Pack-year Smoking History Research Articles

Cumulative effect of lifetime smoking history on arterial stiffness and subclinical atherosclerosis in patients with arterial hypertension

Abstract Introduction Although the effect of smoking status on blood pressure (BP) changes is well known an adverse association between cumulative smoke exposure (by pack-years) and functional and structural changes in arteries of patients with high BP has not been consistently demonstrated. Aim of the study was to explore the contributions of cumulative smoke exposure to the vascular consequences of arterial hypertension. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx) and carotid intima media thickness (cIMT) were measured in 485 adults aged less than 60 years old without a history of cardiovascular disease. The cohort was divided into three groups according to office systolic BP (SBP) and diastolic BP (DBP): normal (SBP <130 and DBP <85 mmHg, n=242), high normal (130≤SBP<140 or DBP 85≤DBP<90mmHg, n=96), and hypertension (SBP≥140 or DBP≥90mmHg, n=147). The cohort was subdivided according to pack-years of smoking history as never smokers (0.0 pack-years), light smokers (<20 pack-years), moderate smokers (20-40 pack-years), and heavy smokers (> 40 pack-years). Results The three BP groups had similar age and metabolic parameters (body mass index, fasting blood glucose and LDL-C). Figure shows PWV, AIx and carotid IMT by smoking exposure, stratified by BP level. The lowest PWV level was observed in never smokers with normal BP; whereas heavy smokers with hypertension exhibited the highest PWV. Also of note, heavy smokers with normal BP exhibited comparable PWV to light and never smokers with hypertension. Furthermore, in smokers with more than 20 pack-years tobacco exposure, PWV was higher among patients with high normal BP compared to subjects with normal BP (all P<0.01). In contrast to the monotonic increases in PWV and AIx by BP and pack-years smoking history, carotid IMT was generally similar among BP groups on the basis of cumulative exposure category. This finding may indicate a plateau in subclinical atherosclerotic burden over cumulative tobacco exposure for all BP categories. Conclusion Tobacco cumulative exposure adversely modify the effect of BP on arterial stiffness. Given that most adults who smoke start before the age 18 years, efforts to promote smoking cessation should continue to target younger adults with high BP.BP, tobacco exposure-vascular changes

Acute exacerbation of congestive heart failure following intranasal cocaine use

Background: Most presentations of decompensated congestive heart failure occur in patients diagnosed with pre-existing heart failure. Decompensation presents as progressive dyspnea, abdominal and peripheral congestions, as well as neurological symptoms. It typically occurs following physiological stressors such as infection, arrhythmia, or medical non-adherence. Chronic heart failure may result from cardiovascular comorbid conditions, such as coronary artery disease, valvular disease, and long-standing hypertension. Long term cocaine use also results in adverse cardiovascular health. Cocaine use can augment pre-existing risk factors for both chronic congestive heart failure and acute decompensations - namely, coronary artery disease, congestive heart failure, and peripheral vascular disease. It can also independently pose a cardiovascular risk by causing acute ischemia, vasoconstriction, tachycardia, systolic dysfunction, and cardiac remodeling. The Case: the case of a 49-year-old Caucasian male, who presented with worsening dyspnea on exertion and bilateral peripheral edema extending to his abdomen. His symptoms worsened over the preceding week and began after three consecutive days of intranasal cocaine use. He presented with a background history of congestive heart failure, coronary artery disease, peripheral vascular disease, a 30 pack-year smoking history, and weekly cocaine use for the past 12 years. Conclusion: Cocaine use can lead to decompensation of congestive heart failure in patients with extensive cardiac and vascular disease. Cocaine use can also acutely worsen systolic function and cause demand ischemia, on a background of chronic remodelling and atherosclerotic changes. Patient Consent Obtained: Yes

A Potential Pneumothorax Induced by Immune Checkpoint Inhibitors: A Case Report and Literature Review

Background and Objectives: Immune checkpoint inhibitors (ICIs), which target immune checkpoints in cancer cells, are increasingly used as a mainstay in anticancer treatment. The combination of atezolizumab and bevacizumab is also a first-line treatment for hepatocellular carcinoma (HCC). However, ICIs can cause immune-related adverse events (IrAEs) which range from mild to severe, potentially leading to the need for discontinuing immunotherapy. We report a case of a pneumothorax, a rare side effect caused by IrAEs. Materials and Methods: This paper reports a case of a 78-year-old male HCC patient who developed a recurrent pneumothorax, suspected to be an adverse effect of ICIs. Results: The patient was a current smoker with a 30 pack-year smoking history. Prior to initiating ICIs, a chest CT scan showed mild emphysema and fibrosis attributable to smoking. Following ICI treatment, the patient developed a recurrent pneumothorax. Further tests revealed no underlying cause for the pneumothorax other than the ICIs and smoking, and there were no signs of intrapulmonary metastasis or pneumonitis. Conclusions: When a pneumothorax occurs in a patient undergoing immunotherapy, it is important to consider it as a potential adverse effect of the treatment. Special attention should be given to the possibility that immunotherapy may exacerbate underlying lung conditions. Patients should be advised on the importance of smoking cessation. As there are currently no guidelines for resuming immunotherapy after a pneumothorax, it is crucial to weigh the risks and benefits and consider dose reduction or discontinuation of the medication.

7242 Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) In A Patient With Recurrent Carcinoid

Abstract Disclosure: F. Woron: None. T.L. Anderson: None. P. Madhavan: None. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare generalized proliferation of pulmonary neuroendocrine cells. It is considered to be a pre-invasive lesion for pulmonary carcinoid, a rare neuroendocrine tumor (NET). DIPNECH is thought to be underdiagnosed, as patients can be asymptomatic or present with nonspecific cough and dyspnea, though it is also associated with fibrotic lung changes. Long-term annual surveillance imaging is recommended for due to the potential for development and metastasis of carcinoid tumors. We present a patient with recurrent pulmonary carcinoid later diagnosed with probable DIPNECH based on CT findings. The patient is a 72-year-old female with a prior 15 pack-year smoking history, who initially had a left lower lobe typical carcinoid tumor diagnosed and resected in 2018, with no evidence of lymph node metastasis. The patient’s medical history also includes pulmonary sarcoidosis, adrenal adenoma, thyroid nodule, hiatal hernia, and prediabetes. She has no family history of neuroendocrine tumors. Physical exam showed stable vitals with blood pressure of 112/70 mmHg in the right upper arm, heart rate of 84 bpm, and a body mass index of 39. Physical exam was unremarkable except for thyroid nodularity and obesity. Extensive biochemical evaluation for markers including chromogranin A and 24-hour urine 5-HIAA levels were within normal limits. In 2022, surveillance CT imaging showed a new 9 mm nodule in the right lobe within the bronchus, which was shown to be carcinoid on FNA. She complained of dyspnea and wheezing at this time, which has been managed with an albuterol inhaler. In 2023, PET/CT copper 64 dotatate scan showed a focal area of activity related to the nodule in the superior segment, also identified on recent CT scan, with the nodule measuring approximately 2.05 cm x 1.8 cm with a maximal SUV of 4.2. Interestingly, somatostatin receptor scintigraphy did not show any pick-up in the lung in 2018 or 2022. In 2023, the patient underwent right lower lobe superior segmentectomy after the nodule was found to have increased in size. Pathology showed G1, well-differentiated 1.1 cm typical carcinoid tumor with margins negative for invasive carcinoma. All 18 regional lymph nodes were negative for tumor. Immunohistochemical tests show that the tumor cells were positive for INSM1 and chromogranin with a low Ki-67 proliferation index (<2%), supporting the diagnosis. The patient is currently being monitored by yearly CT imaging and followed by both endocrinology and pulmonology. Given this case, we propose that DIPNECH should be considered as a differential in cases of pulmonary carcinoid, especially recurrent ones. Given that DIPNECH is thought to be underdiagnosed and a precursor for carcinoid associated with fibrotic lung changes, it is essential for this disease to be identified in order for patients to receive appropriate long-term monitoring. Presentation: 6/1/2024

Survival of lung cancer patients according to screening eligibility using Korean Lung Cancer Registry 2014–2016

This study assessed survival for lung cancer patients meeting criteria for the National Lung Cancer Screening Program in Korea launched in 2019 and updated guideline reported by the US Preventive Service Task Force (USPSTF). We assessed all-cause mortality based on the Korean Lung Cancer Registry (KLCR), including lung cancer patients diagnosed in 2014–2016. We compared survival among lung cancer patients eligible for extended USPSTF criteria (age 50–80 years and ≥ 20 pack-years) and those meeting current criteria (age 54–74 years and ≥ 30 pack-years, current or within the past 15 years). The nearest neighbour propensity-score matching was performed to generate a matched set. Kaplan–Meier curves were generated to compare survival among groups; differences in survival were analyzed using the stratified log-rank test. The mortality risk was estimated based on a Cox proportional hazards regression model and the robust standard error was calculated. Of 8110 patients, 37.4% and 24.3% met the extended USPSTF eligibility criteria and National Lung Cancer Screening Program (NLCSP) criteria, respectively. Overall mortality risk was not significantly different between the extended younger age group and the NLCSP group (hazard ratio [HR] [95% confidence interval (CI)]: 0.78 [0.59–1.02]). The extended older age group had a significantly higher mortality risk (HR [95% CI]: 1.41 [1.26–1.58]). Mortality risk was not significantly different between patients who smoked 20–29 pack-years and those who smoked ≥ 30 pack-years (HR [95% CI]: 0.90 [0.79–1.03]). Lung cancer patients aged 50–53 years and those with a 20–29 pack-years smoking history exhibited similar mortality risk to individuals meeting current criteria, while patients aged 75–80 years were at a higher risk of death. Although we verified similar or higher mortality risks in extended subgroups, a careful assessment of the benefits and harms of the screening tests is necessary when contemplating the extension of criteria.

Abstract A145: Race and sex disparities in lung cancer screening and evaluation of alternative identifiers in patients’ electronic medical record to better identify lung cancer screening candidates

Abstract Introduction: The US Preventive Services Task Force (USPSTF) recommends lung cancer screening with a low dose CT scan in patients who are 50 – 80 years old with at least a 20 pack-year smoking history and currently smoke or quit in the last 15 years. Yet, only 5.8 percent of eligible Americans were screened in 2022. We investigated demographic screening patterns and evaluated for alternative identifiers in patients’ electronic medical record (EMR) to identify lung cancer screening candidates at a large and diverse cancer center in Los Angeles. Methods: We examined 607 patients with non-small cell lung cancer (NSCLC) treated at the University of Southern California Norris Comprehensive Care Center or Los Angeles General Medical Center from 2009-2023. EMR data included age of diagnosis, sex, race/ethnicity, smoking history, and stage at diagnosis; for patients with unknown number of pack years (n=25) they counted as not qualified for screening. Identifiers investigated were International Classification of Disease, Tenth Revision (ICD-10) code for chronic obstructive pulmonary disease (COPD), prescription of inhaled steroids, and documented lung cancer history. Fisher’s exact test was used to compare proportion of qualified screeners among groups. Results: 35% (215/607) of patients would have qualified for lung cancer screening according to the USPSTF guidelines, including a greater proportion of males 52% (164/313) versus females 17% (51/293) (p<0.0001). In males, Non-Hispanic Whites (NHW) 59% (55/93) had a greater proportion that would qualify compared to Hispanics 41% (31/75) (p=0.0295). In females, NHW 34% (30/89) had the highest proportion of qualifiers while Asians 6% (6/104) and Hispanics 9% (6/66) had the lowest proportion of qualifiers (p<0.0001). 65% (215/332) of smokers qualified for screening; males had a higher percentage who qualified for screening versus females (164/234, 70% vs. 51/98, 52%, p=0.0024). By race, NHW male smokers had the highest proportion of qualifiers 77% (55/71) while Hispanic women had the lowest proportion of qualifiers 50% (6/12). 27% (89/332) of patients were found to have an ICD-10 code for COPD, including 18% (21/117) had an ICD-10 code for COPD who did not qualify. 19% (63/332) smokers received a prescription for inhaled steroids, including 15% (18/117) of them who didn’t qualify for screening. 12% had a family history of lung cancer (39/332), while 9% (10/117) of these patients didn’t qualify for screening. Conclusion: There were significant race and sex screening disparities among known NSCLC patients including under 10% of Asian and Hispanic females. There were about 10-15% known lung cancer patients who would not have qualified for screening found to have an ICD-10 code for COPD, an inhaled steroids prescription, or documented family history. These alternative identifiers may serve as identifiers for lung cancer screening candidates in the EMR to help address race and sex disparities in screening. Future directions should include simulation of these identifiers in larger patient datasets. Citation Format: Darin Poei, Aubree Mades, Iris Yao, Nick Ahn, Ajay Prasad, Jennifer Tsui, Jacob S Thomas, Jorge J Nieva, Robert Hsu. Race and sex disparities in lung cancer screening and evaluation of alternative identifiers in patients’ electronic medical record to better identify lung cancer screening candidates [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A145.

Association of Smoking Status and Pack Year History With Urinary Urgency Symptoms.

Overactive bladder and its hallmark symptom, urgency, are thought to be multifactorial in pathogenesis. Smoking is a particularly important risk factor to understand because it is modifiable; studies evaluating an association between smoking and urgency have been inconclusive. We therefore sought to rigorously assess the relationship between smoking and urgency in terms of both a temporal and quantitative pack year history of smoking while controlling for other possible confounding factors. Community-based adult women were recruited using the ResearchMatch website to participate in an online survey of bladder health which included questions to assess urgency symptoms, medical comorbidities, and detailed smoking history. Smoking history was studied as the independent variable in three different formulations: smoking status (never vs. former vs. current), continuous pack year history, and categorical pack year history. The outcomes studied included urgency (any urgency in the past 7 days), moderate urgency (urgency at least half the time), and urgency urinary incontinence (UUI). Chi-square tests were performed to detect associations between smoking and these outcomes, and multivariate regression was then performed to control for possible confounders and to help determine the comparative influence of temporality versus quantity of smoking history. In 1720 women who completed the questionnaire, current smoking status was associated with a 23% increase in the risk of experiencing urgency (RR 1.23) and a 78% increase in the risk of experiencing moderate urgency (RR 1.78) relative to never smokers. The risk of experiencing UUI was 40% higher (RR 1.40). Lifetime pack year history was also significantly associated with urgency outcomes, although only in smokers/former smokers who had a 20+ pack year history (RR 1.15, 1.60, and 1.25 for urgency, moderate urgency, and UUI, respectively). The presence of former smoking history was not significantly associated with urgency outcomes, even when controlling for cumulative pack years. This analysis of a large cross-sectional database of women suggests a strong, consistent link between current smoking status and urinary urgency and UUI. By contrast, no increased risk of urgency was attributed to former smoking status. Analysis of pack year history suggests a dose-response relationship wherein ≥ 20 pack years was significantly associated with a higher risk of all urgency outcomes. In models controlling for pack year history, the association of current smoking with urgency remained significant and former smoking remained nonsignificant. Taken together, this supports greater attention being given to the contribution of current smoking to urgency symptoms, and to the need for further longitudinal work to determine if smoking cessation can be a strategy to treat urgency.

Emphysema and lung cancer risk.

With increasing significance of lung cancer screening programs, it is essential to determine the group of participants, who would benefit the most from screening. In our study, we aimed to establish the correlation between lung emphysema and lung cancer risk. The study design was cross-sectional. Low-dose computed tomography (LDCT) scans of 896 subjects from MOLTEST-BIS lung cancer screening program, including 100 subjects with detected lung cancer, were visually evaluated for the presence, type and severity of emphysema. Quantitative emphysema evaluation was performed with Siemens syngo.via Pulmo 3D application. Visually detected presence of centrilobular emphysema (CLE) correlated with male gender (P=0.02), age (P<0.001) and pack-years of smoking (P=0.004), as well as with quantitative assessment of Emphysema Index (EI) (P=0.008), and with emphysema clusters of given size (Clas 1-4) Clas 1, Clas 3 and Clas 4 (P<0.001). Visually assessed severity grade of emphysema correlated with age (P<0.001), pack-years of smoking history (P=0.002) and EI (P<0.001). There was a correlation between lung cancer occurrence and pack-years (P<0.001), age (P<0.001), and presence of CLE (P<0.001) but no correlation with gender (P=0.88) and EI (P=0.32) was found. In the logistic regression model pack-years, age, qualitative severity of CLE and Clas 1 were significant factors correlated with lung cancer occurrence (P<0.001). Qualitative and quantitative emphysema evaluation correlate with each other. Both, presence and severity of CLE correlate with higher incidence of lung cancer. Severity of visually assessed emphysema, age and pack-years of smoking are significant predictors of lung cancer occurrence.

Development and validation of a mortality risk prediction model for chronic obstructive pulmonary disease: a cross-sectional study using probabilistic graphical modelling

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in patients with COPD can be important for disease management strategies. Although all-cause mortality predictors have been developed previously, limited research exists on factors directly affecting COPD-specific mortality. In a retrospective study, we used probabilistic graphs to analyse clinical cross-sectional data (COPDGene cohort), including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data. COPDGene recruited current and former smokers, aged 45-80 years with >10 pack-years smoking history, from across the USA (Phase 1, 11/2007-4/2011) and invited them for a follow-up visit (Phase 2, 7/2013-7/2017). ECLIPSE cohort recruited current and former smokers (COPD patients and controls from USA and Europe), aged 45-80 with smoking history >10 pack-years (12/2005-11/2007). We applied graphical models on multi-modal data COPDGene Phase 1 participants to identify factors directly affecting all-cause and COPD-specific mortality (primary outcomes); and on Phase 2 follow-up cohort to identify additional molecular and social factors affecting mortality. We used penalized Cox regression with features selected by the causal graph to build VAPORED, a mortality risk prediction model. VAPORED was compared to existing scores (BODE: BMI, airflow obstruction, dyspnoea, exercise capacity; ADO: age, dyspnoea, airflow obstruction) on the ability to rank individuals by mortality risk, using four evaluation metrics (concordance, concordance probability estimate (CPE), cumulative/dynamic (C/D) area under the receiver operating characteristic curve (AUC), and integrated C/D AUC). The results were validated in ECLIPSE. Graphical models, applied on the COPDGene Phase 1 samples (n=8610), identified 11 and 7 variables directly linked to all-cause and COPD-specific mortality, respectively. Although many appear in both models, non-lung comorbidities appear only in the all-cause model, while forced vital capacity (FVC %predicted) appears in COPD-specific mortality model only. Additionally, the graph model of Phase 2 data (n=3182) identified internet access, CD4 T cells and platelets to be linked to lower mortality risk. Furthermore, using the 7 variables linked to COPD-specific mortality (forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) ration, FVC %predicted, age, history of pneumonia, oxygen saturation, 6-min walk distance, dyspnoea) we developed VAPORED mortality risk score, which we validated on the ECLIPSE cohort (3-yr all-cause mortality data, n=2312). VAPORED performed significantly better than ADO, BODE, and updated BODE indices in predicting all-cause mortality in ECLIPSE in terms of concordance (VAPORED [0.719] vs ADO [0.693; FDR p-value 0.014], BODE [0.695; FDR p-value 0.020], and updated BODE [0.694; FDR p-value 0.021]); CPE (VAPORED [0.714] vs ADO [0.673; FDR p-value <0.0001], BODE [0.662; FDR p-value <0.0001], and updated BODE [0.646; FDR p-value <0.0001]); 3-year C/D AUC (VAPORED [0.728] vs ADO [0.702; FDR p-value 0.017], BODE [0.704; FDR p-value 0.021], and updated BODE [0.703; FDR p-value 0.024]); integrated C/D AUC (VAPORED [0.723] vs ADO [0.698; FDR p-value 0.047], BODE [0.695; FDR p-value 0.024], and updated BODE [0.690; FDR p-value 0.021]). Finally, we developed a web tool to help clinicians calculate VAPORED mortality risk and compare it to ADO and BODE predictions. Our work is an important step towards improving our identification of high-risk patients and generating hypotheses of potential biological mechanisms and social factors driving mortality in patients with COPD at the population level. The main limitation of our study is the fact that the analysed datasets consist of older people with extensive smoking history and limited racial diversity. Thus, the results are relevant to high-risk individuals or those diagnosed with COPD and the VAPORED score is validated for them. This research was supported by NIH [NHLBI, NLM]. The COPDGene study is supported by the COPD Foundation, through grants from AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion.

OA01.03 Pack-Year Smoking History: An Inadequate and Biased Measure to Determine Lung Cancer Screening Eligibility

OA01.03 Pack-Year Smoking History: An Inadequate and Biased Measure to Determine Lung Cancer Screening Eligibility

Comparing the diagnostic considerations between general practitioners with a special interest in cardiovascular disease and those without in patients with symptoms suggestive of heart failure: a vignette study

BackgroundGeneral practitioners (GPs) specialized in cardiovascular disease (GPSI-CVD) may suspect heart failure (HF) more easily than GPs not specialized in CVD. We assessed whether GPSI-CVD consider investigations aimed at detecting HF more often than other GPs in two clinical scenarios of an older male person with respiratory and suggestive HF symptoms.MethodsIn this vignette study, Dutch GPs evaluated two vignettes. The first involved a 72-year-old man with hypertension and a 30 pack-year smoking history who presented himself with symptoms of a common cold, but also shortness of breath, reduced exercise tolerance, and signs of fluid overload. The second vignette was similar but now the 72-year-old man was known with chronic obstructive pulmonary disease (COPD).GPs could select diagnostic tests from a multiple-choice list with answer options targeted at HF, COPD or exacerbation of COPD, or lower respiratory tract infection. With Pearson Chi-square or Fisher’s exact test differences between the two GP groups were assessed regarding the chosen diagnostic tests.ResultsOf the 148 participating GPs, 25 were GPSI-CVD and 123 were other GPs. In the first vignette, GPSI-CVD more often considered performing electrocardiography (ECG) than other GPs (64.0% vs. 32.5%, p = 0.003). In the second vignette, GPSI-CVD were more inclined to perform both ECG (36.0% vs. 12.2%, p = 0.003) and natriuretic peptide testing (56.0% vs. 32.5%, p = 0.006).ConclusionsMost GPs seemed to consider multiple diagnoses, including HF, with GPSI-CVD more likely performing ECG and natriuretic peptide testing in an older male person with both respiratory and suggestive HF symptoms.

Patient Navigation for Lung Cancer Screening at a Health Care for the Homeless Program

People experiencing homelessness die of lung cancer at rates more than double those in the general population. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality, but the circumstances of homelessness create barriers to LCS participation. To determine whether patient navigation, added to usual care, improved LCS LDCT receipt at a large Health Care for the Homeless (HCH) program. This parallel group, pragmatic, mixed-methods randomized clinical trial was conducted at Boston Health Care for the Homeless Program (BHCHP), a federally qualified HCH program that provides tailored, multidisciplinary care to nearly 10 000 homeless-experienced patients annually. Eligible individuals had a lifetime history of homelessness, had a BHCHP primary care practitioner (PCP), were proficient in English, and met the pre-2022 Medicare coverage criteria for LCS (aged 55-77 years, ≥30 pack-year history of smoking, and smoking within the past 15 years). The study was conducted between November 20, 2020, and March 29, 2023. Participants were randomized 2:1 to usual BHCHP care either with or without patient navigation. Following a theory-based, patient-centered protocol, the navigator provided lung cancer education, facilitated LCS shared decision-making visits with PCPs, assisted participants in making and attending LCS LDCT appointments, arranged follow-up when needed, and offered tobacco cessation support for current smokers. The primary outcome was receipt of a 1-time LCS LDCT within 6 months after randomization, with between-group differences assessed by χ2 analysis. Qualitative interviews assessed the perceptions of participants and PCPs about the navigation intervention. In all, 260 participants (mean [SD] age, 60.5 [4.7] years; 184 males [70.8%]; 96 non-Hispanic Black participants [36.9%] and 96 non-Hispanic White participants [36.9%]) were randomly assigned to usual care with (n = 173) or without (n = 87) patient navigation. At 6 months after randomization, 75 participants in the patient navigation arm (43.4%) and 8 of those in the usual care-only arm (9.2%) had completed LCS LDCT (P < .001), representing a 4.7-fold difference. Interviews with participants in the patient navigation arm and PCPs identified key elements of the intervention: multidimensional social support provision, care coordination activities, and interpersonal skills of the navigator. In this randomized clinical trial, patient navigation support produced a 4.7-fold increase in 1-time LCS LDCT completion among HCH patients in Boston. Future work should focus on longer-term screening participation and outcomes. ClinicalTrials.gov Identifier: NCT04308226.

Biomarker-driven radiation therapy dose reduction after transoral robotic surgery for the treatment of HPV-positive oropharyngeal cancer.

TPS6119 Background: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is a highly curable cancer with a considerable burden of treatment-related toxicities. Transoral surgery (TOS) is a treatment option for patients with early-stage disease; however, adjuvant radiotherapy (RT) is often recommended and can add to these late toxicities. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive marker of tumor recurrence, and undetectable post-operative ctHPVDNA is associated with improved recurrence-free survival. We hypothesize that patients with undetectable post-TOS ctHPVDNA without high risk pathologic factors can safely undergo de-escalation of adjuvant RT to 36 Gy, and this reduction will improve long-term swallowing function. Methods: We opened a multi-institutional phase II study (NCT05387915) including patients with pT1-2, N0-1, M0 HPV-related OPSCC who had TOS resection of their primary site and at least ipsilateral neck dissection. Pertinent inclusion criteria include a &lt;10 pack-year smoking history, or a &lt;30 pack-year smoking history if &gt;10 years since last tobacco consumption, and pathologic findings of one or more intermediate risk factors: close margin (1 – 4 mm), perineural invasion, 2 – 4 positive lymph nodes or a single lymph node &gt;3 cm. Patients with high risk factors (positive margin, extranodal extension, 5 or more positive lymph nodes) are excluded. Patients must have a detectable pre-operative ctHPVDNA and a post-operative ctHPVDNA drawn 7-14 days after TOS; if negative, patients receive 36 Gy of adjuvant RT in 15 fractions of 2.4 Gy delivered daily; if positive, they receive care per the discretion of the treating radiation oncologist. If the final surgical margins at the site of the primary tumor are &gt;2mm, patients are eligible for omission of the primary tumor post-operative bed from the radiation volume. Our primary endpoint is 1-year swallowing function as measured by the composite MD Anderson Dysphagia Index (MDADI) score. Secondary endpoints include overall/progression-free survival and other quality of life metrics. The study is powered to detect an 8.5-point improvement in MDADI composite score at one year over the historical control from ECOG 3311 Arm B. With an alpha of 0.05 and a power of 0.90 we require 27 evaluable patients. Accounting for dropout and patients lost to follow-up, we aim to enroll 35 total patients. Since accrual began in June 2022, we have enrolled 18 patients as of January 2024. We recently opened the study at a second institution and are in the process of opening at a third institution. Clinical trial information: NCT05387915 .

Can TTMV clearance predict recurrence in HPV HNSCC?

6066 Background: Patients with locally advanced (LA) HPV HNSCC are treated with various types of induction chemotherapy (IC) followed by standard (sd) or reduced (rd) chemoradiation (CRT). Tumor tissue-modified viral HPV DNA (TTMV) pairs with PET-CT in predicting an early detection of treatment failure in HPV-related HNSCC. Mid-treatment TTMV assessment in HPV-related HNSCC can help identify patients who are eligible to receive a lower dose of IC and/or CRT or those who may require close follow-up. Methods: Patients with LA HPV+ HNSCC with high-risk features (radiographic ECE, T4 primary, &gt;N2c) and &lt;20 pack-year (py) smoking history were treated with IC followed by rdCRT (56 Gy); sdCRT (70 Gy) was used in non-responders. 16/23 received IC with TPF, 1/23 TP, and 6/23 TP-PD1, and all patients received carboplatin weekly with their CRT. Regeneron trial patients who received TP-Cemiplimab (PD1) IC followed by sdCRT are also continuing adjuvant Cemiplimab alone for 6 months (NCT05376553). PET-CT-confirmed residual, recurrent, or metastatic diseases were defined as treatment failures; TTMV + patients only if PET-CT confirmed. Results: 23 subjects treated with IC followed by CRT between 2/4/21-1/26/24, who had pre- and post-treatment TTMV were included in our analysis. The median pre-IC TTMV was 8082 (27 – 90770). The median follow-up time from treatment start was 21 months. 9/23 patients had full clearance TTMV after 1 cycle of IC defined as rapid responders (RR). 11/23 patients still had positive TTMV after 1st cycle of IC were defined as slow responders (SR). 1 patient had no TTMV done after 1 cycle of IC but was elevated after 2nd IC; he was defined as SR. 2 patients had a positive pre-IC TTMV, but no TTMV was drawn during IC to see if RR. 1 of 2 patients was TTMV negative prior to CRT, and 2/2 had a 1st post IC negative TTMV done 1 week after CRT started. They were both included in the analysis but defined as unknown response status. TTMV testing was done for all 23 subjects after CRT; all were negative. All subjects have TTMV testing done during their surveillance visits. Among 9/23 RR, none developed a failure. Among 12/23 SR, 3 patients developed a failure: 1/3 was TTMV+ but PET-, being followed with TTMV and PET-CT; and 2/3 were confirmed failures, TTMV+ and PET+; 1 locoregional, 1 metastatic. 2 patients were not known to be a SR or RR and had no recurrence. Among 23 patients, NPV of TTMV to detect failure was 100%, but PPV was 96% (1/23). Conclusions: IC followed in rapid clearance of TTMV in 39% of patients, and all remained disease-free. 3/11 (27%) with persistently elevated TTMV after cycle 1 relapsed as of this time point. This small study was not large enough to be practice-changing. However, this is significantly hypothesis-generating and should be tested in a larger trial to help identify patients for de-escalation (RR) or closer surveillance (SR).

Use of cell-free tumor DNA in early detection of lung cancer.

e20088 Background: USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults 50-80 years with 20 pack-year smoking history or current/former smoking in the past 15 years. This prospective study evaluated whether we could detect lung cancer at the time of LDCT screening from cell-free tumor DNA using Guardant Health’s LUNAR-2 assay. Methods: Kaiser Permanente Colorado (KPCO) members with upcoming LDCT screenings were invited via email/phone and recruited into two groups, (1) suspicious lung nodules or (2) no lung nodules. We limited enrollment to patients whose LDCT results were classified under the Lung-RADS (version 1.0) categories of 1-3 (recommended follow-up at 12-month intervals) or category 4 (“suspicious”; recommended follow-up at 3-month intervals). We excluded members with lung nodules &gt; 30mm, those with a history of any hematologic malignancy, history of invasive malignancy within the past 5 years, currently pregnant, or known dementia or cognitive impairment. After informed consent, Guardant Health LUNAR test collection kits were mailed to the participant with sample collection instructions provided. Participants were asked to have their blood drawn on the day of their LDCT visit, or no more than 14 days of the scan. We also collected survey and EHR data on smoking history, LDCT, and other associated factors. The KPCO tumor registry confirmed all reported cancers. Results: The study initiated in September 2020 and ended in 08/2022 with 982 individuals consented and blood samples collected. Participants were on average 68 years old, 56% female, 58% former smokers, and 85% had no personal history of cancer. A total of 15 lung cancer cases and 22 other cancer cases were diagnosed. Data analysis is ongoing and expected to be completed early 2024. Conclusions: This study will demonstrate sensitivity and specificity of the LUNAR-2 assay to detect lung cancer relative to standard of care screening modalities in high-risk populations. We will also evaluate whether factors such as comorbidities, pack year history, or medications affect assay accuracy. The impact of this research can inform blood-based early detection of lung cancer.

Artificial intelligence–aided lung cancer screening in routine clinical practice: A pilot of LungFlag at Geisinger.

e13604 Background: Use of low-dose computed tomography (LDCT) in lung cancer screening is recommended for early detection and can reduce mortality. LungFlag (Medial-EarlySign) is a machine-learning risk prediction model that identifies individuals at high risk of non-small cell lung cancer so their care team may recommend LDCT screening. The LungFlag model was developed using data from Kaiser Permanente Southern California and is being implemented in a pilot at Geisinger. Here we provide an overview of the clinical workflow for the LungFlag pilot. Methods: Geisinger has implemented LungFlag into routine clinical practice via integration with the electronic medical record system. This pilot is examining the performance and clinical impact of LungFlag in the first year. LungFlag runs every month to provide risk evaluation for individuals 50 to 80 years old who are eligible for annual lung cancer screening according to US Preventive Services Task Force recommendations. Eligible individuals have a 20 pack-year smoking history, no lung cancer history, and currently smoke or quit within the past 15 years. Patients with cancer history in the past 5 years and those screened or scheduled for screening in the past year are excluded. LungFlag identifies the top 30 individuals with the highest LungFlag scores per month (high-risk patients) and refers them for targeted outreach from a lung cancer screening program nurse navigator. A positive LungFlag result prompts nurse navigator chart review, patient outreach, and coordination with the primary care provider. Flagged individuals are contacted (up to 3 phone calls) and encouraged to receive lung cancer screening. Individuals not flagged by the model (non–high-risk patients) receive usual care consisting of reminders for lung cancer screening during primary care visits without additional targeted outreach and high-risk prioritization. Results: The LungFlag pilot was initiated in August 2023 and will continue until August 2024. As of January 2024, risk profiles of &gt;12,000 patients were analyzed and 180 high-risk patients were identified. Conclusions: This pilot is the first evaluation of the implementation process for the LungFlag model in routine clinical practice. After the pilot, a retrospective observational study is planned to further assess the impact of LungFlag and the associated clinical workflow in identifying high-risk individuals and increasing compliance with LDCT screening among high-risk individuals.

A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial.

AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.

Patient Lung Cancer Screening Decisions and Environmental and Psychosocial Factors

Screening for lung cancer using low-dose computed tomography is associated with reduced lung cancer-specific mortality, but uptake is low in the US; understanding how patients make decisions to engage with lung cancer screening is critical for increasing uptake. Prior research has focused on individual-level psychosocial factors, but environmental factors (eg, historical contexts that include experiencing racism) and modifying factors-those that can be changed to make it easier or harder to undergo screening-also likely affect screening decisions. To investigate environmental, psychosocial, and modifying factors influencing lung cancer screening decision-making and develop a conceptual framework depicting relationships between these factors. This multimethod qualitative study was conducted from December 2021 to June 2022 using virtual semistructured interviews and 4 focus groups (3-4 participants per group). All participants met US Preventive Services Task Force eligibility criteria for lung cancer screening (ie, age 50-80 years, at least a 20 pack-year smoking history, and either currently smoke or quit within the past 15 years). Screening-eligible US participants were recruited using an online panel. Key factors influencing screening decisions (eg, knowledge, beliefs, barriers, and facilitators) were the main outcome. A theory-informed, iterative inductive-deductive approach was applied to analyze data and develop a conceptual framework summarizing results. Among 34 total participants (interviews, 20 [59%]; focus groups, 14 [41%]), mean (SD) age was 59.1 (4.8) years and 20 (59%) identified as female. Half had a household income below $20 000 (17 [50%]). Participants emphasized historical and present-day racism as critical factors contributing to mistrust of health care practitioners and avoidance of medical procedures like screening. Participants reported that other factors, such as public transportation availability, also influenced decisions. Additionally, participants described psychosocial processes involved in decisions, such as perceived screening benefits, lung cancer risk appraisal, and fear of a cancer diagnosis or harmful encounters with practitioners. In addition, participants identified modifying factors (eg, insurance coverage) that could make receiving screening easier or harder. In this qualitative study of patient lung cancer screening decisions, environmental, psychosocial, and modifying factors influenced screening decisions. The findings suggest that systems-level interventions, such as those that help practitioners understand and discuss patients' prior negative health care experiences, are needed to promote effective screening decision-making.

Pack Years of Tobacco Cigarette Smoking as a Predictor of Bony Fusion after Anterior Cervical Discectomy and Fusion

Smoking tobacco cigarettes negatively impacts bone healing after spinal fusion. Smoking history is often assessed based on current smoker and nonsmoker status. However, in current research, smoking history has not been quantified in terms of pack years to estimate lifetime exposure and assess its effects. Our goal was to investigate the influence of smoking history, quantified in pack years, on bony fusion after anterior cervical discectomy and fusion (ACDF). A retrospective chart review of consecutive patients who underwent ACDF for cervical disc degeneration between September 21, 2017 and October 17, 2018 was conducted. Patient demographics, procedural variables, and postoperative outcomes were analyzed. Multivariate logistic regression analysis was performed to identify predictive factors for bony fusion following ACDF. Receiver operating characteristic curve analysis was used to determine the optimal discrimination threshold for smoking history pack years in association with nonfusion. Among 97 patients identified, 90 (93%) demonstrated bony fusion on postoperative imaging. Mean number of smoking history pack years was 6.1±13 for the fusion group and 16±21 for the nonfusion group. Multivariate logistic regression analysis suggested that increased pack years of tobacco cigarette smoking was a significant predictor of nonfusion (95% confidence interval, [1.0,1.1], P= 0.045). The receiver operating characteristic curve analysis revealed that 6.1 pack years best stratified the risk for nonfusion (area under the curve, 0.8). Patients with a history of tobacco cigarette smoking ≥6.1 pack years may have an increased risk of nonfusion after ACDF.

April 2024 Medical Image of the Month: Wind Instruments Player Exhibiting Exceptional Pulmonary Function

No abstract available. Manuscript truncated after 150 words. A 64-year-old man was referred to our pulmonary clinic for evaluation of his pulmonary status. He had a 7-year history of rheumatoid arthritis and was treated initially with steroids and subsequently maintained on methotrexate and monthly adalimumab injections monthly. The patient reported that his rheumatoid arthritis symptoms were controlled. He experienced no joint pain or morning stiffness at the time of evaluation. From a pulmonary perspective, he denied respiratory symptoms such as exertional shortness of breath, cough, wheezing, or chest tightness. He reported no limitations in physical activities. The patient has an occupational history of 45-years as a welder, with exposure to dust, metal fumes, benzene, and sulfur gas. The patient also has a 15 pack-year smoking history but quit 35 years ago. A high-resolution chest CT (Figure 1) ordered by his rheumatologist showed normal lung parenchyma. The first pulmonary function test (PFT), conducted on the initial pulmonary clinic visit …