3079 Background: Preclinical and translational studies demonstrate that KRAS-mutant NSCLC has a unique metabolic dependence on de novo fatty acid synthesis, mediated by fatty acid synthase (FASN) and downstream lipid metabolism pathways that support saturated fatty acid production, enabling rapid tumor growth, survival, and resistance to lipid peroxidation. TVB-2640 is an orally bioavailable and selective FASN inhibitor that blocks the β-ketoacyl reductase step of fatty acid synthesis and has demonstrated antitumor activity in KRAS mutant NSCLC models. Methods: This single-arm trial (NCT03808558) enrolled patients with previously treated, advanced KRAS mutant NSCLC. Eligible patients had progressed on prior platinum-based chemotherapy (100%) and immune checkpoint inhibition (95%), had measurable disease by RECIST v1.1, ECOG performance status 0–1, and adequate organ function. One patient had received prior KRAS directed therapy. TVB-2640 100 mg/m 2 (equivalent to two to four 50-mg tablets) was administered orally once daily in continuous 28-day cycles. Exploratory correlative analyses included 11 C-acetate PET, plasma lipidomics, sebaceous lipid profiling, and quality-of-life measures. Results: Among 18 enrolled patients, the median age was 69 years, 12 (67%) were male, 14 (78%) were white and 13 (72%) had a history of smoking. Median number of prior lines of therapy was 4. The most common KRAS mutations were G12V (44%), G12C (17%), and G12D (17%). No patients had a radiographic response, 7 (39%) had stable disease, 9 (50%) had disease progression, and 2 (11%) were non-evaluable. Five patients (28%) had radiographic shrinkage of target lesions but did not achieve partial response due to the magnitude of decrease (n = 3) or progression of non-target lesions (n = 2). Median progression-free survival was 1.8 months (95% CI, 1.7-1.8 months). Overall, 84% of patients had adverse events (AE). Most common AEs were xerostomia (50%), dry skin (44%), and fatigue (39%). Most common grade ≥ 3 AEs (44%) were fatigue, dermatological toxicities, xerostomia, ocular toxicities and anemia (11% each). Conclusions: Single-agent FASN inhibition with TVB-2640 in heavily pretreated KRAS mutant NSCLC did not meet the primary endpoint of response. Since FASN is a downstream effector of mutant KRAS, combination regimens with KRAS inhibitors can be considered as a future approach in NSCLC. Ongoing correlative studies may further inform the use of this agent. Despite not meeting its primary endpoint, this clinical trial highlights a novel therapy targeting energy metabolism in lung cancer. Clinical trial information: NCT03808558 .

This survey study investigates patient experiences and preferences regarding the electronic communication of cancer diagnoses.

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.

Introduction Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer. Methods Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pretreatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons. Results A total of 187 patients with NSCLC (Black, 19; White, 168) were included in the analysis. Compared with White patients, Black patients had greater comorbidity (median Charlson Comorbidity Index 5 versus 3; p = 0.04) and were more likely to have received previous chemotherapy (79% versus 47%; p = 0.03). Black patients had significantly lower levels of CCL23 and CCL27 and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1b, CXCL16, and IFN-γ (all p < 0.05, false discovery rate < 0.1). Black patients also exhibited greater populations of nonclassical CD16+ monocytes, NKT-like cells, CD4+ cells, CD38+ monocytes, and CD57+ gamma delta T cells (all p < 0.05). Conclusions Black and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous proinflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.

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 While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.Methods We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.Results Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3+ lymphocytes, CD8+ effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels. In irAE cases, we identified distinct baseline proinflammatory gene signatures, including markedly higher expression of IL1B and CXCL8 in monocytes and CXCR3, TNF, and IFNG in T/NK cells. TNF signaling was the most enriched pathway, while immunosuppressive genes SIGLEC7 and CXCR4 were downregulated. Following ICI initiation, these patients exhibited an enhanced shift toward an activated and inflammatory immune phenotype, including monocyte reprogramming characterized by upregulation of IL18 and elevated gene expression levels of CXCL10. Conversely, post-treatment levels of CXCL8 were decreased in irAE patients. Notably, in patients who did not develop clinically significant irAE, we identified increased baseline abundance of a TGFBIhigh myeloid cluster enriched in immunosuppressive markers such as STAB1. In addition, patients without irAE exhibited upregulation of TNF and AIRE, accompanied by distinct myeloid protumorigenic reprogramming.Conclusions A pre-existing activated, autoimmune-like proinflammatory state drives the development of irAE during ICI therapy through three key axes: increased plasmablast/ANA, heightened interferon-gamma/CXCL10/CXCR3 axis, and amplified TNF signaling. These findings may serve as potential peripheral immune biomarkers for predicting irAE and provide biological insights into the mechanisms governing and mitigating irAE.

358 Background: The 21st Century Cures Act Information Blocking Rule, enacted in April 2021, mandates the immediate release of all medical test results to patients through electronic health portals. While this policy enhances access to and exchange of health information, it has also raised concerns about the unintended effects of disclosing life-altering diagnoses—such as cancer—prior to patient-clinician communication. To better understand the patient perspective, we examined the experiences and communication preferences of individuals within a contemporary oncology cohort. Methods: Patients first diagnosed with cancer between January 2019 and December 2023 at an academic cancer center were invited to participate in a brief online survey assessing demographics, cancer history, use of the electronic patient portal (MyChart), and their experiences learning about their cancer diagnosis. We analyzed associations between these factors and the method by which patients received their cancer diagnosis, as well as their preferences for future communication, using Chi-square and T-tests. Results: Of 14,566 surveys delivered, 2,596 responses (18%) were received, of which 2,267 (87%) were complete. Half of the respondents were female, and the median age was 68 years (IQR, 61-74). The majority (63%) of patients were diagnosed with cancer after 2020, and 43% reported using MyChart at least once per week. Most respondents (84%) first learned of their cancer diagnosis through an in-person visit, televisit, or phone call (“clinician first”) rather than initially through the portal. Receiving a cancer diagnosis through MyChart was more common among younger patients ( P < 0.001), those who utilized the portal more frequently ( P = 0.006), and women ( P = 0.03). When asked about the future, 75% of patients preferred to receive a new cancer diagnosis first from a clinician. Respondents who preferred to receive this information immediately via MyChart were more likely to be men ( P < 0.001) and to report higher portal utilization ( P < 0.001). Patient age, educational level, and year of cancer diagnosis were not associated with communication preferences. Among the 163 patients who received an initial cancer diagnosis via MyChart, 73 (45%) preferred to receive future cancer diagnoses from a clinician. Conclusions: Most patients previously diagnosed with cancer preferred to receive a new cancer diagnosis from a clinician rather than immediately via the patient portal. Future interventions and policies that align the delivery of sensitive test results with patient preferences are essential.

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.

Background:In non-small cell lung cancer (NSCLC), programmed death-ligand 1 (PD-L1) expression has moderate ability to predict immune checkpoint inhibitor (ICI) benefit. In clinical practice, PD-L1, a cell surface protein, cannot be characterized in currently available blood-based tests such as circulating tumor DNA assays. To understand the biologic effects of PD-L1 more fully and evaluate whether blood-based tests could provide insight into its expression, we determined the association between PD-L1 expression and systemic immune parameters. Methods:We collected pre- and post-treatment (6-week) peripheral blood samples in patients with NSCLC treated with ICI. Using multiplex panels and cytometry by time of flight (CyTOF), we analyzed specimens for baseline and post-treatment changes in cytokines, autoantibodies, and immune cell populations. We determined the association between case characteristics, immune parameters, and tumor PD-L1 expression (categorized as <1%, 1-49%, and ≥50%) using Chi-square, one-way analysis of variance (ANOVA), and Kruskal-Wallis tests, accounting for multiple comparisons. Results:A total of 119 patients were included in the analysis, of whom 41 (34%) had PD-L1 expression <1%; 44 (37%), 1-49%; and 34 (29%), ≥50%. PD-L1 expression was not associated with any demographic, tumor, or treatment characteristics. Among 39 cytokines evaluated, baseline levels of macrophage migration inhibitory factor (MIF) were significantly greater in high PD-L1 positive cases. Among 124 autoantibodies included in the analysis, three (anti-aggrecan, -proteoglycan, and -nucleosome) demonstrated significantly greater post-ICI treatment increases in cases with higher PD-L1 expression. In PD-L1 positive cases, baseline abundance of natural killer T (NKT) cells (P=0.001) and activated monocytes (P=0.04) were significantly lower, while post-treatment increases in mature natural killer (NK) cells were significantly greater (P=0.006). Conclusions:NSCLC PD-L1 expression is associated with few systemic immune parameters, suggesting that effects on anti-tumor immunity may occur predominantly in the tumor microenvironment and that blood-based assays are unlikely to provide meaningful surrogates of this biomarker.

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:Under-represented populations may have higher smoking rates and face greater risk of lung cancer. We examined perceptions of lung cancer risk and smoking behaviors in an urban safety-net lung cancer screening (LCS) population. Methods:We conducted surveys of English- and Spanish-speaking individuals undergoing first-time low-dose computed tomography (LDCT). Current smoking was defined as one or more cigarettes within the past month. We characterized smoking behavior according to the transtheoretical model of health behavior change. Results were analyzed by Chi-square test, Fisher's exact test, and multivariable logistic regression models. Results:Among 447 invited individuals, 411 (92%) participated in the survey, of whom 53% were Black, 18% were Hispanic, 56% reported income below the federal poverty level, 62% had graduated high school, and 79% were current smokers. Seventy percent reported some degree of worry about developing lung cancer, with 40% perceiving they were at risk in the next 10 years. In multivariable analysis, recent quit attempts were significantly associated with older age, Black race, perceived lung cancer risk in the next ten years, and level of worry about developing lung cancer. Specifically, individuals perceiving personal lung cancer risk were less likely to have made a recent quit attempt (OR 0.47; P = 0.04), while those reporting a lot of worry about developing lung cancer were more likely to have attempted to quit in the prior 12 months (OR 3.81; P = 0.001). Men (OR 1.71; P = 0.03) and Hispanic individuals (OR 3.87 compared to Black individuals; P < 0.001) were more likely to perceive personal risk of lung cancer. When grouped according to health behavior change (precontemplation/contemplation, preparation, action, maintenance), smoking behavior was not associated with level of worry about lung cancer (P = 0.46). Conclusions:In an urban, safety-net LCS population, current smoking rates are high and perceived lung cancer risk varies by numerous demographic characteristics. While most individuals reported worry about lung cancer, which correlated with past quit attempts, this concern is not associated with overall current smoking behavior. Given disparities in smoking rates and lung cancer risk, a nuanced understanding of factors affecting smoking behaviors may optimize cessation interventions in under-represented populations.

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.

INTRODUCTION:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer. PATIENTS AND METHODS:In a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection. RESULTS:Among patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (P = .002). CONCLUSIONS:In a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical.

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.

PURPOSE:Consolidative durvalumab, an anti-programmed death ligand 1 (PDL1) immune checkpoint inhibitor, administered after concurrent chemoradiation improves outcomes of patients with locally advanced non-small cell lung cancer (NSCLC) without substantially increasing toxicities. We studied a chemotherapy-free regimen of thoracic radiation therapy (RT) with concurrent and consolidative durvalumab. METHODS AND MATERIALS:This single-arm phase 2 trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints. Participants received 2 cycles of durvalumab (1500 mg every 4 weeks) concurrently with thoracic RT (60 Gy in 30 fractions), followed by up to 13 cycles of consolidative durvalumab. RESULTS:After 10 patients were enrolled, the trial was closed because of poor clinical outcomes. With a median follow-up of 12 months, 5 patients had disease progression and 8 patients died. Six patients experienced 15 treatment-related, grade ≥3 events, including 1 grade 4 acute kidney injury during consolidation and 2 fatal pulmonary events. One fatal pulmonary event occurred during the concurrent phase in an active smoker; the other occurred after the first cycle of consolidative durvalumab. The primary endpoint of progression-free survival at 12 months was 20% (50% for PDL1≥1% vs 0% for PDL1 unavailable or <1%). Median overall survival was not reached, 10.5 months, and 7 months, for PDL1 ≥1%, <1%, and unavailable, respectively. CONCLUSIONS:In PDL1 unselected stage III NSCLC, thoracic RT plus concurrent and consolidative durvalumab is associated with high-grade toxicity and early disease progression.

BACKGROUND:Although low dose computed tomography (LDCT)-based lung cancer screening (LCS) can decrease lung cancer-related mortality among high-risk individuals, it remains an imperfect and substantially underutilized process. LDCT-based LCS may result in false-positive findings, which can lead to invasive procedures and potential morbidity. Conversely, current guidelines may fail to capture at-risk individuals, particularly those from under-represented minority populations. To address these limitations, numerous biomarkers have emerged to complement LDCT and improve early lung cancer detection.CONTENT:This review focuses primarily on blood-based biomarkers, including protein, microRNAs, circulating DNA, and methylated DNA panels, in current clinical development for LCS. We also examine other emerging biomarkers-utilizing airway epithelia, exhaled breath, sputum, and urine-under investigation. We highlight challenges and limitations of biomarker testing, as well as recent strategies to integrate molecular strategies with imaging technologies.SUMMARY:Multiple biomarkers are under active investigation for LCS, either to improve risk-stratification after nodule detection or to optimize risk-based patient selection for LDCT-based screening. Results from ongoing and future clinical trials will elucidate the clinical utility of biomarkers in the LCS paradigm.

This cohort study among patients with cancer examines changes in the time from posting of test results in the electronic health record to patient viewing in the patient portal before and after implementation of the 21st Century Cures Act.