Mortality In High-risk Individuals Research Articles

ASSOCIATION BETWEEN LOW LEVEL BLOOD LEAD EXPOSURE AND MORTALITY IN US ADULTS WITH CHRONIC KIDNEY DISEASE

Objective: This study aimed to explore the association between blood lead and both chronic kidney disease (CKD) and cardiovascular and all-cause mortality among participants with or without CKD in the US adults. Design and method: Date from the National Health and Nutrition Examination Survey (2007-20018) was used and all participants were followed up regularly until December 31, 2019. CKD was defined as an eGFR <60 ml/min/1.73 m2 and/or a urine albumin and creatinine ratio >= 30 mg/g. Logistic regression models were constructed to explore the associations between blood lead and CKD. The Kaplan–Meier analysis with a log-rank test was performed to estimate the cumulative incidence of mortality between groups. Cox proportional-hazards models were used to explore the associations between blood lead and cardiovascular and all-cause mortality. Results: Totally, this study enrolled 22,951 participants, including 4,078 CKD participants. Multivariable logistic regression analysis showed that higher level of blood lead (>=1.82 vs. <0.73) was associated with the increased risk of CKD (OR:1.35, 95% CI: 1.13–1.62, p=0.001). During a mean follow-up duration of 85.21±43.58 months, a total of 2,139 all-cause mortality and 525 cardiovascular mortality were recorded. In multivariable Cox model, compared with the lowest quartiles, highest blood lead level (>=1.82 vs. < 0.73) was associated with a higher risk of cardiovascular mortality (HR:3.36, 95% CI: 1.32–8.53) and all-cause mortality (HR:1.85, 95% CI: 1.18–2.90) in participants with CKD. Conclusions: In conclusion, in this US cohort, low level blood lead exposure may also be a predictive factor for CKD, and increasing blood lead concentrations significantly contributed to enhanced risk of cardiovascular and all-cause mortality in CKD patients. Hence, the reduce of blood lead exposure may reduce risk of mortality in high-risk individuals with CKD.

Barriers to Completing Low Dose Computed Tomography Scan for Lung Cancer Screening

IntroductionAnnual low-dose computed tomography (LDCT) screening has been shown to reduce lung cancer mortality in high-risk individuals by detecting the disease at an earlier stage. This study aims to assess the barriers to completing LDCT in a cohort of patients who were determined eligible for lung cancer screening (LCS). MethodsWe performed a single institution, mixed methods, cross-sectional study of patients who had a LDCT ordered from July to December 2022. We then completed phone surveys with patients who did not complete LDCT to assess knowledge, attitude, and perceptions toward LCS. ResultsWe identified 380 patients who met inclusion criteria, including 331 (87%) who completed LDCT and 49 (13%) who did not. Patients who completed a LDCT and those who did not were similar regarding age, sex, race, primary language, household income, body mass index, median pack years, and quit time. Positive predictors of LDCT completion were: meeting USPSTF guidelines (97.9% vs 81.6%), being married (58.3% vs 44.9%), former versus current smokers (55% vs 41.7%), personal history of emphysema (60.4% vs 42.9%), and family history of lung cancer (13.9% vs 4.1%) (all P < .05). Of the patients who participated in the phone survey, only 7% of respondents thought they were high risk for developing lung cancer despite attending a shared decision-making visit and only 10% wanted to re-schedule their LDCT. ConclusionThere exist barriers to completing LDCT even after patients are identified as eligible and complete a shared decision-making visit secondary to knowledge barriers, misperceptions, and patient disinterest.

Public Heterogeneous Preferences for Low-Dose Computed Tomography Lung Cancer Screening Service Delivery in Western China: A Discrete Choice Experiment.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) is an efficient method that can reduce lung cancer mortality in high-risk individuals. However, few studies have attempted to measure the preferences for LDCT LCS service delivery. This study aimed to generate quantitative information on the Chinese population's preferences for LDCT LCS service delivery. The general population aged 40 to 74 in the Sichuan province of China was invited to complete an online discrete choice experiment (DCE). The DCE required participants to answer 14 discrete choice questions comprising five attributes: facility levels, facility ownership, travel mode, travel time, and out-of-pocket cost. Choice data were analyzed using mixed logit and latent class logit (LCL) models. The study included 2529 respondents, with 746 (29.5%) identified as being at risk for lung cancer. Mixed logit model (MLM) analysis revealed that all five attributes significantly influenced respondents' choices. Facility levels had the highest relative importance (44.4%), followed by facility ownership (28.1%), while out-of-pocket cost had the lowest importance (6.4%). The at-risk group placed relatively more importance on price and facility ownership compared to the non-risk group. LCL model identified five distinct classes with varying preferences. This study revealed significant heterogeneity in preferences for LCS service attributes among the Chinese population, with facility level and facility ownership being the most important factors. The findings underscore the need for tailored strategies targeting different subgroup preferences to increase screening participation rates and improve early detection outcomes.

Liquid biopsy-based early tumor and minimal residual disease detection: New perspectives for cancer predisposition syndromes.

Genetic predisposition is one of the major measurable cancer risk factors. Affected patients have an enhanced risk for cancer and require life-long surveillance. However, current screening measures are mostly invasive and only available for certain tumor types. Particularly in hereditary cancer syndromes, liquid biopsy, in addition to monitoring therapy response and assessing minimal residual disease, holds great potential for surveillance at the precancerous stage and potentially even diagnostics. Exploring these options and future clinical translation could help reduce cancer risk and mortality in high-risk individuals and enhance patients' adherence to tailored surveillance protocols.

Results from Lung Cancer Screening Outreach Utilizing a Mobile CT Scanner in an Urban Area

IntroductionLung cancer screening using low-dose (LD) CT reduces lung cancer–specific and all-cause mortality in high-risk individuals, although significant barriers to screening remain. We assessed the outreach of a mobile lung cancer screening program to increase screening accessibility and early detection of lung cancer. MethodsWe placed a mobile CT unit in a high-traffic area in New York City and offered free screening to all eligible patients. Characteristics of the mobile screening cohort were compared with those of our hospital-based screening cohort. ResultsBetween December 9, 2019, and January 30, 2020, a total of 216 patients underwent mobile LDCT screening. Compared with the hospital-based screening cohort, mobile screening participants were significantly more likely to be younger, be uninsured, and have lower smoking intensity and were less likely to meet 2013 US Preventive Services Task Force guidelines (but would meet their 2021 guidelines) and self-identify as White race and Hispanic ethnicity. Asian New Yorkers were substantially underrepresented in both hospital and mobile screening cohorts, compared with their level of representation in New York City. Two patients were diagnosed with lung cancer and were treated. Potentially clinically significant non–lung cancer findings were identified in 28.2%, most commonly moderate-severe coronary artery calcification and emphysema. ConclusionsMobile LDCT screening is useful and effective in detecting lung cancer and other significant findings and may engage a distinct high-risk patient demographic. Disproportionately low screening rates among certain high-risk populations highlight the imperative of implementing strategies aimed at understanding health behaviors and access barriers for diverse populations. Effective care-navigation services, facilitating high-quality care for all patients, are critical.

Clinician’s Ability to Identify Non-Melanoma Skin Cancer on 3D-Total Body Photography Sectors that Were Initially Identified during In-Person Skin Examination with Dermoscopy

Introduction: Non-melanoma skin cancer (NMSC) is a cause of significant morbidity and mortality in high-risk individuals. Total body photography (TBP) is currently used to monitor melanocytic lesions in patients with high risk for melanoma. The authors examined if three-dimensional (3D)-TBP could be useful for diagnosis of NMSC. Methods: Patients (n = 129; 52 female, 77 male) with lesions suspicious for NMSC who had not yet had a biopsy underwent clinical examination followed by examination of each lesion with 3D-TBP Vectra^®WB360 (Canfield Scientific, Parsippany, NJ, USA) and dermoscopy. Results: The 129 patients had a total of 182 lesions. Histological examination was performed for 158 lesions; the diagnoses included basal cell carcinoma (BCC; n = 107), squamous cell carcinoma (SCC; n = 27), in-situ SCC (n = 15). Lesions were located in the head/neck region (n = 138), trunk (n = 21), and limbs (n = 23). Of the 182 lesions examined, 12 were not visible on 3D-TBP; reasons for not being visible included location under hair and on septal of nose. Two lesions appeared only as erythema in 3D-TBP but were clearly identifiable on conventional photographs. Sensitivity of 3D-TBP was lower than that of dermoscopy for BCC (73% vs. 79%, p = 0.327), higher for SCC (81% vs. 74%, p = 0.727), and lower for in-situ SCC (0% vs. 33%, p = 125). Specificity of 3D-TBP was lower than that of dermoscopy for BCC (77% vs. 82%, 0.581), lower for SCC (75% vs. 84%, p = 0.063), and higher for in-situ SCC (97% vs. 94%, p = 0.344). Diagnostic accuracy of 3D-TBP was lower than that of dermoscopy for BCC (75% vs. 80%), lower for SCC (76% vs. 82%), and lower for in-situ SCC (88% vs. 89%). Lesion location was not associated with diagnostic confidence in dermoscopy (p = 0.152) or 3D-TBP (p = 0.353). If only lesions with high confidence were included in the calculation, diagnostic accuracy increased for BCC (n = 27; sensitivity 85%, specificity 85%, diagnostic accuracy 85%), SCC (n = 10; sensitivity 90%, specificity 80%, diagnostic accuracy 83%), and for in-situ SCC (n = 2; sensitivity 0%, specificity 100%, diagnostic accuracy 95%). Conclusion: Diagnostic accuracy appears to be slightly lower for 3D-TBP in comparison to dermoscopy. However, there is no statistically significant difference in the sensitivity and specificity of 3D-TBP and dermoscopy for NMSC. Diagnostic accuracy increases, if only lesions with high confidence are included in the calculation. Further studies are necessary to determine if 3D-TBP can improve management of NMSC.

Development of a MEK inhibitor, NFX-179, as a chemoprevention agent for squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although cSCC contributes to substantial morbidity and mortality in high-risk individuals, deployment of otherwise effective chemoprevention of cSCC is limited by toxicities. Our systematic computational drug repurposing screen predicted that selumetinib, a MAPK (mitogen-activated protein kinase) kinase inhibitor (MEKi), would reverse transcriptional signatures associated with cSCC development, consistent with our genomic analysis implicating MEK as a chemoprevention target. Although systemic MEKi suppresses the formation of cSCC in mice, systemic MEKi can cause severe adverse effects. Here, we report the development of a metabolically labile MEKi, NFX-179, designed to potently and selectively suppress the MAPK pathway in the skin before rapid metabolism in the systemic circulation. NFX-179 was identified on the basis of its biochemical and cellular potency, selectivity, and rapid metabolism upon systemic absorption. In our ultraviolet-induced cSCC mouse model, topical application of NFX-179 gel reduced the formation of new cSCCs by an average of 60% at doses of 0.1% and greater at 28 days. We further confirmed the localized nature of these effects in an additional split-mouse randomized controlled study where suppression of cSCC was observed only in drug-treated areas. No toxicities were observed. NFX-179 inhibits the growth of human SCC cell lines in a dose-dependent manner, and topical NFX-179 application penetrates human skin and inhibits MAPK signaling in human cSCC explants. Together, our data provide a compelling rationale for using topical MEK inhibition through the application of NFX-179 gel as an effective strategy for cSCC chemoprevention.

Prevalence of hospitalized women at high-risk for developing lung cancer

ABSTRACT Background Lung cancer screening with low-dose computer tomography (CT) has been shown to reduce the lung cancer mortality in high-risk individuals by 20%. Despite the proven mortality benefit, the utilization of lung cancer screening among high-risk populations remains low. Objective This study explores the prevalence of high-risk population for developing lung cancer among hospitalized women and evaluates the screening behavior toward other common cancers during a hospital stay. Methods This is a cross-sectional study in which 248 cancer-free hospitalized women aged 50–75 years who reported current or prior smoking were enrolled during hospital admission at an academic center. A bedside survey was conducted to collect socio-demographic, cancer screening behavior, and medical comorbidities for the study patients. Unpaired t-test and Chi-square tests were used to compare characteristics and common cancer screening behavior by lung cancer risk stratification. Results Forty-three percent of the hospitalized women were at intermediate to high-risk for developing lung cancer risk. Intermediate to high-risk women were more likely to be older, Caucasian, retired, or with a disability, and had higher comorbidity burden as compared to the low-risk group. Women at low and intermediate to high risk were equally non-adherent with breast (35% vs 31%, p = 0.59) and colorectal (32% vs 24%, p = 0.20) cancers screening guidelines. Only 38% of women from the intermediate to the high-risk group had a CT chest within the last year. Conclusion The study’s findings suggest that almost half of the hospitalized women who report current or past smoking are at high-risk for developing lung cancer.

Patient navigation for lung cancer screening in an urban safety-net system: A pragmatic randomized clinical trial.

10577 Background: Although low-dose computed tomography (LDCT)-based lung cancer screening (LCS) can decrease lung cancer mortality in high-risk individuals, it may be a complex and time-intensive process that poses challenges to patients, particularly those from minority, under- and uninsured populations. We conducted a pragmatic randomized controlled trial of telephone-based navigation for LCS within an integrated, urban safety-net healthcare system (Parkland Health, Dallas, Texas). Methods: Patients eligible for LCS based on United States Preventive Services Task Force 2013 Guidelines were randomized (1:1) to usual care with or without phone-based navigation. Following a structured protocol, navigators made systemic contact with patients to provide appointment reminders, share information and resources, assess barriers to LCS, and address smoking cessation. The primary endpoint was completion of the first three consecutive steps (eg, 3 annual LDCTs or LDCT, other imaging, biopsy) in a patient’s LCS process. We also explored differences in completion of LCS steps in navigation and usual care groups according to patient characteristics using chi-square test. Results: Patients (n=447) were randomized to phone-based navigation (n=225) or usual care (n=222) between February 2017 and February 2019. Mean patient age was 62 years, 46% were female, and 69% were racial-ethnic minorities. There was no significant difference in completion of the first three steps of the LCS algorithm (12 vs. 9%; P=0.3) between arms. Completion of LCS steps was not impacted by navigation among different subgroups, including age (&lt;65 vs. ≥65 years), gender (male vs. female), race/ethnicity (non-hispanic white vs. racial minorities), and comorbidity status (Charlson Comorbidity Index &lt;5 vs. ≥5). A key reason for step non-completion was lack of order placement. In the navigation arm, 368 of expected 675 steps (55%) were ordered, and in the usual care arm, 344 of expected 666 steps (52%) were ordered. Despite low three-step completion rates overall, the majority (&gt;75%) of LCS algorithm steps were completed when ordered by their clinical team(Table). In exploratory univariable analysis, completion rates for ordered steps were 86% for navigation and 79% for usual care ( P=0.03). Conclusions: In this study, lack of order placement was a key reason for incomplete LCS steps. When orders were placed, navigated patients had higher rates of completion. Clinical team education and enhanced EHR processes to simplify order placement, coupled with patient navigation, may increase LCS uptake and completion in safety-net healthcare systems. Clinical trial information: NCT02758054 . [Table: see text]

Abstract A021: Development of a novel MEK inhibitor, NFX-179, as a chemoprevention agent for squamous cell carcinoma

Abstract Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer comprising at least 20% of all non-melanoma skin cancers. While cSCC contributes to significant morbidity and mortality in high-risk individuals, deployment of otherwise effective chemoprevention of cSCC is limited by toxicities. To help address this, we conducted a systematic computational drug repositioning screen which predicted that selumetinib, an FDA-approved MEK inhibitor (MEKi), would reverse transcriptional signatures associated with cSCC development. This is consistent with our genomic analysis implicating ETS2, a transcription factor in the canonical RAS/RAF/MEK/ERK Mitogen-Activated Protein Kinase (MAPK) pathway, as an upstream regulator of cSCC development. Therefore, as a key regulator of the MAPK pathway, we reasoned MEK would be a viable chemopreventive target. Although systemic MEK inhibition suppresses the formation of cSCC in mice, systemic MEKi administration causes significant adverse effects, including diarrhea, peripheral edema, cardiomyopathy and retinal toxicity. Here, we report the development of a topically formulated, metabolically labile, novel MEKi, NFX-179, designed to potently and selectively suppress the MAPK pathway in the skin prior to rapid metabolism in the systemic circulation. NFX-179 was identified from a targeted drug discovery effort based on its biochemical and cellular potency, selectivity, and rapid metabolism upon systemic absorption. In our UV-induced cSCC mouse model, topical application of NFX- 179 gel reduced the formation of new cSCCs by an average of 60% at doses of 0.1% and greater at 28 days. No systemic or skin toxicities were observed in this model. Furthermore, we conducted a second split-mouse randomized controlled study in which NFX-179 0.5% gel was applied to one half of the back and vehicle was applied to the opposite half of each of the UV-irradiated mice. Near complete suppression of cSCC was observed only in the drug-treated area, demonstrating the targeted and dermal effect of the intervention. NFX-179 inhibits the growth of human SCC cell lines in a dose-dependent manner and topical NFX-179 application penetrates human skin and inhibits MAPK signaling in human cSCC explants. Together our data provide compelling rationale for using topical MEK inhibition through application of NFX-179 gel as an effective strategy for cSCC chemoprevention. Citation Format: Kavita Y. Sarin, John Kincaid, Brittney Sell, Jahanbanoo Shahryari, Matthew A. J. Duncton, Elaine Morefield, Wenchao Sun, Omar Chavez-Chiang, Scott R. Plotkin, Gerd G. Kochendoerfer, Peter Fenn, Christopher Powala, Kenneth Y. Tsai. Development of a novel MEK inhibitor, NFX-179, as a chemoprevention agent for squamous cell carcinoma [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A021.

P1.04-03 Independent Validation of the Maisonneuve Lung Cancer Risk Model to Optimize Screening Interval in High-risk Individuals

Lung cancer screening represents a valid tool to reduce lung cancer mortality in high-risk individuals due to the ability to detect early lung cancer in a phase where curable treatments have best choice of success. Different risk models have been developed and validated to identify the best target population taking into consideration different epidemiological variables, but few have focused on the identification of the best screening interval for a particular individual. The aim of this study it to validate in a subset of the COSMOS II study, the risk model built by Maisonneuve et al.

Adverse reactions to COVID-19 vaccines: A practical approach.

COVID‐19‐related mortality in high‐risk individuals is substantial and current treatment options are limited. There is convincing evidence that the COVID‐19 vaccines reduce the severity of infection and prevent deaths. Three COVID‐19 vaccines are approved in the United Kingdom with many more in development. There are limited data on the triggers and mechanisms of anaphylaxis to these vaccines. We review the potential allergenic compounds in the COVID‐19 vaccines and describe an innovative allergy support model for the vaccination hubs that allows most patients with severe allergy be immunized. Finally, we propose a practical algorithm for the investigations of anaphylaxis to these vaccines.

A narrative review of lung cancer screening in underserved populations

: Lung cancer screening with low-dose computed tomography (LDCT) is an effective approach for the early detection of lung cancer and the reduction of lung cancer specific mortality in high risk individuals. Despite recommendations for LDCT screening by the National Comprehensive Cancer Network (NCCN) and the United States Preventive Services Task Force, the utilization of LDCT screening in clinical practice has been low. Moreover, significant disparities in the use of LDCT have been described in underserved populations, including African American or black patients, rural patients with limited access to LDCT screening facilities, and other vulnerable patient groups with known risk factors for developing lung cancer. Several patient, provider, and healthcare systems level approaches have been proposed to mitigate lung cancer screening disparities. Such approaches include raising awareness of LDCT screening benefits and the evidence in support of LDCT screening among healthcare providers, educating patients on LDCT screening and optimizing shared decision-making approaches between patients and providers, and expanding patient access to LDCT screening through free and mobile lung cancer screening programs. As lung cancer screening utilization continues to expand in clinical practice, it will be critical to continue investigating the trends, causes, and outcomes of LDCT screening disparities in underserved populations.

Challenges With Colorectal Cancer Family History Assessment—Motivation to Translate Polygenic Risk Scores Into Practice

Challenges With Colorectal Cancer Family History Assessment—Motivation to Translate Polygenic Risk Scores Into Practice

P1.11-14 SGLT2 Is a Diagnostic and Therapeutic Target for Early-Stage Lung Adenocarcinoma

Early diagnosis of lung adenocarcinoma (LUAD) is crucial. The National Lung Screening Trial showed a 20% reduction in lung cancer mortality in high risk individuals using low-dose helical computed tomography (CT). CT is highly sensitive for detecting lung nodules, but is limited by low specificity, especially for LUAD. On CT, LUAD may appear as solid or subsolid nodules. Most subsolid nodules are not cancer, and many will remain stable or resolve; however, subsolid lesions can represent premalignancy or adenocarcinoma in situ. These lesions in the early spectrum of LUAD may persist for months to years before transforming into invasive disease. As a result, current standard of care is to follow these patients with CT imaging to monitor these indeterminate lesions for radiologic signs of malignant progression. The identification of novel biomarkers to predict the malignant potential of these nodules at their initial identification is of paramount importance. We have recently discovered that premalignant ad early invasive lesions of the LUAD spectrum rely on sodium-glucose transporter 2 (SGLT2) for glucose uptake, whereas advanced carcinomas up-regulate transporters of the GLUT family. This is consistent with the observation that positron emission tomography (PET) with 2-[18F] fluorodeoxyglucose (FDG), which detects GLUT but not SGLT activity, is a standard tool for staging advanced disease, but has low sensitivity for early-stage LUAD. We measured SGLT2 activity in vivo with the PET tracer methyl-4-[18F] fluorodeoxyglucose (Me4FDG). Me4FDG detects early-stage, FDG-negative LUAD in mouse models and in patients. Importantly, Me4FDG uptake correlates with tumor growth rate in patient-derived LUAD xenografts (fig. 1). Targeting SGLT2 with FDA-approved inhibitors significantly reduces tumor growth and prolongs survival in genetic and patient-derived murine models, confirming an important role of SGLT2 in early-stage LUAD. SGLT2 is a promising biomarker not only to diagnose early-stage tumors by PET imaging, but also to predict response to SGLT2 inhibitors.

Abstract 4224: SGLT2 is a diagnostic target for early stage lung adenocarcinoma

Abstract Lung cancer is the leading cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis and treatment are essential; however, there are no targeted diagnostic and therapeutic approaches for early LUAD. An important hallmark of cancer is the increased glucose uptake via GLUT transporters. GLUT activity is imaged in cancer by positron emission tomography (PET) with 2-[18F] fluorodeoxyglucose (FDG). FDG PET is a standard tool for staging advanced lung cancer, but has low sensitivity for early-stage LUAD. This is considered a consequence of slow growth and low requirement of glucose. However, we discovered a novel system of metabolic supply not detected by FDG PET: the sodium glucose transporter 2 (SGLT2)1. SGLT2 activity can be measured in vivo with the PET tracer methyl-4-[18F] fluorodeoxyglucose (Me4FDG). We identified high expression of SGLT2 in human lung premalignancy and early-stage LUAD. Me4FDG detects early-stage, FDG-negative LUAD in mouse models. Targeting SGLT2 with FDA-approved inhibitors significantly reduces tumor growth and prolongs survival in genetic and patient-derived murine models, confirming an important role of SGLT2 in early-stage LUAD2. The reliance of early stage LUAD on SGLT2 opens exciting diagnostic and therapeutic opportunities. The National Lung Screening Trial showed a 20% reduction in lung cancer mortality in high risk individuals using low-dose helical computed tomography (CT). CT is highly sensitive for detecting lung nodules, but is limited by low specificity, especially for LUAD. On CT, LUAD may appear as solid or subsolid nodules. Most subsolid nodules are not cancer, and many will remain stable or resolve; however, subsolid lesions can represent premalignant lesions or adenocarcinoma in situ. These lesions in the early spectrum of LUAD may persist for months to years before transforming into invasive disease. As a result, current standard of care is to follow these patients with CT imaging to monitor these indeterminate lesions for radiologic signs of malignant progression. The identification of novel biomarkers to predict the malignant potential of these nodules at their initial identification is of paramount importance. 1Scafoglio et al. Proc Natl Acad Sci U S A 2015;112(30):E4111-4119 2Scafoglio et al. Sci. Transl. Med. 10, eaat5933 (2018) Citation Format: Brendon Villegas, Eva Koziolek, Jie Liu, W. Dean Wallace, David Elashoff, Denise R. Aberle, David B. Shackelford, Jorge R. Barrio, Jane Yanagawa, Steven M. Dubinett, Claudio Scafoglio. SGLT2 is a diagnostic target for early stage lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4224.

Lung Cancer Screening Utilization: A Behavioral Risk Factor Surveillance System Analysis

Lung cancer is the leading cause of cancer-related death in the U.S. The National Lung Screening Trial found that low-dose computed tomography reduced lung cancer mortality in high-risk individuals. As a result, the U.S. Preventive Services Task Force began recommending low-dose computed tomography screening for those at a high risk in 2013. Therefore, it is imperative to continually monitor lung cancer screening uptake. The objective of this study was to determine computed tomography screening uptake across ten states using 2017 Behavioral Risk Factor Surveillance System survey data. In fall 2018, a cross-sectional analysis was performed on survey data from 4,374 low-dose computed tomography-eligible participants, as determined by Task Force recommendations. Weighted percentages were calculated to assess computed tomography screening utilization overall and by state, sociodemographic, and clinical characteristics; Wald chi-squared tests evaluated group differences. Within the study sample, 14.4% of eligible individuals had a computed tomography scan to test for lung cancer within the past 12 months. Significant state-to-state variation was identified (6.5% utilization in Nevada to 18.1% in Florida, p=0.03). Screening utilization was higher among individuals with insurance than among the uninsured (15.2% vs 4.0%, p<0.001), and it was higher among individuals with asthma (22.9% vs 12.9%, p=0.006) or chronic obstructive pulmonary disease (23.7% vs 8.5%, p<0.001) than among those without either condition. Computed tomography screening utilization was higher than in earlier estimates. However, further research is needed to elucidate geographic variation in screening.

Lung cancer screening from the oncologist’s perspective

With the release of the survival results from the NELSON lung cancer screening trial there is now additional evidence that low-dose computed tomography (LDCT) screening leads to a reduction of lung cancer mortality in high-risk individuals. These results clearly show that LDCT screening has to be implemented in daily routine. However some questions like the most efficient screening intervals, duration of screening or the most appropriate participant selection are still not finally answered. This article provides a view on lung cancer screening from an oncologist’s perspective.

Abstract A16: Sodium-dependent glucose transporter 2 is a novel diagnostic and therapeutic target for early-stage lung adenocarcinoma

Abstract Lung cancer claims approximately 160,000 lives in the United States every year, and lung adenocarcinoma (LADC) is the most frequent type. Early diagnosis is crucial; the National Lung Screening Trial showed a 20% reduction in mortality in high-risk individuals screened by computed tomography (CT). However, CT has low specificity in early-stage LADC. In vivo detection of glucose uptake by FDG PET is a standard tool for lung cancer staging, but has low sensitivity in early-stage LADC. Here, we demonstrate that GLUT transporters, responsible for FDG uptake, are expressed in advanced, poorly differentiated LADC, whereas early LADC utilizes a different glucose transport system, the sodium-dependent glucose transporter 2 (SGLT2), that is not detected by FDG. This can be imaged with the novel tracer Me4FDG. We investigated the expression of two different glucose transporters, GLUT1 and SGLT2, in a cohort of 56 human LADC specimens, in patient-derived xenografts, and in a KrasG12D-driven, p53-null genetically engineered mouse model of LADC. We observed a switch in the modality of glucose transport during lung carcinogenesis: SGLT2 was highly expressed in premalignant lesions and well-differentiated LADC, whereas GLUT1 was upregulated in advanced, poorly differentiated lesions. This pattern was observed both in human samples and in murine models. This observation led us to hypothesize that early-stage LADCs are often negative on FDG PET because this imaging modality does not detect the activity of SGLT2, which is expressed in early lesions. Therefore, we performed PET imaging with the tracer Me4FDG, which measures SGLT2 activity, in our mouse model, and observed that Me4FDG accumulated in small nodules that were negative with FDG. We confirmed the functionality of SGLT2 in human LADC by Me4FDG PET in patient-derived xenografts. Finally, we tested the hypothesis that sodium-dependent glucose transport is a critical metabolic supply strategy in the early stages of lung adenocarcinoma development. We performed therapeutic trials in genetically engineered mouse models with the FDA-approved SGLT2 inhibitor canagliflozin, which slowed down tumor progression and prolonged mouse survival, by specifically reducing the proliferation rate of premalignant lesions. In conclusion, Me4FDG PET is a novel diagnostic test to image lung premalignancy and early-stage LADC. We propose that Me4FDG-PET will identify the patients who are likely to respond to SGLT2 inhibition, as a cancer interception strategy to prevent the progression of premalignancy to invasive disease, by blocking the supply of glucose required for proliferation of premalignant lesions. Citation Format: Claudio Scafoglio, Sean T. Bailey, Gihad Abdelhady, Jie Liu, Jane Yanagawa, Aditya Shirali, Dean W. Wallace, Jorge R. Barrio, Ernest M. Wright, Tonya Walser, Steven M. Dubinett, David B. Shackelford. Sodium-dependent glucose transporter 2 is a novel diagnostic and therapeutic target for early-stage lung adenocarcinoma [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A16.

Patient navigation for lung cancer screening among current smokers in community health centers a randomized controlled trial.

Annual chest computed tomography (CT) can decrease lung cancer mortality in high‐risk individuals. Patient navigation improves cancer screening rates in underserved populations. Randomized controlled trial was conducted from February 2016 to January 2017 to evaluate the impact of a patient navigation program on lung cancer screening (LCS) among current smokers in five community health centers (CHCs) affiliated with an academic primary care network. We randomized 1200 smokers aged 55–77 years to intervention (n = 400) or usual care (n = 800). Navigators contacted patients to determine LCS eligibility, introduce shared decision making about screening, schedule appointments with primary care physicians (PCPs), and help overcome barriers to obtaining screening and follow‐up. Control patients received usual care. The main outcome was the proportion of patients who had any chest CT. Secondary outcomes were the proportion of patients contacted, proportion receiving LCS CTs, screening results and number of lung cancers diagnosed. Of the 400 intervention patients, 335 were contacted and 76 refused participation. Of the 259 participants, 124 (48%) were ineligible for screening; 119 had smoked <30 pack‐years, and five had competing comorbidities. Among the 135 eligible participants in the intervention group, 124 (92%) had any chest CT performed. In intention‐to‐treat analyses, 124 intervention patients (31%) had any chest CT versus 138 control patients (17.3%, P < 0.001). LCS CTs were performed in 94 intervention patients (23.5%) versus 69 controls (8.6%, P < 0.001). A total of 20% of screened patients required follow‐up. Lung cancer was diagnosed in eight intervention (2%) and four control (0.5%) patients. A patient navigation program implemented in CHCs significantly increased LCS among high‐risk current smokers.