scholarly journals Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3450
Author(s):  
Ana Sofia Carvalho ◽  
Maria Carolina Strano Moraes ◽  
Chan Hyun Na ◽  
Ivo Fierro-Monti ◽  
Andreia Henriques ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bronchoalveolar Lavage ◽  
Smoking Status ◽  
Principal Component ◽  
Fibroblast Cell ◽  
Extracellular Vesicle ◽  
Advanced Lung Cancer ◽  
P Value ◽  
Proteomics Data

Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.

Association between digoxin use and sudden cardiac death in individuals with the rs10494366 variant of the NOS1AP gene

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Soroush ◽  
A Aarnoudse ◽  
F Shokri ◽  
M Van Den Berg ◽  
F Ahmadizar ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Smoking Status ◽  
Adaptor Protein ◽  
Therapeutic Window ◽  
P Value ◽  
Qtc Interval ◽  
Total Study Population ◽  
Increased Risk

Abstract Background Digoxin is one of the oldest cardiovascular medications still used to treat heart failure and atrial fibrillation. Due to its narrow therapeutic window, it is associated with life threatening intoxication and arrhythmias, and with QTc-shortening. Common genetic variation in the nitric oxide synthase-1 adaptor protein (NOS1AP) has been associated with QTc interval prolongation. Purpose We investigated whether the rs10494366 variant of the NOS1AP gene modified the risk of SCD in patients using digoxin. Methods In a prospective population-based cohort study, we included data of the three cohorts, started as of January 1st, 1991 until January 1st 2014. Digoxin current use on the date of cardiac death in cases and the same day of follow-up in the remainder of the cohort was a time-dependent exposure. The main outcome was SCD defined as sudden and unexpected death as a result of cardiac causes, according to international criteria. Identification and adjudication of SCD was performed independently, before the start of this study. We used Cox proportional hazard regression analysis to investigate the associations between NOS1AP rs10494366 variant and incident SCD among digoxin users compared to non-users. Associations were adjusted for age, sex (model 1) in addition to BMI, prevalent diabetes, myocardial infarction, baseline hypertension and smoking status (past, current, never) (model 2). Results We included 14,594 individuals, with a mean age of 65.3 (SD 10.3) years. Almost 59% were female. The cumulative incidence of SCD was 9.5% (609 cases) by the end of follow up. Among them, 98 (16%) individuals were exposed to digoxin at the time of death. In model 1, NOS1AP rs10494366 variant was not associated with SCD in the total study population. However, an interaction term of the gene with the daily dose of digoxin was significantly associated with increased risk of SCD (p-value 0.0001). In model 2, the risk of SCD in current users of digoxin was 4.2 [95% CI 1.3–13.8] for the GG genotype; 2.1 [95% CI 1.1–4.2] for the GT genotype, and 1.5 [95% CI 0.7–3.2] for the TT genotype. Conclusion NOS1AP rs10494366 variant modified the risk of sudden cardiac death in users of digoxin. Our study suggests that individuals with the homozygous minor GG allele have a fourfold increased risk of sudden cardiac death. Funding Acknowledgement Type of funding source: None

Overall survival in patients with lung cancer using a web-application-guided follow-up compared to standard modalities: Results of phase III randomized trial.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA9006-LBA9006 ◽  
Author(s):  
Fabrice Denis ◽  
Claire Lethrosne ◽  
Nicolas Pourel ◽  
Olivier Molinier ◽  
Yoann Pointreau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Supportive Care ◽  
Cancer Patients ◽  
Web Application ◽  
Phase Iii ◽  
P Value ◽  
Lung Cancer Patients

LBA9006 Background: We developed a web-application for an early detection of symptomatic relapse, complications and early supportive care in high-risk lung cancer patients between visits. A dynamical analysis of the weekly self-reported symptoms automatically triggered physician visit. Methods: We performed a national multi-institutional phase 3 prospective randomized study to compare web-application follow-up (experimental arm) for which patient’s self-scored symptoms that were weekly sent (between planned visits) to the oncologist and a clinical routine assessment with a CT-scan (every 3-6 months or at investigator’s discretion - standard arm). High risk lung cancer patients without progression and with a 0-2 performance status (PS) after an initial treatment were included. Maintenance chemotherapy or TKI therapy were allowed. In the experimental arm, an email alert was sent to the oncologist when some predefined clinical criteria were fulfilled: an imaging was then quickly prescribed. Early supportive cares were provided if adequate. The primary endpoint was to detect an improvement of 12% in 9 months survival in favor of the experimental arm (α = 5%, β = 20%, unilateral test). The boundary for declaring superiority with respect to overall survival at the pre-planned interim analysis was a p-value of less than 0.006. The PS at relapse, the quality of life (QOL) and cost-effectiveness were also investigated. Results: 121 patients were included in the intent-to-test survival analysis (90% were stage III/IV, median age: 65 y): 60 (61) in the experimental (standard) arms with equivalent baseline characteristics. Median follow-up was 9 months. Median overall survival in months was 19 (11.8), p=0.0014 (n  =  121; HR  =  0.33; 95 % CI, 0.16-0.67) and the PS at the first relapse was 0-1 for 81.5% (35.3%) of the patients (p<0.001) in the experimental (standard) arm. Conclusions: This trial shows a significant survival improvement using Web-application-guided follow-up that allowed better PS at relapse, earlier supportive care and reduction of routine imaging. QOL and cost analysis results will be presented during the meeting. Clinical trial information: NCT02361099.

LuCaS (Lung Cancer Surveillance) study: Surveillance models for advanced lung cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20546-e20546
Author(s):  
Sarah Anne Fraser
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Health Care ◽  
Cancer Patients ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Lung Cancer Patients

e20546 I hope to present the trial protocol as a poster at ASCO with co design work commencing 2017. Background: Lung cancer is the leading cause of cancer death in NZ.1 85% of registrations annually are stage four at diagnosis, presenting a significant burden on resources. Despite novel therapies, survival is poor and quality of life is a key consideration in patient management .2,3 Currently the aim of surveillance is to detect for disease progression and follows a three monthly pattern. There is little literature around benefits of surveillance on survival, and quality of life in these patients. 4-6 Alternative approaches to surveillance should be evaluated to ensure safe, convenient, economical care. Lung cancer outcomes for Maori patients sit significantly lower than those for New Zealand Europeans. Maori patients are twice as likely to present with locally advanced disease and four times less likely to receive curative treatment (multivariate analysis). There are significant barriers for Maori patients to attending health care including time off work, health literacy, costs, child care, language barriers, and transport. 19 Ministry of Health data describes poor outcomes for Maori lung cancer patients with rate of death sitting at 3.4 times that of non-Maori. Co-Primary End Points To determine if there is a reduction in health services utilisation (ED visits, hospital visits, unplanned clinic visits, GP visits, and Nurse Specialist contact) with the end point identified at progression, lost to follow up, or death. To compare the impact of a novel virtual surveillance model (VSM) versus usual follow-up care on patient anxiety measured using the HADS-A tool. Methods: LuCaS is a Randomised Controlled trial in patients with advanced lung cancer randomised to virtual model or standard care. Results: recruitment begins this year. Conclusions: Hypothesis:A virtual follow up model for advanced stage non-small cell lung cancer patients, extensive stage small cell lung cancer patients, and mesothelioma patients will reduce health care utilisation and patient experienced anxiety defined by reduction in Hospital Anxiety and Depression Scale (HADS-A) score, while maintaining effectiveness detecting recurrence and survival.

Lung cancer as a subsequent neoplasm: A report from the Childhood Cancer Survivor Study (CCSS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10551-10551
Author(s):  
Taumoha Ghosh ◽  
Yan Chen ◽  
Andrew C Dietz ◽  
Gregory T. Armstrong ◽  
Rebecca M. Howell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Childhood Cancer ◽  
Smoking Status ◽  
Univariate Analysis ◽  
Bone Cancer ◽  
Age At Diagnosis ◽  
Field Size ◽  
P Value ◽  
Increased Risk

10551 Background: Lung cancer has been reported as a subsequent neoplasm (SN) in childhood cancer survivors. We aimed to assess the prevalence of and risk factors for lung cancer in the CCSS. Methods: Among 25,654 five-year survivors participating in the CCSS, lung cancer was self-reported and then confirmed by pathologic record review. Cancer treatment exposures were evaluated including chemotherapy and chest radiation by field size (none, small, large) and in a dose group (0-10 Gy, 10-30 Gy, 30-40 Gy, and > 40 Gy). Standardized incidence ratios (SIR) were calculated using rates from the Surveillance, Epidemiology, and End Results program. Hazard ratios (HR) were estimated for demographic and treatment variables using Cox proportional-hazards models. Results: Forty-two survivors developed subsequent malignant lung cancer (SIR 4.0, 95% CI 2.9-5.4), including 25 carcinomas, 7 mesotheliomas and 10 others. Two additional benign neoplasms were also identified. The cumulative incidence of lung SNs was 0.18% at 30 years (95% CI 0.10-0.25). Median time from primary diagnosis was 28 years (range 11-46); median age at diagnosis was 45 years of age (range 15-65). A multivariable model, including all covariates with a p-value < 0.2 in univariate analysis, showed significant associations between lung cancer and older age at diagnosis (HR 10.5, 95% CI 1.4-76.4, for 15-21 years vs. 0-4 years), as well as with primary diagnoses (relative to leukemia, HR 8.7, 95% CI 1.1-66.0, for Hodgkin lymphoma; HR 20.7, 95% CI 1.3-331.0 for neuroblastoma; and HR 21.4, 95% CI 2.3-202.7, for bone cancer). In a treatment model, maximum chest radiation dose (HR 4.1, 95% CI 1.4-11.7, for 30-40 Gy; and HR 8.1, 95% CI 3.0-22.2, for > 40 Gy, relative to 0-10Gy), but not sex, smoking status, or chemotherapy exposures, was associated with lung cancer. Notably, six survivors who developed lung cancer received no radiation and of these, five had a primary bone cancer. At the end of follow-up, 65.9% of survivors with lung cancer were deceased vs. 14.1% of survivors without lung cancer ( p < 0.001). Conclusions: Survivors of childhood cancer are at increased risk for developing lung cancer associated with exposure to high doses of chest radiotherapy. To our knowledge, this is the first study to describe associations with neuroblastoma and bone cancer. Future studies to understand additional treatment-related risk factors beyond chest radiotherapy dose are needed.

Blood-based gene expression profiling to reveal potential response biomarkers for immunotherapy in advanced lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15155-e15155
Author(s):  
Jie Wu ◽  
Weihua Huang ◽  
Changhong Yin ◽  
Yee Him Cheung ◽  
Debra Abrams ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Time Course ◽  
Γδ T Cells ◽  
Principal Component ◽  
Genetic Mutation ◽  
Differentially Expressed ◽  
Advanced Lung Cancer

e15155 Background: Novel immunotherapies are becoming a viable option for advanced lung cancer treatment. High-throughput gene expression profiling (GEP) has enabled better understanding of patient responsiveness to targeted immunotherapy. However, non-invasive blood-based signatures are needed to monitor and predict response. Methods: To evaluate the predictive and prognostic role of blood-based GEP, we designed a longitudinal study by enrolling 15 patients with advanced lung cancers. A total of 65 samples were collected for RNA sequencing, ~4 blood specimens per patient, before and during anti-PD-1 treatment. We used multiple analyses, including time-course differential gene expression, principal component, lymphocyte compartment deconvolution, and genetic mutation, to search for and assess potential predictive and prognostic aspects. Results: Of 15 patients, 11 were classified as Responders (partial responders) and four were Non-Responders (one stable and three progressive diseases). Our analyses demonstrated: 1) By comparing baseline GEPs from Responders vs. Non-Responders before the first treatment, we identified potential markers (e.g., LY6E is significantly lower expressed in Responders, with Log2 Fold change = -3.44 and p = 1.83E-04) that can be used as predictors of responsiveness of the patients; 2) Immunoglobulin subunits- and T cell receptor complex-related genes were differentially expressed in Responders (DAVID analysis, p = 6.7E-3 and 2.1E-2, respectively), but not in Non-responders; 3) γδ T cells in the lymphocyte compartment were relatively increased in Responders; 4) Despite a different set of genes differentially expressed at different time points, the biggest GEP changes were at ~ week 6, after the second treatment. Additionally, we observed certain genes consistently up- or down-regulated through the whole course of treatment. Furthermore, after the first treatment, genes in the immune response pathway were regulated to different directions in Responders and Non-Responders. For example, interleukin receptor genes, such as IL18R1 and IL18RAP, and CD24 were down-regulated in Responders, but up-regulated in Non-Responders (p = 0.042, 0.023 and 0.044 respectively, t-test for the differential expression in these two groups). Conclusions: The utility of blood GEP to identify predictive and prognostic factors for precision immunotherapy is encouraging. Nevertheless, these results, predictive of the anti-PD-1 clinical response, are preliminary and need to be validated in a larger cohort.

168 Multidisciplinary follow up of patients with advanced lung cancer

Lung Cancer ◽  
2016 ◽  
Vol 91 ◽  
pp. S61
Author(s):  
Y. Saunders ◽  
J. Lynch ◽  
L. Pike ◽  
J. Dickson
Keyword(s):  
Lung Cancer ◽  
Advanced Lung Cancer

scholarly journals Utilizing Lung Cancer Risk Prediction Models to Promote Smoking Cessation: Two Randomized Controlled Trials

2016 ◽  
Vol 32 (5) ◽  
pp. 1196-1205 ◽  
Author(s):  
Frances C. Sherratt ◽  
Michael W. Marcus ◽  
Jude Robinson ◽  
John K. Field
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Randomized Controlled Trials ◽  
Risk Model ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Former Smokers

Purpose: The current project sought to examine whether delivery of lung cancer risk projections (calculated using the Liverpool Lung Project [LLP] risk model) predicted follow-up smoking status. Design: Two single-blinded randomized controlled trials. Setting: Stop Smoking Services in Liverpool (United Kingdom). Participants: Baseline current smokers (N = 297) and baseline recent former smokers (N = 216) were recruited. Intervention: Participants allocated to intervention groups were provided with personalized lung cancer risk projections, calculated using the LLP risk model. Measures: Baseline and follow-up questionnaires explored sociodemographics, smoking behavior, and lung cancer risk perceptions. Analysis: Bivariate analyses identified significant differences between randomization groups, and logistic regression models were developed to investigate the intervention effect on the outcome variables. Results: Lung cancer risk projections were not found to predict follow-up smoking status in the trial of baseline current smokers; however, they did predict follow-up smoking status in the trial of baseline recent former smokers (odds ratio: 1.91; 95% confidence interval: 1.03-3.55). Conclusion: The current study suggests that lung cancer risk projections may help maintain abstinence among individuals who have quit smoking, but the results did not provide evidence to suggest that lung cancer risk projections motivate current smokers to quit.

scholarly journals A pilot study of using smartphone application versus routine follow up for patients' care in advanced non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 5 (suppl) ◽  
pp. 9-9
Author(s):  
Naiyarat Prasongsook ◽  
Kasan Seetalarom ◽  
Siriwimon Saichaemchan ◽  
Kitipong Udomdamrongkul
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Cancer Care ◽  
Mobile Application ◽  
Advanced Nsclc ◽  
Patient Reported Outcome ◽  
P Value ◽  
Patient Reported

9 Background: Web-based patient reported outcome (PRO) improved quality of life (QoL), and overall survival (OS) in patients with advanced NSCLC who were treating with specific therapy. Lung Cancer Care application is a mobile application program that provides patients with individually tailored information on patient reported outcome. This study aims to invent a novel mobile application evaluating PRO for Thai NSCLC patients, and to evaluate the validity of mobile application. Methods: Our mobile application-based PRO was designed for monitoring quality of life. The validity of the application was tested following guidelines for translating, and validating a questionnaire. The quality of life score (FACT-L score). After the validated mobile application-based PRO, patients with advanced NSCLC were randomized to use mobile application-based PRO versus routine follow-up. The primary endpoint was quality of life (QoL). Secondary endpoint was OS. Results: Thirty-three patients with advanced NSCLC were enrolled. The mean of FACT-L score at baseline in mobile application-based PRO arm and routine follow up arm was similar (90.08 ± 5.66 vs 91.78 ± 5.26, p-value= 0.82). Patients with mobile application group had more FACT-L score at 3 months than patients with routine follow up arm (106 ± 5.97 vs 99.96 ± 5.74, p-value = 0.07). There was a trend towards increased in different mean of FACT-L score at baseline and 3 months in patients with mobile application compared to patients with routine follow up ( p-value = 0.05). The median follow-up time was 5.43 months, patients with mobile application had longer median OS than patients with routine follow up (4 months vs 2.9 months, p-value = 0.5). Conclusions: Lung Cancer Care application based on self-reported symptoms is a novel electronic device for real-time patient care monitoring. Our study results showed trend towards improved quality of life from using this novel mobile application. However, there was small samples for pilot testing, the relatively large sampling errors may reduce the statistical power needed to validate this tool.

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