Background: Lung cancer screening (LCS) with low-dose CT (LDCT) remains markedly underutilized. Prior studies suggest that perceptions regarding LCS may influence intention to undergo LDCT; however, little is known about these beliefs and behaviors in vulnerable populations. We examined LCS-related health beliefs and LDCT completion in an urban safety-net health care system. Patients and Methods: We surveyed English- and Spanish-speaking individuals between February 2017 and February 2019 who had been scheduled for, but had not yet undergone, an initial LDCT. Survey items were adapted from validated measures, including the Lung Cancer Screening Health Belief Scales and the Lerman Breast Cancer Worry Scales, to assess LCS-related beliefs and lung cancer-related worry. We examined associations between these factors and LDCT completion using 2-sample t tests and chi-square tests. Results: Among 447 eligible individuals, 411 participated in the survey (71% from racial/ethnic minoritized groups), of whom 339 (82%) completed the initial LDCT. Almost half believed that they were at risk for lung cancer in their lifetime, and >90% believed that LCS would help find lung cancer early. Higher self-efficacy scores and lower perceived barriers scores were associated with LDCT completion (P=.002 and P=.004, respectively). Perceived risk and benefit scores were not associated with LDCT completion. Individuals who did not complete the first LDCT were more likely to note fear of lung problems (33% vs 18%; P<.001), stigma related to lung cancer (33% vs 17%; P=.008), and worry affecting mood (77% vs 64%; P=.02). Conclusions: In a diverse, real-world LCS population, most patients believed that LCS facilitates early detection of lung cancer; however, approximately 20% did not complete the initial LDCT. Perceived fear, stigma, and negative emotional responses to a potential lung cancer diagnosis were associated with lower LDCT completion rates. These findings offer insight into potentially modifiable factors and future interventions to improve LCS uptake among eligible individuals.

Background Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC). Osimertinib in combination with chemotherapy beyond osimertinib progression may minimize CNS progression. Method In this retrospective analysis, patients with advanced EGFR mutation positive NSCLC and brain metastases who received platinum-based chemotherapy (PbChT) after disease progression on osimertinib were enrolled. The primary endpoint was real-world CNS progression-free survival (rwCNS-PFS) between patients who received PbChT with and without osimertinib continuation. Secondary endpoints included competing risk analysis of CNS progression and incidence of salvage radiotherapy to brain. Results A total of 101 patients were analyzed, out of which, 39 (39%) continued osimertinib with chemotherapy (OSI+ cohort) and 62 (61%) received chemotherapy alone (OSI- cohort). Median rwCNS-PFS was significantly longer in the OSI+ cohort (9.0 months, 95% CI 6.6-11.4) than the OSI- cohort (5.7 months, 95% CI 4.6-6.9) (HR 0.37, 95% CI 0.18-0.76, p=0.007). This remained significant after adjustment for EGFR mutation, line of osimertinib treatment, prior radiotherapy to brain, and CNS progression on osimertinib monotherapy. Estimated probability of CNS progression at 6 months was 5.6% in OSI+ cohort versus 20.9% in OSI- cohort. Incidence of salvage radiotherapy to brain was lower in the OSI+ cohort (15%) compared to OSI- cohort (24%). Conclusion In patients with EGFR mutation positive NSCLC and brain metastases, continuing osimertinib with chemotherapy after progression on osimertinib significantly reduced risk of CNS progression. Prospective studies are warranted to define the optimal treatment strategy for this patient population. Microabstract This retrospective study analyzed the risk of central nervous system (CNS) progression of patients with advanced EGFR mutation positive NSCLC and brain metastases who received platinum-based chemotherapy after disease progression on osimertinib. Real world CNS progression-free survival was significantly reduced in patients who continued osimertinib with chemotherapy compared to those who received chemotherapy alone (HR 0.37, p=0.007), which remained significant after multivariate analysis. Incidence of salvage radiotherapy was also lower in patients who continued osimertinib with chemotherapy. In patients with EGFR mutation positive NSCLC and brain metastases, continuing osimertinib beyond progression with chemotherapy reduces risk of CNS progression.

High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer. We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic regression modeling was performed to estimate adjusted odds ratios according to patient characteristics. Among 1,998 patients included in the study, 167 (8%) developed grade ≥3 CIPN. Grade ≥3 CIPN was associated with higher body mass index (BMI) (P = .01), sex (7% for men vs 10% for women; P = .005), age (11% for ≥65 years vs 7% for <65 years; P < .001), chemotherapy regimen (P = .01), and greater number treatment cycles (P < .001). In a multivariate model, regimens featuring higher doses of paclitaxel or cisplatin, greater number of chemotherapy cycles, female sex, greater age, and higher BMI remained independently associated with grade ≥3 CIPN. High-grade CIPN is associated with chemotherapy type and exposure, female sex, greater age, and elevated BMI. Given the ongoing use of cytotoxic agents in established and new (eg, antibody-drug conjugates) treatment regimens, these findings have implications for patient monitoring and treatment selection.

PURPOSE:The COVID-19 pandemic disrupted normal mechanisms of health care delivery and facilitated the rapid and widespread implementation of telehealth technology. As a result, the effectiveness of virtual health care visits in diverse populations represents an important consideration. We used lung cancer screening as a prototype to determine whether subsequent adherence differs between virtual and in-person encounters in an urban, safety-net health care system. METHODS:We conducted a retrospective analysis of initial low-dose computed tomography (LDCT) ordered for lung cancer screening from March 2020 through February 2023 within Parkland Health, the integrated safety-net provider for Dallas County, TX. We collected data on patient characteristics, visit type, and LDCT completion from the electronic medical record. Associations among these variables were assessed using the chi-square test. We also performed interaction analyses according to visit type. RESULTS:Initial LDCT orders were placed for a total of 1,887 patients, of whom 43% were female, 45% were Black, and 17% were Hispanic. Among these orders, 343 (18%) were placed during virtual health care visits. From March to August 2020, 79 of 163 (48%) LDCT orders were placed during virtual visits; after that time, 264 of 1,724 (15%) LDCT orders were placed during virtual visits. No patient characteristics were significantly associated with visit type (in-person v virtual) or LDCT completion. Rates of LDCT completion were 95% after in-person visits and 97% after virtual visits (P = .13). CONCLUSION:In a safety-net lung cancer screening population, patients were as likely to complete postvisit initial LDCT when ordered in a virtual encounter as in an in-person encounter.

Background Lung cancer screening (LCS) is indicated exclusively for older individuals with substantial tobacco use, a risk factor not only for lung cancer but also for other malignancies, cardiovascular disease, and chronic obstructive pulmonary disease. Because LCS trial populations are commonly regarded as healthier than the broader LCS-eligible population, the real-world mortality rate among individuals undergoing LCS represents a key consideration in LCS implementation. Methods We performed a retrospective, observational cohort study of individuals for whom LCS was ordered between March 2017 and December 2022 in an integrated safety-net healthcare system. Demographic characteristics and Charlson comorbidity index were obtained from the medical record. Dates and causes of death were captured from the medical record and National Death Index. We compared mortality according to patient characteristics using Cox proportional hazard ratios. Results A total of 1598 patients (mean age 62 years, 43% female, 45% Black, 18% Hispanic) were included in the analysis, of whom 60% had moderate and 20% severe comorbidity; 91% of patients were current smokers. With a median follow-up of 31.3 months, 93 patients (6%) had died. For patients without a date of death, 55% had an encounter in the healthcare system within 3 months of data collection. Mortality was significantly associated with age (HR 1.06; 95% CI, 1.02-1.11; P = .01), but not with patient sex, race, comorbidity, smoking status, or LCS completion. Conclusions Despite substantial comorbidity burden, short-term mortality is low in a diverse, real-world LCS population, suggesting potential for benefit from screening and early detection of lung cancer.

False-positive results from low-dose computed tomography (LDCT)-based lung cancer screening can result in unnecessary follow-up tests, increased patient anxiety, and higher healthcare costs. We evaluated the prevalence of false-positive LDCT results and assessed factors associated with these LDCT results within an integrated, urban safety-net healthcare system serving a diverse and underserved population. Design: Retrospective cohort study. Electronic health records data from Parkland Health, an integrated safety-net provider in Dallas, Texas (January 1, 2017-May 31, 2022), with a 1-year follow-up period through May 31, 2023. False-positive LDCT was defined as positive screen (lung RADS 3, 4A, 4B or 4X) followed by a negative completed work-up or no diagnosis of lung cancer after 12-month follow-up. Univariable and multivariable logistic regression models were used to assess the associations between patient characteristics (patient age, sex, race/ethnicity, preferred language, insurance status, comorbidity score, smoking status and smoking pack-years) and a false-positive LDCT. A total of 2525 LDCTs were included from 2029 patients. Of these, lung cancer was diagnosed in 12 patients (0.6%), and 394 (19.4%) were classified as false-positive. Median age was 62 years, 59% were men, 49% were non-Hispanic Black, 16% were Hispanic, and the median pack-years were 40. In both univariable and multivariable analyses, age was significantly associated with false positive LDCT results. Patients aged 65-70 years (OR=1.81, 95% CI: 1.06-3.10) and >70 years (OR=2.02, 95% CI: 1.15-3.54) had higher odds of false-positive results compared to those aged 50-54 years. In our integrated safety-net healthcare system, approximately one in 5 patients had a false-positive LDCT result, and age was a significant contributor. Patients aged 65 years and older were more likely to experience false-positive findings, suggesting that age-related factors may influence the diagnostic accuracy of LDCT. Future studies are needed to replicate these findings and further minimize unnecessary follow-up interventions, particularly in older populations. Rutu Rathod, Urooj Wahid, Asha Kandathil, Mary Gwin, Sheena Bhalla, Song Zhang, Andrea Semlow, Vijaya Natchimuthu, Sarah Malone, George Oliver, David H. Johnson, Megan A. Mullins, David Gerber, Rasmi Nair. Factors influencing false positive low-dose computed tomography-based lung cancer screening in an urban, safety-net system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7408.

Background: Although low-dose, CT -based lung cancer screening (LCS) can decrease lung cancer mortality in high-risk individuals, the process may be complex and pose challenges to patients, particularly those from minority underinsured and uninsured populations. We conducted a randomized controlled trial of telephone-based navigation for LCS within an integrated, urban, safety-net health care system. Patients and Methods: Patients eligible for LCS were randomized (1:1) to usual care with or without navigation at Parkland Health in Dallas, Texas. The primary endpoint was completion of the first 3 consecutive steps in a patient 's LCS process. We explored differences in completion of LCS steps between navigation and usual care groups, controlling for patient characteristics using the chi-square test. Results: Patients (N = 447) were randomized to either navigation (n = 225) or usual care (n = 222). Mean patient age was 62 years, 46% were female, and 69% were racial/ethnic minorities. There was no difference in completion of the first 3 steps of the LCS algorithm between arms (12% vs 9%, respectively; P = .30). For ordered LCS steps, completion rates were higher among patients who received navigation (86% vs 79%; P = .03). The primary reason for step noncompletion was lack of order placement. Conclusions: In this study, lack of order placement was a key reason for incomplete LCS steps. When orders were placed, patients who received navigation had higher rates of completion. Clinical team education and enhanced electronic health record processes to simplify order placement, coupled with patient navigation, may improve LCS in safety-net health care systems.

Background: Recent modifications to low-dose CT (LDCT)-based lung cancer screening guidelines increase the number of eligible individuals, particularly among racial and ethnic minorities. Because these populations disproportionately live in metropolitan areas, we analyzed the association between travel time and initial LDCT completion within an integrated, urban safety-net health care system. Methods: Using Esri's StreetMap Premium, OpenStreetMap, and the r5r package in R, we determined projected private vehicle and public transportation travel times between patient residence and the screening facility for LDCT ordered in March 2017 through December 2022 at Parkland Memorial Hospital in Dallas, Texas. We characterized associations between travel time and LDCT completion in univariable and multivariable analyses. We tested these associations in a simulation of 10,000 permutations of private vehicle and public transportation distribution. Results: A total of 2,287 patients were included in the analysis, of whom 1,553 (68%) completed the initial ordered LDCT. Mean age was 63 years, and 73% were underrepresented minorities. Median travel time from patient residence to the LDCT screening facility was 17 minutes by private vehicle and 67 minutes by public transportation. There was a small difference in travel time to the LDCT screening facility by public transportation for patients who completed LDCT versus those who did not (67 vs 66 min, respectively; P =.04) but no difference in travel time by private vehicle for these patients (17 min for both; P=.67). In multivariable analysis, LDCT completion was not associated with projected travel time to the LDCT facility by private vehicle (odds ratio, 1.01; 95% CI, 0.82-1.25) or public transportation (odds ratio, 1.14; 95% CI, 0.89-1.44). Similar results were noted across travel-type permutations. Black individuals were 29% less likely to complete LDCT screening compared with White individuals. Conclusions: In an urban population comprising predominantly underrepresented minorities, projected travel time is not associated with initial LDCT completion in an integrated health care system. Other reasons for differences in LDCT completion warrant investigation.

Importance Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC. Objective To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice. Design, Setting, and Participants A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023. Exposure Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy). Main Outcomes and Measures Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death. Results A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%). Conclusions and Relevance In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.

Supplementary Methods, Tables 1-3, Figure 1 from A Risk Variant in an miR-125b Binding Site in BMPR1B Is Associated with Breast Cancer Pathogenesis

Supplementary Figure from Genetic Linkage of Prostate Cancer Risk to the Chromosome 3 Region Bearing <i>FHIT</i>

Supplementary Figure from Genetic Linkage of Prostate Cancer Risk to the Chromosome 3 Region Bearing FHIT

Supplementary Figure 1 Legend from Inhibition of Epidermal Growth Factor Receptor Signaling Elevates 15-Hydroxyprostaglandin Dehydrogenase in Non–Small-Cell Lung Cancer

Low-dose computed tomography-based lung cancer screening represents a complex clinical undertaking that could require multiple referrals, appointments, and time-intensive procedures. These steps may pose difficulties and raise concerns among patients, particularly minority, under-, and uninsured populations. The authors implemented patient navigation to identify and address these challenges. They conducted a pragmatic randomized controlled trial of telephone-based navigation for lung cancer screening in an integrated, urban safety-net health care system. Following standardized protocols, bilingual (Spanish and English) navigators educated, motivated, and empowered patients to traverse the health system. Navigators made systematic contact with patients, recording standardized call characteristics in a study-specific database. Call type, duration, and content were recorded. Univariable and multivariable multinomial logistic regression was performed to investigate associations between call characteristics and reported barriers. Among 225 patients (mean age 63 years, 46% female, 70% racial/ethnic minority) assigned navigation, a total of 559 barriers to screening were identified during 806 telephone calls. The most common barrier categories were personal (46%), provider (30%), and practical (17%). System (6%) and psychosocial (1%) barriers were described by English-speaking patients, but not by Spanish-speaking patients. Over the course of the lung cancer screening process, provider-related barriers decreased 80% (P = 0.008). The authors conclude that patients undergoing lung cancer screening frequently report personal and health care provider-related barriers to successful participation. Barrier types may differ among patient populations and over the course of the screening process. Further understanding of these concerns may increase screening uptake and adherence. Clinical Trial Registration number: (NCT02758054).

Supplementary Figures 1-3 from Thioredoxin-1 Modulates Transcription of Cyclooxygenase-2 via Hypoxia-Inducible Factor-1α in Non–Small Cell Lung Cancer