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Background: Uptake of new systemic therapy treatments among patients with advanced non-small cell lung cancer (NSCLC) occurred rapidly after FDA approval. Few studies have characterized the association of these therapies on survival in community settings. We assessed survival by type of systemic therapy received among patients diagnosed with advanced NSCLC who were treated in community-based settings., Methods: In this retrospective cohort, patients diagnosed with de novo stage IV NSCLC between March 2012 and December 2020 were followed through December 31, 2021. Survival was ascertained with restricted mean survival time from treatment receipt through 12 and 60 months and compared by RMST differences adjusting for demographic and tumor characteristics. Trends in one-year survival probabilities were assessed using joinpoint regression., Results: Of 945 patients receiving systemic therapy, 46% received cytotoxic chemotherapy (Chemo-Only), 15% bevacizumab +/- Chemo, 22% immunotherapy +/- Chemo, and 16% targeted therapies. Median days from diagnosis to treatment ranged from 32 to 42. Compared to those receiving Chemo-Only, patients receiving immunotherapy +/- Chemo survived 1.4 months longer [95% confidence interval (CI): 0.5 to 2.3 months; P=0.002] and 3.2 months longer (95% CI: -1.4 to 7.9 months; P=0.18) through 12 and 60 months follow-up, respectively. Relative to those receiving Chemo-Only, patients receiving targeted therapies survived 1.6 months longer (95% CI: 0.7 to 2.5 months; P<0.001) and 5.5 months longer (95% CI: 0.7 to 10.4 months; P=0.02) through 12 and 60 months follow-up. One-year survival significantly increased from 30% to 59% between 2012 and 2020 (P=0.007)., Conclusions: We found patients receiving targeted therapies and immunotherapy +/- Chemo survived longer than those on Chemo-Only. One-year survival probabilities significantly increased between 2012 and 2020. Additional research is needed to better understand the potential benefits and harms, including patient adverse events and financial toxicity., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-749/coif). N.M.C. reports funding from NIH/NCI (R50CA251966, and UM1CA221939), grants from Pfizer (Award #86341) paid to her institution, and Kaiser Permanente Colorado (RNG212404). Andrea Burnett-Hartman reports funding from NIH/NCI (UM1CA221939) and grants from Biodesix. R.T.G. reports funding from NIH/NCI (UM1CA221939) and serves in an unpaid role on the Governing Board of the Health Care Systems Research Network. S.A.H. reports funding from NIH/NCI (UM1CA221939) and serves in an unpaid role on the Governing Board of the Health Care Systems Research Network. Christine Neslund-Dudas reports funding from NIH/NCI (UM1CA221939), grant from Genentech, and owns stock in Pfizer, Gilead, and Viatris. K.A.R. reports funding from NIH/NCI (UM1CA221939), research support from Pfizer and AstraZeneca paid to her institution, personal fees as a scientific advisor to Merck, Honoraria from MJH Life Sciences to present at a conference, and travel costs from MJH Life Sciences to present at a conference. A.V. reports funding from NIH/NCI (UM1CA221939), research support from Precyte, Inc., Optellum Ltd., NCCN, MagArray, the Gordon and Betty Moore Foundation, the Lungevity Foundation, and Delfi Diagnostics paid to his institution, personal consulting fees from Johnson & Johnson, and participates on the Data Safety Monitoring or Advisory Boards of Intuitive Surgical and Delfi Diagnostics. D.P.R. reports funding from NIH/NCI (UM1CA221939, R01CA260889), the Gordon and Betty Moore Foundation (Award # 9908), the Patient Centered Outcomes Institute (Award # PCS-1403-2653) paid to her institution, and Kaiser Permanente Colorado (RNG212404), and receives salary support paid to her institution, for work outside of this study from Pfizer. The other authors have no conflicts of interest to declare., (Copyright © 2025 AME Publishing Company. All rights reserved.)

Objectives: Text messaging could be effective for determining patient eligibility for lung cancer screening (LCS). We explored people's willingness to share their tobacco use history via text message among diverse groups., Study Design: Cross-sectional survey., Methods: In 2020, we conducted a cross-sectional survey asking respondents about cellular phone usage, smoking habits, sociodemographic characteristics, and the likelihood of responding to a text message from their health care provider's office about tobacco use. We used χ² and analysis of variance tests for comparisons., Results: Among 745 respondents, 90% used text messaging casually. Overall, 54% never smoked, 33% currently smoked, and 13% previously smoked. Six percent were LCS eligible, and 20% used both cigarettes and e-cigarettes (dual users). Current smokers were significantly younger, less likely to be female, and more likely to use text messaging. LCS-eligible respondents were older and less likely to have a high income. Dual users were younger, less likely to report female gender and live in rural areas, and more likely to have a college education and high income. Most respondents (83%) indicated they were likely to respond to text message inquiries regarding smoking status. Middle-aged respondents (mean age, 37 years) were significantly more willing to report smoking status than younger or older respondents (91% vs 84% and 84%, respectively). Respondents with no college education (83% vs 88%) or with a low income vs a middle or high income (81% vs 86% and 88%, respectively) were significantly less willing to report smoking status via text messages., Conclusions: Text messaging showed promise for evaluating smoking history and for simplifying the process of identifying LCS-eligible individuals. However, achieving equity in identifying eligibility for LCS requires the implementation of multimodal strategies.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Population models of cancer reflect the overall US population by drawing on numerous existing data resources for parameter inputs and calibration targets. Models require data inputs that are appropriately representative, collected in a harmonized manner, have minimal missing or inaccurate values, and reflect adequate sample sizes. Data resource priorities for population modeling to support cancer health equity include increasing the availability of data that 1) arise from uninsured and underinsured individuals and those traditionally not included in health-care delivery studies, 2) reflect relevant exposures for groups historically and intentionally excluded across the full cancer control continuum, 3) disaggregate categories (race, ethnicity, socioeconomic status, gender, sexual orientation, etc.) and their intersections that conceal important variation in health outcomes, 4) identify specific populations of interest in clinical databases whose health outcomes have been understudied, 5) enhance health records through expanded data elements and linkage with other data types (eg, patient surveys, provider and/or facility level information, neighborhood data), 6) decrease missing and misclassified data from historically underrecognized populations, and 7) capture potential measures or effects of systemic racism and corresponding intervenable targets for change., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Declines in the prevalence of cigarette smoking, advances in targeted therapies, and implementation of lung cancer screening have changed the clinical landscape for lung cancer. The proportion of lung cancer deaths is increasing in those who have never smoked cigarettes. To better understand contemporary patterns in survival among patients with lung cancer, a comprehensive evaluation of factors associated with survival, including differential associations by smoking status, is needed., Methods: Patients diagnosed with lung cancer between January 1, 2010, and September 30, 2019, were identified. We estimated all-cause and lung cancer-specific median, 5-year, and multivariable restricted mean survival time (RMST) to identify demographic, socioeconomic, and clinical factors associated with survival, overall and stratified by smoking status (never, former, and current)., Results: Analyses included 6813 patients with lung cancer: 13.9% never smoked, 54.2% formerly smoked, and 31.9% currently smoked. All-cause RMST through 5 years for those who never, formerly, and currently smoked was 32.1, 25.9, and 23.3 months, respectively. Lung cancer-specific RMST was 36.3 months, 30.3 months, and 26.0 months, respectively. Across most models, female sex, younger age, higher socioeconomic measures, first-course surgery, histology, and body mass index were positively associated, and higher stage was inversely associated with survival. Relative to White patients, Black patients had increased survival among those who formerly smoked., Conclusions: We identify actionable factors associated with survival between those who never, formerly, and currently smoked cigarettes. These findings illuminate opportunities to address underlying mechanisms driving lung cancer progression, including use of first-course treatment, and enhanced implementation of tailored smoking cessation interventions for individuals diagnosed with cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility., Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry., Design, Setting, and Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry., Outcome Measurements and Statistical Analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness., Results and Limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10 -4 )., Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry., Patient Summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Authors aimed to calculate the percentage up-to-date with testing in the context of lung cancer screening across 5 healthcare systems and evaluate differences according to patient and health system characteristics., Methods: Lung cancer screening‒eligible individuals receiving care within the five systems in the Population-based Research to Optimize the Screening Process Lung consortium from October 1, 2018 to September 30, 2019 were included in analyses. Data collection was completed on June 15, 2021; final analyses were completed on April 1, 2022. Chest computed tomography scans and patient characteristics were obtained through electronic health records and used to calculate the percentage completing a chest computed tomography scan in the previous 12 months (considered up-to-date). The association of patient and healthcare system factors with being up-to-date was evaluated with adjusted prevalence ratios and 95% CIs using log-binomial regression models., Results: There were 29,417 individuals eligible for lung cancer screening as of September 30, 2019; 8,333 (28.3%) were up-to-date with testing. Those aged 65-74 years (prevalence ratio=1.19; CI=1.15, 1.24, versus ages 55-64), those with chronic obstructive pulmonary disease (prevalence ratio=2.05; CI=1.98, 2.13), and those in higher SES census tracts (prevalence ratio=1.22; CI=1.16, 1.30, highest quintile versus lowest) were more likely to be up-to-date. Currently smoking (prevalence ratio=0.91; CI=0.88, 0.95), having a BMI ≥30 kg/m 2 (prevalence ratio=0.83; CI=0.77, 0.88), identifying as Native Hawaiian or other Pacific Islander (prevalence ratio=0.79; CI=0.68, 0.92), and having a decentralized lung cancer screening program (prevalence ratio=0.77; CI=0.74, 0.80) were inversely associated with being up-to-date., Conclusions: The percentage up-to-date with testing among those eligible for lung cancer screening is well below up-to-date estimates for other types of cancer screening, and disparities in lung cancer screening participation remain., (Copyright © 2023 American Journal of Preventive Medicine. All rights reserved.)

Introduction/background: Systemic treatment for advanced non-small cell lung cancer (NSCLC) is shifting from platinum-based chemotherapy to immunotherapy and targeted therapies associated with improved survival in clinical trials. As new therapies are approved for use, examining variations in use for treating patients in community practice can generate additional evidence as to the magnitude of their benefit., Patients and Methods: We identified 1,442 patients diagnosed with de novo stage IV NSCLC between 3/1/2012 and 12/31/2020. Patient characteristics and treatment patterns are described overall and by type of first- and second-line systemic therapy received. Prevalence ratios estimate the association of patient and tumor characteristics with receipt of first-line therapy., Results: Within 180 days of diagnosis, 949 (66%) patients received first-line systemic therapy, increasing from 53% in 2012 to 71% in 2020 (p = 0.0004). The proportion of patients receiving first-line immunotherapy+/-chemotherapy (IMO) increased from 14%-66% (p<0.0001). Overall, 380 (26%) patients received both first- and second-line treatment, varying by year between 16%-36% (p = 0.18). The proportion of patients receiving second-line IMO increased from 13%-37% (p<0.0001). Older age and current smoking status were inversely associated with receipt of first-line therapy. Higher BMI, receipt of radiation, and diagnosis year were positively associated with receipt of first-line therapy. No association was found for race, ethnicity, or socioeconomic status., Conclusion: The proportion of advanced NSCLC patients receiving first- and second-line treatment increased over time, particularly for IMO treatments. Additional research is needed to better understand the impact of these therapies on patient outcomes, including short-term, long-term, and financial toxicities., Microabstract: Systemic treatment for non-small cell lung cancer (NSCLC) is shifting from platinum-based therapies to immunotherapy and targeted therapies. Using de novo stage IV NSCLC patients identified from 4 healthcare systems, we examine trends in systemic therapy. We saw an increase in the portion of patients receiving any systemic therapy and a sharp increase in the proportion of patients receiving immunotherapy., Competing Interests: Declaration of Competing Interest NMC and DPR report research support from Pfizer paid to their institution, outside of the submitted work. KAR reports research support from Pfizer and AstraZeneca paid to her institution and personal fees as a scientific advisor to Merck, all outside of the submitted work. ABH reports research support from Biodesix, paid to her institution outside of the submitted work. AV reports personal fees as a scientific advisor to the Lung Cancer Initiative at Johnson & Johnson and grants to his institution from MagArray, Inc., Broncus Medical, Inc., and Precyte, Inc. outside of the submitted work. AV is an advisory board member of the Lungevity Foundation (unpaid). CND reports research support from Genentech paid to her institution, outside of the submitted work. All other authors reported no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Chronic obstructive pulmonary disease (COPD) is a known comorbidity for lung cancer independent of smoking history. Quantitative computed tomography (qCT) imaging features related to COPD have shown promise in the assessment of lung cancer risk. We hypothesize that qCT features from the lung, lobe, and airway tree related to the location of the pulmonary nodule can be used to provide informative malignancy risk assessment., Methods: A total of 183 qCT features were extracted from 278 individuals with a solitary pulmonary nodule of known diagnosis (71 malignant, 207 benign). These included histogram and airway characteristics of the lungs, lobe, and segmental paths. Performances of the least absolute shrinkage and selection operator (LASSO) regression analysis and an ensemble of neural networks (ENN) were compared for feature set selection and classification on a testing cohort of 49 additional individuals (15 malignant, 34 benign)., Results: The LASSO and ENN methods produced different feature sets for classification with LASSO selecting fewer qCT features (7) than the ENN (17). The LASSO model with the highest performing training area under the curve (AUC) (0.80) incorporated automatically extracted features and reader-measured nodule diameter with a testing AUC of 0.62. The ENN model with the highest performing AUC (0.77) also incorporated qCT and reader diameter but maintained higher testing performance AUC (0.79)., Conclusions: Automatically extracted qCT imaging features of the lung can be informative of the differentiation between individuals with malignant pulmonary nodules and those with benign pulmonary nodules, without requiring nodule segmentation and analysis., (JCOPDF © 2021.)

Smoking burdens are greatest among underserved patients. Lung cancer screening (LCS) reduces mortality among individuals at risk for smoking-associated lung cancer. Although LCS programs must offer smoking cessation support, the interventions that best promote cessation among underserved patients in this setting are unknown. This stakeholder-engaged, pragmatic randomized clinical trial will compare the effectiveness of four interventions promoting smoking cessation among underserved patients referred for LCS. By using an additive study design, all four arms provide standard "ask-advise-refer" care. Arm 2 adds free or subsidized pharmacologic cessation aids, arm 3 adds financial incentives up to $600 for cessation, and arm 4 adds a mobile device-delivered episodic future thinking tool to promote attention to long-term health goals. We hypothesize that smoking abstinence rates will be higher with the addition of each intervention when compared with arm 1. We will enroll 3,200 adults with LCS orders at four U.S. health systems. Eligible patients include those who smoke at least one cigarette daily and self-identify as a member of an underserved group (i.e., is Black or Latinx, is a rural resident, completed a high school education or less, and/or has a household income <200% of the federal poverty line). The primary outcome is biochemically confirmed smoking abstinence sustained through 6 months. Secondary outcomes include abstinence sustained through 12 months, other smoking-related clinical outcomes, and patient-reported outcomes. This pragmatic randomized clinical trial will identify the most effective smoking cessation strategies that LCS programs can implement to reduce smoking burdens affecting underserved populations. Clinical trial registered with clinicaltrials.gov (NCT04798664). Date of registration: March 12, 2021. Date of trial launch: May 17, 2021.

The ubiquitin proteasome system has been validated as a target of cancer therapies evident by the US FDA approval of anticancer 20S proteasome inhibitors. Deubiquitinating enzymes (DUBs), an essential component of the ubiquitin proteasome system, regulate cellular processes through the removal of ubiquitin from ubiquitinated-tagged proteins. The deubiquitination process has been linked with cancer and other pathologies. As such, the study of proteasomal DUBs and their inhibitors has garnered interest as a novel strategy to improve current cancer therapies, especially for cancers resistant to 20S proteasome inhibitors. This article reviews proteasomal DUB inhibitors in the context of: discovery through rational design approach, discovery from searching natural products and discovery from repurposing old drugs, and offers a future perspective.

Cadmium is a known carcinogen that has been implicated in prostate cancer, but how it affects prostate carcinogenesis in humans remains unclear. Evidence from basic science suggests that cadmium can bind to the androgen receptor causing endocrine disruption. The androgen receptor is required for normal prostate development and is the key driver of prostate cancer progression. In this study, we examined the association between cadmium content and androgen receptor protein expression in prostate cancer tissue of African American (N = 22) and European American (N = 30) men. Although neither overall tumor cadmium content (log transformed) nor androgen receptor protein expression level differed by race, we observed a race-cadmium interaction with regard to androgen receptor expression (P = 0.003) even after accounting for age at prostatectomy, smoking history, and Gleason score. African American men had a significant positive correlation between tumor tissue cadmium content and androgen receptor expression (Pearson correlation = 0.52, P = 0.013), while European Americans showed a non-significant negative correlation between the two (Pearson correlation = -0.19, P = 0.31). These results were unchanged after further accounting for tissue zinc content or dietary zinc or selenium intake. African American cases with high-cadmium content (>median) in tumor tissue had more than double the androgen receptor expression (0.021 vs. 0.008, P = 0.014) of African American men with low-cadmium level. No difference in androgen receptor expression was observed in European Americans by cadmium level (high 0.015 vs. low 0.011, P = 0.30). Larger studies are needed to confirm these results and if upheld, determine the biologic mechanism by which cadmium increases androgen receptor protein expression in a race-dependent manner. Our results suggest that cadmium may play a role in race disparities observed in prostate cancer., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Rationale: Lung cancer screening registries can monitor screening outcomes and improve quality of care., Objectives: To describe nascent lung cancer screening programs and share efficient data collection approaches for mandatory registry reporting in four integrated health care systems of the National Cancer Institute-funded Cancer Research Network., Methods: We documented the distinctive characteristics of lung cancer screening programs, and we provide examples of strategies to facilitate data collection and describe early challenges and possible solutions. In addition, we report preliminary data on use and outcomes of screening with low-dose computed tomography at each of the participating sites., Results: Programs varied in approaches to confirming patient eligibility, ordering screening low-dose computed tomographic scans, and coordinating follow-up care. Most data elements were collected from structured fields in electronic health records, but sites also made use of standardized order templates, local procedure codes, identifiable hashtags in radiology reports, and natural language processing algorithms. Common challenges included incomplete documentation of tobacco smoking history, difficulty distinguishing between scans performed for screening versus diagnosis or surveillance, and variable adherence with use of standardized templates. Adherence with eligibility criteria as well as the accuracy and completeness of data collection appeared to depend at least partly on availability of personnel and other resources to support the successful implementation of screening., Conclusions: To maximize the effectiveness of lung cancer screening, minimize the burden of data collection, and facilitate research and quality improvement, clinical workflow and information technology should be purposefully designed to ensure that patients meet eligibility criteria and receive appropriate follow-up testing.

Purpose/objectives: To evaluate use of a CD-ROM titled Completing a Life among patients diagnosed with serious illnesses for comfort level with content and ease of computer use., Design: A prospective pilot study collected a convenience sample of 50 people diagnosed with life-limiting illnesses during a six-month period., Setting: The hematology/oncology department of a large healthcare system located in a metropolitan area in the midwestern United States., Sample: Convenience sample of 50 patients diagnosed with life-limiting illnesses. Of the patients enrolled (age range = 38-93 years), 72% were female, 68% were Caucasian, 50% were diagnosed with breast cancer or nonsolid tumors, and 40% were newly diagnosed., Methods: Subjects viewed the CD-ROM and completed pre- and post-intervention surveys., Main Research Variables: Comfort level with educational media, comfort level of information viewed, and areas of CD-ROM viewed compared to age and stage of illness., Findings: Ninety percent of patients reported that they were somewhat or very comfortable with the CD-ROM as a learning tool, and ease of use was rated at 98%. Patients' comfort level with the material increased from 76% to 90% after they viewed the CD-ROM., Conclusions: The pilot study suggests that the Completing a Life CD-ROM can be used with patients facing serious or life-limiting illnesses as an additional resource tool for information., Implications for Nursing: Nurses typically provide the bulk of educational material for their patients. With limited resources available regarding management of life-limiting illnesses, this resource may provide an excellent addition to resources currently available.