KRASG12D, KRASG12A, and KRASG13C. We will perform whole genome sequencing to exclude off target effects of the CRISPR engineering. We will use isogenic cell lines to test the efficacy of polyisoprenylated cysteinyl amide inhibitors (PCAIs) and other drugs on cell lines bearing the different KRAS mutations. PCAIs were developed to target cells carrying mutant KRAS. Our efforts will provide tools to limit cancer health disparities and serve as a foundation for future research. Supported by grants U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH)/National Cancer Institute (NCI) and the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI. Citation Format: Sofia Lugo, Christopher Leon, Matthew Gladstone, Chunli Yan, Nazarius S. Lamango, Ite A. Offringa, Kweku Ofosu-Asante, Yong Huang, Justin K. Mensah-Mamfo. Establishing lung adenocarcinoma cell lines to mitigate lung cancer health disparities [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 1004.

Abstract 4830: Predicting drug treatment response in African American lung cancer patients who smoke

Abstract Background: Lung cancer is the third most commonly diagnosed cancer in the US and the leading cause of cancer-related death. African Americans (AAs) have higher lung cancer incidence and mortality rates, and lower survival rates, when compared to their European American (EA) counterparts. It is widely known that cigarette smoking is the strongest risk factor for lung cancer development, but it also plays a significant role in clinical outcome. Cigarette smoking after lung cancer diagnosis (up to 30% patients) comes with several risks, including increased secondary tumors and mortality rates (by 20%), as well as poor treatment outcomes (higher radiation and chemotherapy failure and higher drug clearance). There are limited transcriptomic studies that describe molecular characterizations of AA smokers with lung cancer to predict treatment outcomes. Hypothesis: Cigarette smoking leads to greater drug resistance-related gene expression in AA lung cancer patients. Methods: mRNA expression changes in an AA (NCI-H2172) and EA (NCI-H1944) lung cancer cell line pair exposed to liquid cigarette smoke condensate (CSC) were profiled. The cell lines were matched based on age (62 years), sex (female), histology (lung adenocarcinoma, LUAD, the most common subtype), and culture properties (adherent). The CSC was derived from Murty Pharmaceuticals and prepared by smoking University of Kentucky's 3R4F Standard Research Cigarette on an FTC Smoke Machine. A total of 500,000 cells per well were treated for one hour under standard incubation conditions (37°C, pH 7.0, 5% CO2). Cells were pelleted, RNAs were isolated, treated with DNAse-I to remove contaminating genomic DNA, quantified, and sent for bulk mRNA-sequencing (Novogene Co). Three biological replicates and technical triplicates were performed. Partek Flow and Partek Genomics Suite workflows were used to identify population-specific differentially expressed gene (DEG) signatures and pathway enrichment after CSC exposure. DEG were profiled in LUAD tissues from current smokers in an AA and EA TCGA cohort (n = 18 AAs, 86 EAs). Results: Population-specific gene expression changes were discovered (n = 52 AA DEGs, n = 31 EA DEGs; P <0.001). All of the DEGs were mutually exclusive with no overlap. Some pathways were shared between both populations and others were unique. PI3K/Akt/mTOR signaling pathway enrichment was unique in AA LUAD cells and ECM receptor interactions were distinct in EA LUAD cells. AKT2 (which activates mTOR) had significantly higher expression in LUAD tumor tissues from current AA smokers compared to current EA smokers. Conclusion: Population-specific PI3K/Akt/mTOR pathway alterations may help explain drug resistance in LUAD tumors from AA patients. PI3K signaling is considered a significant cause of resistance to chemotherapy, targeted therapy, and immunotherapy. Future Directions: Expose AA and EA LUAD cell lines to CSC and PI3K/Akt/mTOR pathway inhibitors. Citation Format: Mia Ray, Isaiah Osei-Gyening, Kwabena Acheampong, Marisa Riebesell, Khadijah A. Mitchell. Predicting drug treatment response in African American lung cancer patients who smoke [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 4830.

Analysis of Lung Cancer Disparities in Northwest Indiana

Background and Hypothesis: Lung cancer is the first leading cause of cancer death worldwide (~1.8 million deaths pa.). Low-Dose Computed Tomography (LDCT) screening is a preventative measure to diagnose lung cancer at an early stage, which increases the chance of survival. Northwest Indiana is a diverse region (830,000 pop.) that faces unique challenges to equitable health outcomes and access to preventative treatments, particularly within minoritized communities from a low socioeconomic status. We investigated whether the vulnerable populations of Northwest Indiana have a higher incidence of lung cancer, low LDCT screening rates, and a late stage of diagnosis, in order to identify potential gaps in healthcare access and delivery.
 Methods: We used LDCT screening (n = 2,481), lung cancer incidence (n = 268) and staging (n = 257) data from ZIP Codes of six cities/towns in Northwest Indiana, provided by an urban hospital system in Northwest Indiana between 2018 and 2023. The cities/towns were grouped into ‘lower’ and ‘upper’ income according to median household income level reported by 2020 U.S. census data. Chi-Squared tests were used to determine significance.
 Results: There is no significant difference in the incidence of lung cancer between upper and lower income cities/towns (p= 0.163). However, there is a significant difference in stage I, II, and IV diagnoses between the two income groups (p = 0.021, 0.007, and 0.013 respectively), which demonstrates an inverse relationship between income level and stage of diagnosis. The lower income group is diagnosed at a younger age (p = 0.02) with advanced stage lung cancer, despite similar rates of lung cancer incidence.
 Conclusion and Potential Impact: Barriers to screening for vulnerable populations in urban areas include patient-provider mistrust, health illiteracy, and lack of healthcare services. Late stage diagnosis necessitates the development of local interventions to increase early screening.

Increased Utilization of Low-Dose CT for Lung Cancer Screening at an Arkansas Community Oncology Clinic

BackgroundLow-dose CT (LDCT) is underused in Arkansas for lung cancer screening, a rural state with a high incidence of lung cancer. The objective was to determine whether offering free LDCT increased the number of high-risk individuals screened in a rural catchment area. MethodsThere were 5,402 patients enrolled in screening at Highlands Oncology, a community oncology clinic in Northwest Arkansas, from 2013 to 2020. Screenings were separated into time periods: period 1 (10 months for-fee), period 2 (10 months free with targeted advertisements and primary care outreach), and period 3 (62 months free with only primary care outreach). In all, 5,035 high-risk participants were eligible for analysis based on National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Enrollment rates, incidence densities (IDs), Cox proportional hazard models, and Kaplan-Meier curves were performed to investigate differences between enrollment periods and high-risk groups. ResultsPatient volume increased drastically once screenings were offered free of charge (period 1 = 4.6 versus period 2 = 66.0 and period 3 = 69.8 average patients per month). Incidence density per 1,000 person-years increased through each period (IDPeriod 1 = 17.2; IDPeriod 2 = 20.8; IDPeriod 3 = 25.5 cases). Cox models revealed significant differences in lung cancer risk between high-risk groups (P = .012) but not enrollment periods (P = .19). Kaplan-Meier lung cancer-free probabilities differed significantly between high-risk groups (log-rank P = .00068) but not enrollment periods (log-rank P = .18). ConclusionsThis study suggests that eligible patients are more receptive to free LDCT screening, despite most insurances not having a required copay for eligible patients.

THU501 Examining The Link Between Exposure To Neighborhood Violence And PRMT6 And Glucocorticoid Receptor Binding To Chromatin In Lung Tumors

Abstract Disclosure: H. Heath: None. S. Kim: None. Z. Madak Erdogan: None. Despite smoking less, Black men experience a higher incidence of lung cancer than white men. This health disparity is even more prevalent in Black men from Chicago, suggesting local neighborhood factors impacting tumorigenesis. Preliminary data found that Black men compared to white men exhibit overexpression of the epigenetic regulator known as PRMT6, have elevated levels of hair cortisol, and live in neighborhoods with disproportionately high levels of violence. This research aims to investigate the receptor for cortisol called glucocorticoid receptor (GR), and PRMT6 recruitment to chromatin and to correlate this recruitment with tumor cortisol levels and exposure to neighborhood violence. Using a version of ChIP-sequencing known as CUT & RUN, the gene binding sites of PRMT6 and GR will be identified using 16 lung tumor samples from patients living in Chicago. Cortisol levels present in lung tumors will be detected using LC-MS. These cortisol levels will be correlated with GR and PRMT6 recruitment to chromatin and neighborhood homicide data obtained using patients’ zip codes. We hypothesize that PRMT6 and GR will be recruited to regulatory regions of genes related to increased lung tumor aggressiveness. We also anticipate that cortisol levels will correlate with neighborhood violence levels and elevated PRMT6 and GR colocalization, indicating chronic exposure to stress as a regulator of lung tumor formation. Presentation: Thursday, June 15, 2023

Understanding Barriers and Facilitators to High-Quality Cancer Care Among Veterans With Lung Cancer: A Qualitative Study.

Veteran populations have higher lung cancer incidence and worse overall survival compared with non-Veteran populations. Although recent clinical advancements have reduced lung cancer death rates, these advances are not routinely received among Veteran populations because of multilevel factors, including Veterans' complex comorbidities, limited health literacy, and other economic and social disadvantages. This study aimed to assess Veterans' perspectives regarding their lung cancer care with a specific focus on identifying modifiable barriers to evidence-based care delivery. We conducted 1:1 semistructured interviews with 24 Veterans diagnosed with lung cancer at the Veterans Affairs Palo Alto Health Care System. All interviews were recorded, transcribed, and analyzed using the constant comparative method of qualitative analysis. Four themes emerged. These included (1) social and economic disadvantages can prevent routine delivery of evidence-based cancer care; (2) fragmented care contributes to worsening patient mental and emotional well-being; (3) lack of health system interventions to address limited health literacy inhibits patient engagement in shared decision making regarding diagnosis, genomic and molecular testing, targeted and other treatments, and end-of-life care; and (4) deep appreciation for care and VA trustworthiness facilitates adherence to cancer care recommendations. This study revealed critical gaps in lung cancer care delivery and the role of institution-engendered trust in overcoming barriers in the VA system. Targeted solutions should address the identified barriers to routine, evidence-based lung cancer care delivery among Veterans.

Ethnic differences of genetic risk and smoking in lung cancer: two prospective cohort studies.

The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 1.15, P = 0.028]. A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 (95% CI, 7.01-17.94)], but not in the CKB. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk. Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer.

The Unmet Diagnostic and Treatment Needs in Large Cell Neuroendocrine Carcinoma of the Lung.

Large cell neuroendocrine carcinoma of the lung (LCNEC) is currently classified as a rare lung cancer subtype, but given the high incidence of lung cancer, the overall number of cases is considerable. The pathologic diagnosis of LCNEC is mainly based on the microscopic appearance of the tumor cells, the mitotic rate, the amount of intra-tumoral necrosis, and the presence of positive neuroendocrine markers identified by immunohistochemistry. Recently, a subdivision into two main categories was proposed based on mutation signatures involving the RB1, TP53, KRAS, and STK11/LKB1 genes, into SCLC-like (small cell lung cancer-like) and NSCLC-like (non-small cell lung cancer-like) LCNEC. In terms of treatment, surgery is still the best option for resectable, stage I-IIIA cases. Chemotherapy and radiotherapy have conflicting evidence. Etoposide/platinum remains the standard chemotherapy regimen. However, based on the newly proposed LCNEC subtypes, some retrospective series report better outcomes using a pathology-driven chemotherapy approach. Encouraging outcomes have also been reported for immunotherapy and targeted therapy, but the real impact of these strategies is still being determined in the absence of adequate prospective clinical trials. The current paper scrutinized the epidemiology, reviewed the reliability of pathologic diagnosis, discussed the need for molecular subtyping, and reviewed the heterogeneity of treatment algorithms in LCNEC.

Disparities in lung cancer

Lung cancer is the second most common cancer and the leading cause of cancer death among men and women in the United States. Despite a substantial decline in lung cancer incidence and mortality across all races in the last few decades, medically underserved racial and ethnic minority populations continue to carry the greatest burden of disease throughout the lung cancer continuum. Black individuals experience a higher incidence of lung cancer due to lower rates of low-dose computed tomography screening, which translate into advanced disease stage at diagnosis and poorer survival outcomes compared with White individuals. With respect to treatment, Black patients are less likely to receive gold standard surgery, have access to biomarker testing or high-quality treatment compared with White patients. The reasons for those disparities are multifactorial and include socioeconomic (eg, poverty, lack of health insurance, and inadequate education), and geographic inequalities. The objective of this article is to review the sources of racial and ethnic disparities in lung cancer, and to propose recommendations to help address them.

Incidence profile of four major cancers among migrants in Australia, 2005–2014

PurposeTo compare the incidence profile of four major cancers in Australia by place of birth.MethodsIn this retrospective population-based cohort study, the analysis included 548,851 residents diagnosed with primary colorectum, lung, female breast, or prostate cancer during 2005–2014. Incidence rate ratio (IRR) and 95% confidence intervals (CI) were calculated for migrant groups relative to Australian-born.ResultsCompared with Australian-born residents, most migrant groups had significantly lower incidence rates for cancers of the colorectum, breast and prostate. The lowest rates of colorectal cancer were among males born in Central America (IRR = 0.46, 95% CI 0.29–0.74) and females born in Central Asia (IRR = 0.38, 95% CI 0.23–0.64). Males born in North-East Asia had the lowest rates of prostate cancer (IRR = 0.40, 95% CI 0.38–0.43) and females born in Central Asia had the lowest rates of breast cancer (IRR = 0.55, 95% CI 0.43–0.70). For lung cancer, several migrant groups had higher rates than Australian-born residents, with the highest rates among those from Melanesia (males IRR = 1.39, 95% CI 1.10–1.76; females IRR = 1.40, 95% CI 1.10–1.78).ConclusionsThis study describes cancer patterns among Australian migrants, which are potentially helpful in understanding the etiology of these cancers and guiding the implementation of culturally sensitive and safe prevention measures. The lower incidence rates observed for most migrant groups may be maintained with continued emphasis on supporting communities to minimize modifiable risk factors such as smoking and alcohol consumption and participation in organized cancer screening programmes. Additionally, culturally sensitive tobacco control measures should be targeted to migrant communities with high lung cancer incidence rates.

Abstract 5218: Genome-wide association study of African Americans reveals new susceptibility loci contributing to lung cancer and mechanisms of population-specific etiology

Abstract Lung cancer incidence and mortality in the U.S. have substantial ethnic disparities. African Americans of both sexes have the high incidence rate at 56.8 and the highest death rate at 38.1 per 100,000 people from 2015 to 2019. Non-Hispanic black men have the highest incidence at 73.9 and the highest death rate at 56.3 per 100,000 people. While many genome-wide association studies (GWAS) of lung cancer have discovered ~45 putative risk loci, a large proportion of the heritability of lung cancer remains unexplained. To date, most single population-based GWAS have been performed in Europeans while there are a few Asian ancestry-specific genetic studies and two cross-ancestry studies. Non-European GWAS of lung cancer has been underrepresented. Although African Americans have higher lung cancer incidence and poorer lung cancer survival rate, and smoke fewer cigarettes per day compared to Europeans, few comprehensive GWAS of lung cancer in African Americans has been conducted. This study aims to decipher the genetic component of predisposition to lung cancer among African Americans. This study aims to decipher the genetic component of predisposition to lung cancer among African Americans. We conducted an African-ancestry GWAS comprising 2,280 lung cancer cases and 4,301 controls to comprehensively characterize common and low-frequency lung cancer genetic susceptibility loci using HRC imputed lung cancer data. The novel variants in or near VWF on 12p13.31 (OR=1.29, P=6.93 × 10−9) for overall lung cancer and GACAT3 on 2p24.3 (0.65, 1.24 × 10−9), TRIP13 on 5p15.33 (3.49, 1.00 × 10−8), ERC1 on 12p13.33 (4.64, 6.08 × 10−9), LMAN1L (near CYP1A1) on 15q24.1 (4.25, 8.71 × 10−9) for lung squamous cell cancer were identified at a genome-wide significance level. Our GWAS of lung cancer identified five novel genetic susceptibility associations and confirmed several variants on 15q25 and 19q13. Further works are required to elucidate the possible biological mechanisms underlying these associations among lung cancer and histological subtypes in African Americans. Citation Format: Jinyoung Byun, Younghun Han, Xiangjun Xiao, Christine Lusk, Hoda J. Badr, Rayjean Hung, Ann G. Schwartz, Christopher I. Amos, INTEGRAL Consortium. Genome-wide association study of African Americans reveals new susceptibility loci contributing to lung cancer and mechanisms of population-specific etiology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5218.

Unique profile on the progress free survival and overall survival in patients with advanced non-small cell lung cancer in the Qujing area, Southwest China.

China's southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing. Tissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy. In cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations. These findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.

Disparities in cancer incidence by rurality in California.

Cancer rates in rural areas across the United States have different patterns than in urban areas. This study examines associations between rurality and incidence for the top 5 cancers in California and evaluates whether these associations vary jointly by sex, race, and ethnicity. We used 2015-2019 California Cancer Registry data to compare incidence rate ratios (IRRs) and trends for breast, prostate, lung, colorectal, and skin (melanoma) cancers. We leveraged census tract aggregation zones and 7 levels of percentage rural population (0%, >0% to <10%, 10% to <20%, 20% to <30%, 30% to <40%, 40% to <50%, and 50+%). Zones with higher proportions of rural population were significantly associated with lower incidence of female breast cancer and prostate cancer, though the trends were not statistically significant overall. Zones with higher proportions of rural population were significantly associated with higher incidence of lung cancer and melanoma. There were no statistically significant trends for colorectal cancer overall. Comparing areas with 50% and over rural population with areas with 0% rural population, the IRR for lung cancer in Hispanic females was higher (IRR = 1.43, 95% confidence interval [CI] = 1.17 to 1.74) than in Hispanic males (IRR = 0.90, 95% CI = 0.72 to 1.11). Also, in areas with 50% or more rural population, the IRR for melanoma was higher in Hispanic females (IRR = 1.75, 95% CI = 1.23 to 2.45) than non-Hispanic White females (IRR = 0.87, 95% CI = 0.80 to 0.95). Our findings show that rurality is associated with cancer incidence and underscore the importance of jointly examining rural disparities with sex, race, and ethnicity by cancer site.

Abstract A122: Development and pilot testing of an EHR-based provider-level intervention to promote equity in lung cancer screening

Abstract Introduction: Black/African Americans (AA) have the highest lung cancer incidence and mortality compared to other racial and ethnic groups; however, provider-initiated discussions with eligible patients about lung cancer screening (LCS) are low overall, and AA and other minority individuals are less likely than Whites to have these discussions. To target lack of provider-initiated discussion about lung screening, we describe the development and feasibility of a provider-level prompt for a planned multilevel intervention to promote equitable uptake of LCS. Methods: We used an iterative process to refine a provider prompt delivered in the Electronic Health Record (EHR; Cerner Health). First, we conducted surveys with MedStar Health primary care providers (N=22) to examine existing system tools for identifying screen-eligible patients, design-related provider preferences (e.g., content, format), and delivery and usefulness of the prompt (e.g., timing, likelihood of prompting LCS discussion). Next, we completed shadowing (N=11 visits) to observe the primary care clinic workflow. We conducted usability testing (N=7) to finalize the prompt. We partnered with a MedStar Primary Care Clinic (Mitchellville, MD) to evaluate the feasibility of implementing the prompt over a 6 month period. Utilizing an automated report to identify patients (50-80 years with a smoking history) with an upcoming visit, we sent the prompt to providers prior to the visits to notify them of the patient’s possible eligibility and encourage discussion of the test. Results: Of the providers who completed the survey, the majority were attending physicians (81.8%). Providers were shown a mock-up and 95% reported it was enough information to prompt them to have a discussion with their patients. Most (86.4%) said the optimal time to receive the prompt would be within 24 hours of the visit. During the usability testing, providers were given two formats and patient scenarios and they identified content that should be removed (e.g., screenshots of how to place the order, repeated hyperlinks). Most preferred the patient smoking history presented in a tabular format and liked the addition of color for visual appeal. In the 12-month period pre-intervention, the pilot clinic patient population (N=1223) were majority AA (91%) and over 90% were missing complete pack-year data (required for LCS eligibility). During the pilot period, 64% of records were eligible for the provider prompt and 45% of patients' pack-year data were updated post-appointment. Conclusions: These findings describe a promising provider-level intervention to identify patients and prompt provider-initiated discussion about smoking history and LCS. As a next step, we will evaluate the impact of the prompt on LCS orders. We will also pilot a patient-level intervention to improve provider-patient communication about screening. We intend to look at the effect of these combined interventions on LCS behaviors among AA and White patients. Citation Format: Randi M. Williams, Julia Whealan, Joseph Blumenthal, Kristie Foley, Kathryn L. Taylor, Lucile Adams-Campbell, Kristen E. Miller, Rachelle Barnes, William F. DuBoyce, Heather Kratz, Kenneth W. Lin. Development and pilot testing of an EHR-based provider-level intervention to promote equity in lung cancer screening [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A122.

A Cross-Sectional Study on the Acceptability of Implementing a Lung Cancer Screening Program in Belgium

Lung cancer is the most common and deadliest cancer in the world, and its incidence is expected to grow. Nonetheless, this growth can be contained through smoking cessation programs and effective lung cancer screening programs. In 2018, Belgium had the seventh highest incidence of lung cancer in the world, with lung cancer incidence accounting for 11.8% of all cancers diagnosed and 23.8% of all cancer-related deaths that same year. The aims of this study were to determine the overall acceptability of a lung cancer screening program in the Flemish population and to determine the main factors that would influence the overall acceptability of such a program. A questionnaire-based cross-sectional study was performed in the Flemish population and distributed online and on paper. The results are presented with the variables of interest and the main outcome, i.e., the acceptability of participating in such a program if implemented. Odds ratios were used to compare acceptability between subgroups. A multivariate regression model was used to determine the key factors that would have the largest impact on the level of acceptability and, thus, on the possible efficiency of such a program. This study estimated that acceptability of participating in a lung cancer screening program was 92%. Irrespective of the smoking status, levels of acceptability were higher than 89%. The key factors which could significantly influence the acceptability of a lung cancer screening program were individuals with low education, low protective factor knowledge and total knowledge, and lung cancer screening reimbursement, which were significantly associated with acceptability (0.01, 0.001, 0.01, and 0.05 respectively). Low protective factor knowledge decreased the log odds of acceptability 3.08-fold. In conclusion, the acceptability of implementing a lung cancer screening program in Flanders seems to be extremely high and would be well received by all. When implementing such a program, policymakers should aim for it to be reimbursed, campaigns should be gender-specific, focused on those with lower educational and socioeconomic status, and there should be investment in increasing total knowledge about lung cancer and knowledge about protective factors.

Validation of a Deep Learning–Based Model to Predict Lung Cancer Risk Using Chest Radiographs and Electronic Medical Record Data

Lung cancer screening with chest computed tomography (CT) prevents lung cancer death; however, fewer than 5% of eligible Americans are screened. CXR-LC, an open-source deep learning tool that estimates lung cancer risk from existing chest radiograph images and commonly available electronic medical record (EMR) data, may enable automated identification of high-risk patients as a step toward improving lung cancer screening participation. To validate CXR-LC using EMR data to identify individuals at high-risk for lung cancer to complement 2022 US Centers for Medicare & Medicaid Services (CMS) lung cancer screening eligibility guidelines. This prognostic study compared CXR-LC estimates with CMS screening guidelines using patient data from a large US hospital system. Included participants were persons who currently or formerly smoked cigarettes with an outpatient posterior-anterior chest radiograph between January 1, 2013, and December 31, 2014, with no history of lung cancer or screening CT. Data analysis was performed between May 2021 and June 2022. CXR-LC lung cancer screening eligibility (previously defined as having a 3.297% or greater 12-year risk) based on inputs (chest radiograph image, age, sex, and whether currently smoking) extracted from the EMR. 6-year incident lung cancer. A total of 14 737 persons were included in the study population (mean [SD] age, 62.6 [6.8] years; 7154 [48.5%] male; 204 [1.4%] Asian, 1051 [7.3%] Black, 432 [2.9%] Hispanic, 12 330 [85.2%] White) with a 2.4% rate of incident lung cancer over 6 years (361 patients with cancer). CMS eligibility could be determined in 6277 patients (42.6%) using smoking pack-year and quit-date from the EMR. Patients eligible by both CXR-LC and 2022 CMS criteria had a high rate of lung cancer (83 of 974 patients [8.5%]), higher than those eligible by 2022 CMS criteria alone (5 of 177 patients [2.8%]; P < .001). Patients eligible by CXR-LC but not 2022 CMS criteria also had a high 6-year incidence of lung cancer (121 of 3703 [3.3%]). In the 8460 cases (57.4%) where CMS eligibility was unknown, CXR-LC eligible patients had a 5-fold higher rate of lung cancer than ineligible (127 of 5177 [2.5%] vs 18 of 2283 [0.5%]; P < .001). Similar results were found in subgroups, including female patients and Black persons. Using routine chest radiographs and other data automatically extracted from the EMR, CXR-LC identified high-risk individuals who may benefit from lung cancer screening CT.

Concentration, Source, and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons: A Pilot Study in the Xuanwei Lung Cancer Epidemic Area, Yunnan Province, China

Polycyclic aromatic hydrocarbons (PAHs) are toxic and hazardous volatile environmental pollutants that have been studied as possible major causative agents of lung cancer in Xuanwei. In this paper, indoor and outdoor PM2.5 samples were collected from two homes at different time periods in Hutou, the lung cancer epidemic area in Xuanwei. The results showed that PAH pollution levels from coal combustion in Xuanwei lung cancer epidemic area were significant. The mass concentrations of total PAHs, major carcinogenic compounds, and benzo[a]pyrene-based equivalent concentration (BaPeq) were significantly higher in the coal-using home than in the electricity-using home. For the coal-using home, the PAHs were mainly derived from coal combustion. For the electricity-using home, the PAHs might have been a combination of traffic and coal combustion sources. The human health risk due to inhalation exposure to the PAHs was represented by the incremental lifetime cancer risk (ILCR) of the inhalation exposure. The results showed that the indoor cancer risk for the coal-using home in Xuanwei is higher than that of the electricity-using home and much higher than that of Chinese megacities such as Beijing and Tianjin. Long-term exposure to indoor coal-burning environments containing high levels of PAHs may be one of the main reasons for the high incidence of lung cancer in Xuanwei.