Browsing by Subject "Lung neoplasms"
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Item Accuracy of Chest Computed Tomography in Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations in Children(American Medical Association, 2022-06-01) Engwall-Gill, Abigail J.; Chan, Sherwin S.; Boyd, Kevin P.; Saito, Jacqueline M.; Fallat, Mary E.; St. Peter, Shawn D.; Bolger-Theut, Stephanie; Crotty, Eric J.; Green, Jared R.; Hulett Bowling, Rebecca L.; Kumbhar, Sachin S.; Rattan, Mantosh S.; Young, Cody M.; Canner, Joseph K.; Deans, Katherine J.; Gadepalli, Samir K.; Helmrath, Michael A.; Hirschl, Ronald B.; Kabre, Rashmi; Lal, Dave R.; Landman, Matthew P.; Leys, Charles M.; Mak, Grace Z.; Minneci, Peter C.; Wright, Tiffany N.; Kunisaki, Shaun M.; Midwest Pediatric Surgery Consortium; Surgery, School of MedicineImportance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear. Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children. Design, setting, and participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020. Main outcomes and measures: Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors. Results: Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P < .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%. Conclusions and relevance: This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted.Item Association of Allostatic Load With Overall Mortality Among Patients With Metastatic Non-Small Cell Lung Cancer(American Medical Association, 2022-07-01) Obeng-Gyasi, Samilia; Li, Yaming; Carson, William E.; Reisenger, Sarah; Presley, Carolyn J.; Shields, Peter G.; Carbone, David P.; Ceppa, DuyKhanh P.; Carlos, Ruth C.; Andersen, Barbara L.; Surgery, School of MedicineImportance: Adverse social determinants of health (SDHs) (eg, poverty) are associated with poor oncologic outcomes among patients with lung cancer. However, no studies have evaluated biological correlates of adverse SDHs, operationalized as allostatic load (AL), with mortality due to lung cancer. Objective: To examine the association among AL, SDHs, and mortality among patients with metastatic non-small cell lung cancer (NSCLC). Design, setting, and participants: This cross-sectional study of an observational cohort was performed at a National Cancer Institute-designated comprehensive cancer center with data accrued from June 1, 2017, to August 31, 2019. Patients with metastatic (stage IV) NSCLC enrolled at diagnosis into a prospective observational cohort study were included in the present analysis if they had all the biomarkers to calculate an AL score (N = 143). Follow-up was completed on August 31, 2021, and data were analyzed from July 1 to September 30, 2021. Exposures: Social determinants of health. Main outcomes and measures: Overall mortality and AL. Results: A total of 143 patients met the study criteria with a median age of 63 (IQR, 55-71) years (89 men [62.2%] and 54 women [37.8%]). In terms of race and ethnicity, 1 patient (0.7%) was Asian, 7 (4.9%) were Black, 117 (81.8%) were White, 17 (11.9%) were of multiple races, and 1 (0.7%) was of other race or ethnicity. The mean (SD) AL was 2.90 (1.37). Elevated AL covaried with lower educational level (r = -0.26; P = .002), male sex (r = 0.19; P = .02), limited mobility (r = 0.19; P = .04), worsening self-care (r = 0.30; P < .001), problems engaging in usual activities (r = 0.21; P = .01), depressive symptoms (r = 0.23; P = .005), and a high number of stressful life events (r = 0.30; P < .001). Multivariable analysis found only increasing difficulty with mobility (r = 0.37 [95% CI, 0.13-0.60]; P = .002) and male sex (r = 0.63 [95% CI, 0.19-1.08]; P = .005) associated with higher AL. On adjusted analysis, elevated AL (hazard ratio, 1.43 [95% CI, 1.16-1.79]; P = .001) and low educational level (hazard ratio, 2.11 [95% CI, 1.03-4.34]; P = .04) were associated with worse overall mortality. Conclusions and relevance: The findings of this cross-sectional study suggest that higher AL was associated with adverse SDHs and worse overall mortality among patients with advanced NSCLC. These results provide a framework for replication and further studies of AL as a biological correlate for SDH and future prognostic marker.Item Defining comprehensive biomarker‐related testing and treatment practices for advanced non‐small‐cell lung cancer: Results of a survey of U.S. oncologists(Wiley, 2022) Mileham, Kathryn F.; Schenkel, Caroline; Bruinooge, Suanna S.; Freeman-Daily, Janet; Basu Roy, Upal; Moore, Amy; Smith, Robert A.; Garrett-Mayer, Elizabeth; Rosenthal, Lauren; Garon, Edward B.; Johnson, Bruce E.; Osarogiagbon, Raymond U.; Jalal, Shadia; Virani, Shamsuddin; Weber Redman, Mary; Silvestri, Gerard A.; Medicine, School of MedicineBackground: An ASCO taskforce comprised of representatives of oncology clinicians, the American Cancer Society National Lung Cancer Roundtable (NLCRT), LUNGevity, the GO2 Foundation for Lung Cancer, and the ROS1ders sought to: characterize U.S. oncologists' biomarker ordering and treatment practices for advanced non-small-cell lung cancer (NSCLC); ascertain barriers to biomarker testing; and understand the impact of delays on treatment decisions. Methods: We deployed a survey to 2374 ASCO members, targeting U.S. thoracic and general oncologists. Results: We analyzed 170 eligible responses. For non-squamous NSCLC, 97% of respondents reported ordering tests for EGFR, ALK, ROS1, and BRAF. Testing for MET, RET, and NTRK was reported to be higher among academic versus community providers and higher among thoracic oncologists than generalists. Most respondents considered 1 (46%) or 2 weeks (52%) an acceptable turnaround time, yet 37% usually waited three or more weeks to receive results. Respondents who waited ≥3 weeks were more likely to defer treatment until results were reviewed (63%). Community and generalist respondents who waited ≥3 weeks were more likely to initiate non-targeted treatment while awaiting results. Respondents <5 years out of training were more likely to cite their concerns about waiting for results as a reason for not ordering biomarker testing (42%, vs. 19% with ≥6 years of experience). Conclusions: Respondents reported high biomarker testing rates in patients with NSCLC. Treatment decisions were impacted by test turnaround time and associated with practice setting and physician specialization and experience.Item Emergency department involvement in the diagnosis of cancer among older adults: a SEER-Medicare study(Oxford University Press, 2024) Thompson, Caroline A.; Sheridan, Paige; Metwally, Eman; Peacock Hinton, Sharon; Mullins, Megan A.; Dillon, Ellis C.; Thompson, Matthew; Pettit, Nicholas; Kurian, Allison W.; Pruitt, Sandi L.; Lyratzopoulos, Georgios; Emergency Medicine, School of MedicineBackground: Internationally, 20% to 50% of cancer is diagnosed through emergency presentation, which is associated with lower survival, poor patient experience, and socioeconomic disparities, but population-based evidence about emergency diagnosis in the United States is limited. We estimated emergency department (ED) involvement in the diagnosis of cancer in a nationally representative population of older US adults, and its association with sociodemographic, clinical, and tumor characteristics. Methods: We analyzed Surveillance, Epidemiology, and End Results Program-Medicare data for Medicare beneficiaries (≥66 years old) with a diagnosis of female breast, colorectal, lung, and prostate cancers (2008-2017), defining their earliest cancer-related claim as their index date, and patients who visited the ED 0 to 30 days before their index date to have "ED involvement" in their diagnosis, with stratification as 0 to 7 or 8 to 30 days. We estimated covariate-adjusted associations of patient age, sex, race and ethnicity, marital status, comorbidity score, tumor stage, year of diagnosis, rurality, and census-tract poverty with ED involvement using modified Poisson regression. Results: Among 614 748 patients, 23% had ED involvement, with 18% visiting the ED in the 0 to 7 days before their index date. This rate varied greatly by tumor site, with breast cancer at 8%, colorectal cancer at 39%, lung cancer at 40%, and prostate cancer at 7%. In adjusted models, older age, female sex, non-Hispanic Black and Native Hawaiian or Other Pacific Islander race, being unmarried, recent year of diagnosis, later-stage disease, comorbidities, and poverty were associated with ED involvement. Conclusions: The ED may be involved in the initial identification of cancer for 1 in 5 patients. Earlier, system-level identification of cancer in non-ED settings should be prioritized, especially among underserved populations.Item Feasibility of a lung airway navigation system using fiber-Bragg shape sensing and artificial intelligence for early diagnosis of lung cancer(Public Library of Science, 2022-12-07) Gruionu, Lucian Gheorghe; Udriștoiu, Anca Loredana; Iacob , Andreea Valentina; Constantinescu, Cătălin; Stan, Răzvan; Gruionu, Gabriel; Medicine, School of MedicineCurrently early diagnosis of malignant lesions at the periphery of lung parenchyma requires guidance of the biopsy needle catheter from the bronchoscope into the smaller peripheral airways via harmful X-ray radiation. Previously, we developed an image-guided system, iMTECH which uses electromagnetic tracking and although it increases the precision of biopsy collection and minimizes the use of harmful X-ray radiation during the interventional procedures, it only traces the tip of the biopsy catheter leaving the remaining catheter untraceable in real time and therefore increasing image registration error. To address this issue, we developed a shape sensing guidance system containing a fiber-Bragg grating (FBG) catheter and an artificial intelligence (AI) software, AIrShape to track and guide the entire biopsy instrument inside the lung airways, without radiation or electromagnetic navigation. We used a FBG fiber with one central and three peripheral cores positioned at 120° from each other, an array of 25 draw tower gratings with 1cm/3nm spacing, 2 mm grating length, Ormocer-T coating, and a total outer diameter of 0.2 mm. The FBG fiber was placed in the working channel of a custom made three-lumen catheter with a tip bending mechanism (FBG catheter). The AIrShape software determines the position of the FBG catheter by superimposing its position to the lung airway center lines using an AI algorithm. The feasibility of the FBG system was tested in an anatomically accurate lung airway model and validated visually and with the iMTECH platform. The results prove a viable shape-sensing hardware and software navigation solution for flexible medical instruments to reach the peripheral airways. During future studies, the feasibility of FBG catheter will be tested in pre-clinical animal models.Item IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer(Frontiers Media, 2022-04-20) Heim, Lisanne; Yang, Zuqin; Tausche, Patrick; Hohenberger, Katja; Chiriac, Mircea T.; Koelle, Julia; Geppert, Carol-Immanuel; Kachler, Katerina; Miksch, Sarah; Graser, Anna; Friedrich, Juliane; Kharwadkar, Rakshin; Rieker, Ralf J.; Trufa, Denis I.; Sirbu, Horia; Neurath, Markus F.; Kaplan, Mark H.; Finotto, Susetta; Microbiology and Immunology, School of MedicineAlthough lung cancer is the leading cause of cancer deaths worldwide, the mechanisms how lung cancer cells evade the immune system remain incompletely understood. Here, we discovered IL-9-dependent signaling mechanisms that drive immune evasion in non-small cell lung cancer (NSCLC). We found increased IL-9 and IL-21 production by T cells in the tumoral region of the lung of patients with NSCLC, suggesting the presence of Th9 cells in the lung tumor microenvironment. Moreover, we noted IL-9 producing Tregs in NSCLC. IL-9 target cells in NSCLC consisted of IL-9R+ tumor cells and tumor-infiltrating lymphocytes. In two murine experimental models of NSCLC, and in vitro, IL-9 prevented cell death and controlled growth of lung adenocarcinoma cells. Targeted deletion of IL-9 resulted in successful lung tumor rejection in vivo associated with an induction of IL-21 and reduction of Treg cells. Finally, anti-IL-9 antibody immunotherapy resulted in suppression of tumor development even in established experimental NSCLC and was associated with reduced IL-10 production in the lung. In conclusion, our findings indicate that IL-9 drives immune escape of lung tumor cells via effects on tumor cell survival and tumor infiltrating T cells. Thus, strategies blocking IL-9 emerge as a new approach for clinical therapy of lung cancer.Item Impact of Lung Parenchymal-Only Failure on Overall Survival in Early-Stage Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy(Elsevier, 2021) Elbanna, May; Shiue, Kevin; Edwards, Donna; Cerra-Franco, Alberto; Agrawal, Namita; Hinton, Jason; Mereniuk, Todd; Huang, Christina; Ryan, Joshua L.; Smith, Jessica; Aaron, Vasantha D.; Burney, Heather; Zang, Yong; Holmes, Jordan; Langer, Mark; Zellars, Richard; Lautenschlaeger, Tim; Radiation Oncology, School of MedicineIntroduction: The impact of lung parenchymal-only failure on patient survival after stereotactic ablative body radiotherapy (SABR) for early-stage non-small-cell lung cancer (NSCLC) remains unclear. Patients and methods: The study population included 481 patients with early-stage NSCLC who were treated with 3- to 5-fraction SABR between 2000 and 2016. The primary study objective was to assess the impact of out-of-field lung parenchymal-only failure (OLPF) on overall survival (OS). Results: At a median follow-up of 5.9 years, the median OS was 2.7 years for all patients. Patients with OLPF did not have a significantly different OS compared to patients without failure (P = .0952, median OS 4.1 years with failure vs. 2.6 years never failure). Analysis in a 1:1 propensity score-matched cohort for Karnofsky performance status, comorbidity score, and smoking status showed no differences in OS between patients without failure and those with OLPF (P = .8). In subgroup analyses exploring the impact of time of failure on OS, patients with OLPF 6 months or more after diagnosis did not have significantly different OS compared to those without failure, when accounting for immortal time bias (P = .3, median OS 4.3 years vs. 3.5 years never failure). Only 7 patients in our data set experienced failure within 6 months of treatment, of which only 4 were confirmed to be true failures; therefore, limited data are available in our cohort on the impact of OLPF for ≤ 6 months on OS. Conclusion: OLPF after SABR for early-stage NSCLC does not appear to adversely affect OS, especially if occurring at least 6 months after SABR. More studies are needed to understand if OLPF within 6 months of SABR is associated with adverse OS. These data are useful when discussing prognosis of lung parenchymal failures after initial SABR.Item Impact of smoke-free ordinance strength on smoking prevalence and lung cancer incidence(PLOS, 2021-04-16) Nguyen, Ryan H.; Vater, Laura B.; Timsina, Lava R.; Durm, Gregory A.; Rupp, Katelin; Wright, Keylee; Spitznagle, Miranda H.; Paul, Brandy; Jalal, Shadia I.; Carter-Harris, Lisa; Hudmon, Karen S.; Hanna, Nasser H.; Loehrer, Patrick J.; Ceppa, DuyKhanh P.; Surgery, School of MedicineBackground: Smoke-free ordinances (SFO) have been shown to be effective public health interventions, but there is limited data on the impact SFO on lung cancer outcomes. We explored the effect of county-level SFO strength with smoking prevalence and lung cancer incidence in Indiana. Methods: We obtained county-level lung cancer incidence from the Indiana State Cancer Registry and county-level characteristics from the Indiana Tobacco Prevention and Cessation Commission's policy database between 1995 and 2016. Using generalized estimating equations, we performed multivariable analyses of smoking prevalence and age-adjusted lung cancer rates with respect to the strength of smoke-free ordinances at the county level over time. Results: Of Indiana's 92 counties, 24 had a SFO by 2011. In 2012, Indiana enacted a state-wide SFO enforcing at least moderate level SFO protection. Mean age-adjusted lung cancer incidence per year was 76.8 per 100,000 population and mean smoking prevalence per year was 25% during the study period. Counties with comprehensive or moderate SFO had a smoking prevalence 1.2% (95% CI [-1.88, -0.52]) lower compared with counties with weak or no SFO. Counties that had comprehensive or moderate SFO also had an 8.4 (95% CI [-11.5, -5.3]) decrease in new lung cancer diagnosis per 100,000 population per year compared with counties that had weak or no SFO. Conclusion: Counties with stronger smoke-free air ordinances were associated with decreased smoking prevalence and fewer new lung cancer cases per year. Strengthening SFO is paramount to decreasing lung cancer incidence.Item Low Rates of Lung and Colorectal Cancer Screening Uptake Among a Safety-net Emergency Department Population(Department of Emergency Medicine, School of Medicine, University of California, Irvine, 2022-08-11) Pettit, Nicholas; Ceppa, DuyKhanh; Monahan, Patrick; Emergency Medicine, School of MedicineIntroduction: A suspected diagnosis of cancer through an emergency department (ED) visit is associated with poor clinical outcomes. The purpose of this study was to explore the rate at which ED patients attend cancer screenings for lung, colorectal (CRC), and breast cancers based on national guidelines set forth by the United States Preventive Services Task Force (USPSTF). Methods: This was a prospective cohort study. Patients were randomly approached in the Eskenazi Hospital ED between August 2019-February 2020 and were surveyed to determine whether they would be eligible and had attended lung, CRC, and breast cancer screenings, as well as their awareness of lung cancer screening with low-dose computed tomography (LDCT). Patients who were English-speaking and ≥18 years old, and who were not critically ill or intoxicated or being seen for acute decompensated psychiatric illness were offered enrollment. Enrolled subjects were surveyed to determine eligibility for lung, colorectal, and breast cancer screenings based on guidelines set by the USPSTF. No cancer screenings were actually done during the ED visit. Results: A total of 500 patients were enrolled in this study. More participants were female (54.4%), and a majority were Black (53.0%). Most participants had both insurance (80.2%) and access to primary care (62.8%). Among the entire cohort, 63.0% identified as smokers, and 62.2% (140/225) of the 50- to 80-year-old participants qualified for lung cancer screening. No patients were screened for lung cancer in this cohort (0/225). Only 0.6% (3/500) were aware that LDCT was the preferred method for screening. Based on pack years, 35.5% (32/90) of the patients who were 40-49 years old and 6.7% (6/90) of those 30-39 years old would eventually qualify for screening. Regarding CRC screening, 43.6% (218/500) of the entire cohort was eligible. However, of those patients only 54% (118/218) had been screened. Comparatively, 77.7% (87/112) of the eligible females had been screened for breast cancer, but only 54.5% (61/112) had been screened in the prior two years. Conclusion: Many ED patients are not screened for lung/colorectal/breast cancers even though many are eligible and have reported access to primary care. This study demonstrates an opportunity and a need to address cancer screening in the ED.Item Lysosomal acid lipase, CSF1R, and PD-L1 determine functions of CD11c+ myeloid-derived suppressor cells(The American Society for Clinical Investigation, 2022-09-08) Zhao, Ting; Liu, Sheng; Ding, Xinchun; Johnson, Erica M.; Hanna, Nasser H.; Singh, Kanhaiya; Sen, Chandan K.; Wan, Jun; Du, Hong; Yan, Cong; Pathology and Laboratory Medicine, School of MedicineLysosomal acid lipase (LAL) is a key enzyme in the metabolic pathway of neutral lipids. In the blood of LAL-deficient (Lal-/-) mice, increased CD11c+ cells were accompanied by upregulated programmed cell death ligand 1 (PD-L1) expression. Single-cell RNA sequencing of Lal-/- CD11c+ cells identified 2 distinctive clusters with a major metabolic shift toward glucose utilization and reactive oxygen species overproduction. Pharmacologically blocking pyruvate dehydrogenase in glycolysis not only reduced CD11c+ cells and their PD-L1 expression but also reversed their capabilities of T cell suppression and tumor growth stimulation. Colony-stimulating factor 1 receptor (CSF1R) played an essential role in controlling Lal-/- CD11c+ cell homeostasis and function and PD-L1 expression. Pharmacological inhibition of LAL activity increased CD11c, PD-L1, and CSF1R levels in both normal murine myeloid cells and human blood cells. Tumor-bearing mice and human patients with non-small cell lung cancer also showed CD11c+ cell expansion with PD-L1 and CSF1R upregulation and immunosuppression. There were positive correlations among CD11c, PD-L1, and CSF1R expression and negative correlations with LAL expression in patients with lung cancer or melanoma using The Cancer Genome Atlas database and patient samples. Therefore, CD11c+ cells switched their functions to immune suppression and tumor growth stimulation through CSF1R/PD-L1 upregulation and metabolic reprogramming.